Dr. Hori received his MD from Sapporo Medical University, Japan, and during that time he served as a Medical Student Research Fellow in the Department of Pharmacology. He explored the functional role of the SIRT1 gene, a longevity-associated gene, and its association with various conditions such as muscular dystrophy. He also completed a Visiting Student Research Fellowship at the Health Sciences University of Hokkaido and participated in Human Genetics projects focusing on an association between the 27-bp deletion and 538G>A mutation in the ABCC11 Gene.

After graduating from medical school, Dr. Hori completed a neurosurgery residency at National Hospital Organization Okayama Medical Center in Japan. Subsequently, he completed a Stereotactic and Functional Neurosurgery Fellowship and then a Neurosurgical Oncology and Radiosurgery Fellowship at The Cleveland Clinic. He also completed an International Neurosurgery Fellowship at Boston Children's Hospital, Harvard Medical School. In 2022, he moved to Stanford University as a postdoctoral fellow, and under the supervision of Dr. Anca Pasca, he participated in brain organoid research focusing on hypoxic brain injuries.

Since July 2023, Dr. Hori has been working as a Clinical Instructor (Neurosurgical Oncology and Radiosurgery) in the Department of Neurosurgery at Stanford under the supervision of Dr. Steven D. Chang. His clinical interests include malignant brain and spine tumors in both adult and pediatric patients. His clinical research focuses on the application of minimally invasive treatments such as laser interstitial thermal therapy, focused ultrasound, and radiosurgery to treat various neurosurgical conditions. His current lab research aims to develop an organoid model for radiation-induced brain injuries and a high-throughput screening platform to identify novel therapeutic compounds, for which he received a Clinician Educator Grant from Stanford University Maternal and Child Health Research Institute. Outside of medicine, he enjoys playing music including guitar and drums.

Clinical Focus

  • Neurological Surgery
  • Neurosurgical Oncology
  • Radiosurgery

Honors & Awards

  • Clinician Educator Grant, Stanford University Maternal and Child Health Research Institute (2023)
  • The Research Incentive Award, American College of Physicians Japan Chapter (2015)
  • JASSO’s Student of the Year 2012 Grand Prize, Japan Student Services Organization (2012)
  • Japanese Society of Anti-Aging Medicine Registration Award, Keystone Symposium on Aging and Diseases of Aging (2012)

Boards, Advisory Committees, Professional Organizations

  • Channel Administrator, Stanford Neurosurgery Channel in Cureus (2024 - Present)
  • Editor, Frontiers in Neurology (2023 - Present)
  • Editor, Frontiers in Oncology (2023 - Present)
  • Member, AANS/CNS Section on Tumors (2020 - Present)
  • Member, The Congress of Neurological Surgeons (2019 - Present)
  • Member, The Japan Neurosurgical Society (2012 - Present)
  • Member, The Molecular Biology Society of Japan (2009 - Present)
  • Reviewer, BMJ Case Reports (2022 - Present)
  • Reviewer, World Neurosurgery: X (2022 - Present)
  • Reviewer, Journal of Neuro-Oncology (2020 - Present)
  • Reviewer, Neuromodulation: Technology at the Neural Interface (2019 - Present)
  • Reviewer, Nutrition, Metabolism and Cardiovascular Diseases (2019 - Present)
  • Reviewer, European Journal of Medical Genetics (2018 - Present)
  • Reviewer, World Neurosurgery (2018 - Present)
  • Reviewer, Brain Research (2018 - Present)
  • Reviewer, Scientific Reports (2017 - Present)
  • Reviewer, Journal of Pharmacology and Experimental Therapeutics (2013 - Present)

Professional Education

  • Postdoctoral Fellow, Stanford University School of Medicine, Brain Organoids and Disease Modeling (NeoPasca Lab) (2023)
  • International Fellow, Boston Children's Hospital, Harvard Medical School, MA, Pediatric Neurosurgery Fellowship (2022)
  • Chief Clinical Fellow, Cleveland Clinic, OH, Neurosurgical Oncology and Radiosurgery Fellowship (2021)
  • Clinical Fellow, Cleveland Clinic, OH, Stereotactic and Functional Neurosurgery Fellowship (2019)
  • Resident, NHO Okayama Medical Center, Okayama University, Japan, Neurosurgical Residency (2018)
  • Intern, Asahi General Hospital, Japan, Mandatory Postgraduate Clinical Training Program (2015)
  • M.D., Sapporo Medical University, Japan (2013)
  • Medical Student Research Fellow, Sapporo Medical University, Japan, Molecular Pharmacology (Dr. Horio Lab) (2013)
  • Visiting Student Research Fellow, Health Sciences University of Hokkaido, Japan, Human Genetics (Dr. Niikawa Lab) (2011)


  • Yoshiyuki Horio, Atsushi Kuno, Yusuke Hori. "Japan Patent 5,850,503 Composition for treating muscular dystrophy", Sapporo Medical University, Feb 3, 2016

Lab Affiliations

All Publications

  • Stereotactic radiosurgery for facial nerve hemangioma: Case report and systematic review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Park, D. J., Hori, Y. S., Nernekli, K., Persad, A. R., Tayag, A., Ustrzynski, L., Emrich, S. C., Hancock, S. L., Chang, S. D. 2024; 126: 21-25


    Facial nerve hemangiomas (FNHs) are rare tumors that primarily occur near the geniculate ganglion in the temporal bone. Despite their rarity, they can cause significant facial nerve dysfunction. The optimal management approach for FNHs remains uncertain, with surgery being the mainstay but subject to debate regarding the extent of resection and preservation of the facial nerve.Systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried the PubMed/Medline (accessed on 5 March 2024) electronic database using combinations of the following search terms and words text: "geniculate ganglion hemangioma", "ganglional hemangioma", "hemangioma of the facial nerve", "facial hemangioma", and "intratemporal hemangioma".We identified a total of 30 literatures (321 patients). The most common site involved for the facial nerve hemangioma was the geniculate ganglion area followed by internal auditory canal, tympanic segment, labyrinthine segment and mastoid involvement. All patients were treated with conservative management or surgery. We report a 48-year-old female patient with HB grade 2 facial palsy and hemifacial spasm underwent SRS using Cyberknife technology. The treatment targeted the FNH in the left internal acoustic canal near the geniculate ganglion. Six months post-treatment, clinical improvement was evident, and lesion control was confirmed in a follow-up brain MRI.The rarity of FNHs contributes to the lack of consensus on optimal management. This illustrative case demonstrates the feasibility of SRS as a standalone treatment for FNHs.

    View details for DOI 10.1016/j.jocn.2024.05.023

    View details for PubMedID 38823231

  • Automatic Segmentation of Vestibular Schwannomas: A Systematic Review. World neurosurgery Nernekli, K., Persad, A. R., Hori, Y. S., Yener, U., Celtikci, E., Sahin, M. C., Sozer, A., Sozer, B., Park, D. J., Chang, S. D. 2024


    Vestibular Schwannomas (VS) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS.Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and CATS, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized.Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions.Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust, well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability.

    View details for DOI 10.1016/j.wneu.2024.04.145

    View details for PubMedID 38685346

  • Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report. Cureus Marianayagam, N. J., Paddick, I., Persad, A. R., Hori, Y. S., Maslowski, A., Thirunarayanan, I., Khanna, A. R., Park, D. J., Buch, V., Chang, S. D., Schneider, M. B., Yu, H., Weidlich, G. A., Adler, J. R. 2024; 16 (4): e57452


    Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

    View details for DOI 10.7759/cureus.57452

    View details for PubMedID 38699125

    View details for PubMedCentralID PMC11064878

  • Adjuvant Stereotactic Radiosurgery With or Without Postresection Fractionated Radiation Therapy for the Management of Clival Chordomas in Adults: An International Multicenter Case Series. Neurosurgery Bin-Alamer, O., Pikis, S., Mantziaris, G., Abdulbaki, A., Mallela, A. N., Lu, V. M., Peker, S., Samanci, Y., Nabeel, A. M., Reda, W. A., Tawadros, S. R., El-Shehaby, A. M., Abdelkarim, K., Emad Eldin, R. M., Sheehan, D., Sheehan, K., Liscak, R., Chytka, T., Tripathi, M., Madan, R., Speckter, H., Hernández, W., Barnett, G. H., Hori, Y. S., Dabhi, N., Aldakhil, S., Mathieu, D., Kondziolka, D., Bernstein, K., Wei, Z., Niranjan, A., Kersh, C. R., Lunsford, L. D., Sheehan, J. P., Abou-Al-Shaar, H. 2023


    Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects.To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group).We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT).Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died (P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group (P = .04).Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas.

    View details for DOI 10.1227/neu.0000000000002488

    View details for PubMedID 37052386

  • Occult Intraosseous Dermoid Cyst at the Nasofrontal Junction. Pediatric neurosurgery Hori, Y. S., Albanese, J. S., Meara, J. G., Proctor, M. R. 2022


    An extension of the dermoid cyst below the nasal bone has been identified in 10% of patients in a large series of nasal dermoid cysts, but these are generally easily identifiable and connected to the tract. To date, no previous reports have documented a case with intraosseous dermoid cyst which was completely hidden in the nasal bone.An 8 year-old previously healthy female was initially found to have a small pit on her nasal dorsum. The lesion developed local infection and she was initially treated with antibiotics two years prior to the current presentation. The lesion was diagnosed as a dermal sinus tract, and surgical removal was conducted at an outside hospital. In retrospect the pre-operative work-up imaging showed an occult intraosseous nasal bone extension, however, this was not appreciated at the initial surgery. She experienced repeat infections and underwent a second surgery with exploration under the nasal bones, however, the patient experienced recurrent postoperative local infections. The family presented to our institution for a second opinion. Our images interestingly illustrate the nasal dermoid cyst extending into the nasal bone at the nasofrontal junction without detectable extraosseous sub-nasal bone extension on the imaging. The patient proceeded with a third surgery for complete removal of the lesion via an extended vertical nasal incision. The nasal bones were removed in their entirety, the occult dermoid cyst with a small tract was located in the nasal bones and the undersurface of the bones were completely debrided. No intracranial extension was observed after careful investigation of the skull base. Particulate corticocancellous bone was used with fibrin sealant to reconstruct the defect. The nasal bones were then replaced. The pathology results were consistent with a dermoid cyst. The post-operative course was uncomplicated and she has not had a recurrence after the third surgery.This case, despite an exploration under the nasal bones, initially received incomplete resection and experienced multiple infections because of failure to appreciate the portion hidden in the nasal bones. Our case was successfully treated with ostectomy of nasal bones without recurrence and complications. This procedure allows unobstructed visualization of the entire cyst leading to the complete removal of the lesion. This is an instructive case to show that portions of the cyst may remain hidden and lead to recurrent infection, and complete resection with sufficient exposure of the entire lesion is needed to successfully treat this condition.

    View details for DOI 10.1159/000528440

    View details for PubMedID 36450236

  • Multifocal Subdural Hematoma in a Teenager after a Fourth Dimension Roller Coaster Ride. Pediatric neurosurgery Hori, Y. S., Gramer, R. M., Penumaka, A., Northam, W. T., See, A. P. 2022


    A 16 year-old previously healthy female went on a fourth dimension (4D) roller coaster ride 3 days prior to the current presentation. During the ride she had repetitive back and forth movements and her head jerked backwards and hit the seat. She gradually developed nausea and vomiting after the ride. The symptoms persisted and she visited her primary care physician two days prior to the presentation. A concussion was suspected, and no imaging was pursued at that time. Her nausea and vomiting further worsened, and she visited a local emergency department. A computed tomographic head scan showed subdural hematoma (SDH) including over the right convexity, the falx, and the tentorium. No skull fractures were identified. The patient was transferred to our hospital for further management. Repeat imaging confirmed stability of the SDH. Additional work-up studies including magnetic resonance angiography and blood count, prothrombin time, and partial thromboplastin time didn't reveal any apparent coagulopathy. Considering the onset of symptoms and her clinical picture, and the results of the work-up studies, the 4D roller coaster ride was suspected as an etiology of her multifocal SDH. To date, there are two reported cases of SDH in children after a roller coaster. Both cases were females who developed convexity SDH after riding a traditional roller coaster. Other reports documented adult cases, and traditionally, atrophic brain in elderly individual is known to be associated with development of SDH. The current report describes a first reported case of multifocal SDH after a ride of 4D roller coaster which occurred in a previously healthy young teenager. 4D roller coaster is a type of roller coaster that includes a "free spin" feature enabling 360 degrees rotational acceleration to the seats. This type of roller coaster has been introduced relatively recently and currently no literatures are available to suggest possible injury risks after a ride. Our report highlights a rare but possible risk of developing SDH after a 4D roller coaster ride even in the pediatric population and also a possible association between the development of multifocal SDH and multi-directional forces and rotations in a 4D roller coaster ride.

    View details for DOI 10.1159/000523780

    View details for PubMedID 35203080

  • Stereotactic radiosurgery for intracranial chordomas: an international multiinstitutional study. Journal of neurosurgery Pikis, S., Mantziaris, G., Peker, S., Samanci, Y., Nabeel, A. M., Reda, W. A., Tawadros, S. R., El-Shehaby, A. M., Abdelkarim, K., Eldin, R. M., Sheehan, D., Sheehan, K., Liscak, R., Chytka, T., Tripathi, M., Madan, R., Speckter, H., Hernández, W., Barnett, G. H., Hori, Y. S., Dabhi, N., Aldakhil, S., Mathieu, D., Kondziolka, D., Bernstein, K., Wei, Z., Niranjan, A., Kersh, C. R., Lunsford, L. D., Sheehan, J. P. 2022: 1-8


    The object of this study was to evaluate the safety, efficacy, and long-term outcomes of stereotactic radiosurgery (SRS) in the management of intracranial chordomas.This retrospective multicenter study involved consecutive patients managed with single-session SRS for an intracranial chordoma at 10 participating centers. Radiological and neurological outcomes were assessed after SRS, and predictive factors were evaluated via statistical methodology.A total of 93 patients (56 males [60.2%], mean age 44.8 years [SD 16.6]) underwent single-session SRS for intracranial chordoma. SRS was utilized as adjuvant treatment in 77 (82.8%) cases, at recurrence in 13 (14.0%) cases, and as primary treatment in 3 (3.2%) cases. The mean tumor volume was 8 cm3 (SD 7.3), and the mean prescription volume was 9.1 cm3 (SD 8.7). The mean margin and maximum radiosurgical doses utilized were 17 Gy (SD 3.6) and 34.2 Gy (SD 6.4), respectively. On multivariate analysis, treatment failure due to tumor progression (p = 0.001) was associated with an increased risk for post-SRS neurological deterioration, and a maximum dose > 29 Gy (p = 0.006) was associated with a decreased risk. A maximum dose > 29 Gy was also associated with improved local tumor control (p = 0.02), whereas the presence of neurological deficits prior to SRS (p = 0.04) and an age > 65 years at SRS (p = 0.03) were associated with worse local tumor control. The 5- and 10-year tumor progression-free survival rates were 54.7% and 34.7%, respectively. An age > 65 years at SRS (p = 0.01) was associated with decreased overall survival. The 5- and 10-year overall survival rates were 83% and 70%, respectively.SRS appears to be a safe and relatively effective adjuvant management option for intracranial chordomas. The best outcomes were obtained in younger patients without significant neurological deficits. Further well-designed studies are necessary to define the best timing for the use of SRS in the multidisciplinary management of intracranial chordomas.

    View details for DOI 10.3171/2021.12.JNS212416

    View details for PubMedID 35120328

  • Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS): a multi-institutional experience. Journal of neuro-oncology Peña Pino, I., Ma, J., Hori, Y. S., Fomchenko, E., Dusenbery, K., Reynolds, M., Wilke, C., Yuan, J., Srinivasan, E., Grabowski, M., Fecci, P., Domingo-Musibay, E., Fujioka, N., Barnett, G. H., Chang, V., Mohammadi, A. M., Chen, C. C. 2022; 156 (2): 295-306


    The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery remains an area of active investigation. Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT) followed by consolidation radiosurgery.Clinical outcomes of 20 patients with 21 histologically confirmed BMRS treated with SLA followed by consolidation SRS and > 6 months follow-up were collected retrospectively across three participating institutions.Consolidation SRS (5 Gy × 5 or 6 Gy × 5) was carried out 16-73 days (median of 26 days) post-SLA in patients with BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS decline was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n = 1) and new onset seizure (n = 1)). With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%. All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS. These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS.This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategy for BMRS.

    View details for DOI 10.1007/s11060-021-03893-6

    View details for PubMedID 35001245

  • Standalone gamma knife radiosurgery for brain metastasis of malignant peripheral nerve sheath tumor INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT Hori, Y. S., Barnett, G. H. 2021; 25
  • Spinal Cord Stimulation for Visceral Pain: Present Approaches and Future Strategies. Pain medicine (Malden, Mass.) Woodroffe, R. W., Pearson, A. C., Pearlman, A. M., Howard, M. A., Nauta, H. J., Nagel, S. J., Hori, Y. S., Machado, A. G., Almeida Frizon, L., Helland, L., Holland, M. T., Gillies, G. T., Wilson, S. 2020; 21 (10): 2298-2309


    The introduction of successful neuromodulation strategies for managing chronic visceral pain lag behind what is now treatment of choice in refractory chronic back and extremity pain for many providers in the United States and Europe. Changes in public policy and monetary support to identify nonopioid treatments for chronic pain have sparked interest in alternative options. In this review, we discuss the scope of spinal cord stimulation (SCS) for visceral pain, its limitations, and the potential role for new intradural devices of the type that we are developing in our laboratories, which may be able to overcome existing challenges.A review of the available literature relevant to this topic was performed, with particular focus on the pertinent neuroanatomy and uses of spinal cord stimulation systems in the treatment of malignant and nonmalignant gastrointestinal, genitourinary, and chronic pelvic pain.To date, there have been multiple off-label reports testing SCS for refractory gastrointestinal and genitourinary conditions. Though some findings have been favorable for these organs and systems, there is insufficient evidence to make this practice routine. The unique configuration and layout of the pelvic pain pathways may not be ideally treated using traditional SCS implantation techniques, and intradural stimulation may be a viable alternative.Despite the prevalence of visceral pain, the application of neuromodulation therapies, a standard approach for other painful conditions, has received far too little attention, despite promising outcomes from uncontrolled trials. Detailed descriptions of visceral pain pathways may offer several clues that could be used to implement devices tailored to this unique anatomy.

    View details for DOI 10.1093/pm/pnaa108

    View details for PubMedID 32719876

  • Earlier radiosurgery leads to better pain relief and less medication usage for trigeminal neuralgia patients: an international multicenter study. Journal of neurosurgery Mureb, M., Golub, D., Benjamin, C., Gurewitz, J., Strickland, B. A., Zada, G., Chang, E., Urgošík, D., Liščák, R., Warnick, R. E., Speckter, H., Eastman, S., Kaufmann, A. M., Patel, S., Feliciano, C. E., Carbini, C. H., Mathieu, D., Leduc, W., Nagel, S. J., Hori, Y. S., Hung, Y. C., Ogino, A., Faramand, A., Kano, H., Lunsford, L. D., Sheehan, J., Kondziolka, D. 2020: 1-8


    Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery.The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed.Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50-95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I-IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075).TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.

    View details for DOI 10.3171/2020.4.JNS192780

    View details for PubMedID 32619989

  • Insidious abdominal wall pseudocyst following ventriculoperitoneal shunting INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT Hori, Y. S., Sharma, A., Nagel, S. J. 2020; 19
  • Delayed obstructive hydrocephalus from intraventricular hemorrhage in a patient with concomitant deep vein thrombosis and occult cancer CHIRURGIA-ITALY Hori, Y. S., Ebisudani, Y., Aoi, M., Fukuhara, T. 2019; 32 (2): 99-101
  • Hypertensive Cerebral Hemorrhage in a Patient with Turner Syndrome Caused by Deletion in the Short Arm of the X Chromosome. Pediatric neurosurgery Hori, Y. S., Ohkura, T., Ebisudani, Y., Umakoshi, M., Ishi, M., Oda, K., Aoi, M., Inoue, T., Furujo, M., Tanaka, H., Fukuhara, T. 2018; 53 (3): 167-170


    Turner syndrome is a chromosomal disorder usually caused by complete deletion of an X chromosome, with deletion in the short arm of the X chromosome being a rare cause of the condition. Patients with Turner syndrome commonly develop hypertension, and associated vascular complications such as aortic dissection or cerebral hemorrhage have been reported. Cerebral hemorrhage in Turner syndrome is a rare complication, and only a few reports have been published. In these reports, all patients have XO karyotypes or a mosaic type as the cause of Turner syndrome, while no other Turner syndrome types have been documented. In this report, we present for the first time a patient with Turner syndrome caused by deletion in the short arm of the X chromosome who experienced hypertensive hemorrhage as a late complication.

    View details for DOI 10.1159/000485252

    View details for PubMedID 29275412

  • Subarachnoid hemorrhage from rupture of a rapidly formed aneurysm following relapse of fungal orbital apex syndrome CHIRURGIA-ITALY Hori, Y. S., Saito, T., Ebisudani, Y., Yamada, H., Akagi, Y., Aoi, M., Shinno, Y., Narai, H., Marunaka, H., Fukuhara, T. 2018; 31 (6): 264-267
  • Elevated Serum Fibrinogen Degradation Products on Admission Is a Novel Predictive Factor for Recurrence of Chronic Subdural Hematoma. World neurosurgery Hori, Y. S., Ebisudani, Y., Aoi, M., Fukuhara, T. 2018; 118: e753-e757


    Previous studies reported an association of hematologic parameters, including white blood cells, neutrophil, eosinophils, or coagulation-related factors, with prognosis in cerebrovascular disorders. However, an association of recurrence rate with serum coagulation-related factors (e.g., D-dimer or fibrinogen degradation products [FDP]) in chronic subdural hematoma (CSDH) is unclear.Ninety-two patients who experienced first-time CSDH treated with burr-hole hematoma evacuation were included in this study. Laboratory data on admission were used to divide patients into 2 groups: serum FDP >5 μg/mL or FDP ≤5 μg/mL (within normal range), based on the reference range of our institute. We retrospectively compared the recurrence rate of CSDH within 90 days after the first operation between these groups. Statistical significance was accepted at P < 0.05.Patients with an FDP greater than 5 μg/mL showed a significantly increased recurrence rate compared with those with a normal FDP (≤5 μg/mL; 27.3% vs. 10.2%, respectively; P = 0.03). Patients with an FDP greater than 5 μg/mL also showed a significantly higher recurrence rate within 30 days after the operation (15.2% vs. 3.4%, respectively; P = 0.04), but no difference in the recurrence rate at 31-90 days after the operation (12.1% vs. 6.8%, respectively; P = 0.38). In multivariable analysis, monolayer hematoma (odds ratio, 7.61; P = 0.003) and an FDP >5 μg/mL (odds ratio, 5.04; P = 0.01) were independent predictive factors for recurrence within 90 days.Elevated serum FDP on admission is a novel predictive factor for the recurrence of CSDH. These patients require careful follow-up, and recurrence within 30 days after the first operation should be considered.

    View details for DOI 10.1016/j.wneu.2018.07.039

    View details for PubMedID 30026157

  • Choroid Plexus Hyperplasia with Intractable Ascites and a Resulting Communicating Hydrocele following Shunt Operation for Hydrocephalus. Pediatric neurosurgery Hori, Y. S., Nagakita, K., Ebisudani, Y., Aoi, M., Shinno, Y., Fukuhara, T. 2018; 53 (6): 407-412


    Choroid plexus hyperplasia/papilloma and resulting hyperproduction of cerebrospinal fluid is a rare cause of hydrocephalus. In these patients, intractable ascites can occur after a ventriculoperitoneal (VP) shunting operation. However, shunt-related hydrocele is a rare complication of VP shunting. Previous reports have indicated catheter-tip migration to the scrotum as a cause of hydrocele. Here, we present the first documented case of choroid plexus hyperplasia that led to intractable ascites after shunting and a resulting hydrocele without catheter-tip migration into the scrotum.

    View details for DOI 10.1159/000492333

    View details for PubMedID 30157489

  • Primary Central Nervous System Hodgkin Lymphoma-Like Posttransplant Lymphoproliferative Disorder. World neurosurgery Hori, Y. S., Nagakita, K., Ebisudani, Y., Aoi, M., Fukuhara, T., Shinno, Y. 2018; 114: 230-234


    Posttransplant lymphoproliferative disorder (PTLD) is a rare condition occurring after organ transplantation. PTLD comprises 4 subtypes, of which Hodgkin lymphoma (HL) type and HL-like type (currently included in polymorphic type) account for only about 1%-3% of cases. Primary central nervous system PTLD is also rare; most cases are Epstein-Barr virus-positive, B-cell PTLD. To our knowledge, no case of HL-like PTLD has been documented.A 43-year-old woman who underwent kidney transplantation for IgA nephropathy 14 years previously presented to the emergency department with seizure. Gadolinium-enhanced T1-weighted magnetic resonance imaging showed a ring-enhancing mass in the left temporal lobe. Gross total removal of the tumor was performed, and pathologic examination revealed findings consistent with HL-like PTLD. The patient's immunosuppressants were subsequently reduced, and she received postoperative systemic therapy with rituximab and radiation therapy. Follow-up magnetic resonance imaging showed no signs of relapse.This represents an extremely rare case of a patient with HL-like PTLD occurring as a primary central nervous system lesion.

    View details for DOI 10.1016/j.wneu.2018.03.153

    View details for PubMedID 29609086

  • Extracranial glioblastoma diagnosed by examination of pleural effusion using the cell block technique: case report. Neurosurgical focus Hori, Y. S., Fukuhara, T., Aoi, M., Oda, K., Shinno, Y. 2018; 44 (6): E8


    Metastatic glioblastoma is a rare condition, and several studies have reported the involvement of multiple organs including the lymph nodes, liver, and lung. The lung and pleura are reportedly the most frequent sites of metastasis, and diagnosis using less invasive tools such as cytological analysis with fine needle aspiration biopsy is challenging. Cytological analysis of fluid specimens tends to be negative because of the small number of cells obtained, whereas the cell block technique reportedly has higher sensitivity because of a decrease in cellular dispersion. Herein, the authors describe a patient with a history of diffuse astrocytoma who developed intractable, progressive accumulation of pleural fluid. Initial cytological analysis of the pleural effusion obtained by thoracocentesis was negative, but reanalysis using the cell block technique revealed the presence of glioblastoma cells. This is the first report to suggest the effectiveness of the cell block technique in the diagnosis of extracranial glioblastoma using pleural effusion. In patients with a history of glioma, the presence of extremely intractable pleural effusion warrants cytological analysis of the fluid using this technique in order to initiate appropriate chemotherapy.

    View details for DOI 10.3171/2017.8.FOCUS17403

    View details for PubMedID 29852763

  • Adult-Onset Hemorrhagic Quasi-Moyamoya Disease with Unilateral Steno-occlusive Lesion in a Patient with Neurofibromatosis Type 1. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Hori, Y. S., Ebisudani, Y., Aoi, M., Fukuhara, T. 2018; 27 (5): 1423-1424


    Quasi-moyamoya disease is a condition that occurs in association with a specific underlying condition or disease such as atherosclerotic disease or neurofibromatosis type 1 (NF1). Pediatric cases are frequently reported, and an ischemic and bilateral presentation is more common than a hemorrhagic and unilateral presentation.A 39-year-old woman previously diagnosed with NF1 presented to our department with nausea and left hemiparesis. She was diagnosed with right temporal intracerebral hemorrhage by initial computed tomography. Subsequent angiography showed an occlusion of the terminal portion of the right internal carotid artery, and magnetic resonance imaging showed multiple flow voids in the right basal ganglia, suggesting quasi-moyamoya disease. The hematoma was surgically removed, and her neurological condition improved after the operation.This is the first reported case of quasi-moyamoya disease with a rare combination of characteristics, including an adult-onset, hemorrhagic presentation and a unilateral lesion in a patient previously diagnosed with NF1.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2017.11.025

    View details for PubMedID 29305273

  • Peritoneal catheter knot formation in ventriculoperitoneal shunting: an intraoperative artificial phenomenon? Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery Hori, Y. S., Ebisudani, Y., Umakoshi, M., Aoi, M., Fukuhara, T. 2018; 34 (1): 31-33


    Peritoneal catheter knot formation is a rare complication associated with ventriculoperitoneal shunting. In most reports, the knot formation was also considered to be the cause of shunt malfunction.In this study, we demonstrate the possible misinterpretation of peritoneal catheter knot formation in ventriculoperitoneal shunting. We found a knot in the peritoneal catheter intraoperatively, while no knot was noted on the abdominal X-ray taken 1 day prior to the operation. Our findings indicate that the knot had actually formed intraoperatively. This case suggests that we should not immediately conclude that a knot is the cause of shunt malfunction in such an operation.

    View details for DOI 10.1007/s00381-017-3649-x

    View details for PubMedID 29086001

  • Joint Capsule-Like Intracranial Osteochondroma Mimicking Cystic Meningioma. World neurosurgery Hori, Y. S., Ebisudani, Y., Aoi, M. 2017; 108: 985.e9-985.e11


    This report provides the first representative images of an intracranial osteochondroma with a cystic component mimicking cystic meningioma. A 40-year-old male presented at our outpatient clinic with decreased sensation in his right upper extremity. Preoperative computed tomography showed a tumor with a cystic meningioma-like appearance and prominent calcifications. On magnetic resonance imaging, calcification of the lesion was suggested by the T2-weighted image; weak enhancement was seen on the T1-weighted image. Following surgical removal of the tumor, the pathologic examination showed findings consistent with osteochondroma. Cystic meningioma is a rare tumor with a cystic component. Intracranial osteochondroma is also a rare, benign tumor that can mimic meningioma when presenting in the dural convexity. Our report describes the joint capsule-like appearance of a convex cystic osteochondroma including a calcified cap, bonelike structure, and fluid-containing intracapsular space. The tumor was evaluated by imaging and pathologic studies.

    View details for DOI 10.1016/j.wneu.2017.08.163

    View details for PubMedID 28882712

  • Fulminant Bacillus cereus septicaemia with multiple organ ischaemic/haemorrhagic complications in a patient undergoing chemotherapy for acute myelogenous leukaemia. BMJ case reports Hori, Y. S., Kodera, S., Nagai, Y., Suzuki, Y. 2017; 2017


    Bacillus cereus is a Gram-positive spore-forming rod widely found in the environment and is thought to be a frequent source of contamination. This micro-organism is reportedly a significant pathogenic agent among immunocompromised individuals. Furthermore, multiple cases of fulminant septicaemia have been reported among individuals receiving chemotherapy for acute myelogenous leukaemia. In some cases, B. cereus septicaemia was associated with multiple haemorrhages. We, herein, describe a patient with an extremely acute course of B. cereus septicaemia characterised by haemorrhage and infarction of multiple organs, which led to his death. Our findings suggest that delayed treatment of B. cereus in patients with haematologic malignancies undergoing chemotherapy may result in extremely poor outcomes; thus, immediate empirical treatment with vancomycin should be considered.

    View details for DOI 10.1136/bcr-2017-219996

    View details for PubMedID 29021140

    View details for PubMedCentralID PMC5652386

  • A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene. Human biology Hori, Y. S., Yamada, A., Matsuda, N., Ono, Y., Starenki, D., Sosonkina, N., Yoshiura, K. I., Niikawa, N., Ohta, T. 2017; 89 (4): 305-307


    A single nucleotide polymorphism in the ABCC11 gene, 538G>A (rs17822931), is known to determine human ear wax type. The G/G and G/A genotypes correspond to the wet type, while the A/A genotype corresponds to the dry type. Another earwax determinant, a 27-bp deletion (Δ27) downstream from the rs17822931 site, is a rare variant that leads to the dry phenotype. In a previous report, we found an individual with the G allele who unexpectedly showed the dry type of earwax, leading to the identification of Δ27. We also demonstrated that the Δ27 allele was present in individuals of Japanese, Thai, native North American, Andean, and Bolivian ancestry but absent in those of European and African ancestry. Here, we assessed the Δ27 allele frequency among Japanese and Ukrainian individuals and identified a novel association between the Δ27 and 538G>A mutations. The Δ27 allele frequency was 0.002 (3/1,520; one individual is heterozygous, and another is homozygous) among Japanese individuals and 0 (0/794) among Ukrainians. We also found a previously unreported homozygous genotype for both the Δ27 and A alleles. Our findings suggest that the Δ27 deletion may have occurred in an ABCC11 gene with the 538G>A mutation.

    View details for PubMedID 30047321

  • Presence of a Malignant Tumor as a Novel Predictive Factor for Repeated Recurrences of Chronic Subdural Hematoma. World neurosurgery Hori, Y. S., Aoi, M., Oda, K., Fukuhara, T. 2017; 105: 714-719


    Various risk factors for recurrence of chronic subdural hematomas (CSDHs) have been reported, including alcohol addiction and diabetes mellitus. However, the significance of malignant tumors with respect to CSDH recurrence remains unclear.We retrospectively evaluated 281 patients with a first-time CSDH from 2006 to 2016. The difference in the recurrence rate within 100 days postoperatively was compared between patients with a past or present extracranial malignant tumor and those with neither a past nor present extracranial malignant tumor at presentation. Patients in the former group were further divided into 2 subgroups: those with present tumors and those with past tumors. Statistical significance was defined as P < 0.05.A significantly greater repeated recurrence rate (>2 recurrences) was observed in patients with than without a past or present malignant tumor (8.5% vs. 1.7%, respectively; P = 0.01); no significant difference in the first recurrence rate was observed (19.1% vs. 16.2%, respectively; P = 0.63). Furthermore, patients with a present malignant tumor showed a marginally increased repeated recurrence rate than did patients with a past malignant tumor (20.0% vs. 3.1%, respectively; P = 0.053). In the multivariate analysis, a monolayer hematoma was the only risk factor for first recurrence (odds ratio, 3.16; P = 0.003), while a present malignant tumor was the only significant risk factor for repeated recurrences (odds ratio, 16.49; P = 0.002).The presence of a malignant tumor can be a novel predictive factor for repeated CSDH recurrences. Patients with malignant tumors should be carefully followed, and treatment options such as subcutaneous reservoir placement may be considered to prevent further recurrences.

    View details for DOI 10.1016/j.wneu.2017.06.043

    View details for PubMedID 28645606

  • Intrathecal Baclofen Pump Implantation for Type 2 Gaucher Disease. Pediatric neurosurgery Hori, Y. S., Fukuhara, T., Aoi, M., Ochi, M., Furujo, M. 2017; 52 (5): 331-335


    Gaucher disease (GD) is the most common type of lysosomal storage disease, with type 2 being the most severe subtype. Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD. However, as the enzymes do not cross the blood-brain barrier, ERT does not ameliorate neurological impairment in GD. Intrathecal baclofen therapy (IBT) is indicated for spastic neurological diseases, such as cerebral palsy, and studies have shown its therapeutic benefit in improving several manifestations of GD, such as scoliosis caused by muscle spasticity and respiratory function. To date, the potential benefits of IBT for treating lysosomal storage diseases such as GD have not been examined. Here we provide the first report of a patient with type 2 GD treated with IBT, and demonstrate its therapeutic benefit in ameliorating the neurological aspects of this disease.

    View details for DOI 10.1159/000479324

    View details for PubMedID 28848108

  • Eosinopenia in Children following Traumatic Intracranial Hemorrhage Is Associated with Poor Prognosis and Prolonged Hospital Admission. Pediatric neurosurgery Hori, Y. S., Fukuhara, T., Aoi, M., Namba, Y. 2016; 51 (2): 57-60


    Neutrophilia is associated with brain injury and is frequently accompanied by eosinopenia. Although eosinopenia is a poor prognostic indicator for various diseases, its significance in intracranial events has not been investigated.We retrospectively included 22 pediatric patients (≤18 years old) who experienced traumatic intracranial hemorrhage between 2002 and 2015. Patients were divided into two groups based on the presence or absence of eosinopenia on admission, i.e. the proportion of eosinophils to total white blood cells <1.0%.The mean Glasgow Coma Scale score was marginally lower in the eosinopenia group (14.1 vs. 12.0, p = 0.06). The mean Glasgow Outcome Scale-Extended (GOSE) score was significantly lower in the eosinopenia group (7.5 vs. 5.7, p = 0.02), and the mean length of hospital stay tended to be longer in patients with eosinopenia (7.8 vs. 28.4, p = 0.10). In our multivariate logistic regression analysis, eosinopenia was the only significant risk factor for poor outcome (GOSE score 1-7, OR 29.7, p = 0.03) and prolonged hospital stay (>2 weeks, OR 7.1, p = 0.047).These results demonstrate the significance of eosinopenia as a novel prognostic factor in traumatic intracranial hemorrhage in children.

    View details for DOI 10.1159/000441390

    View details for PubMedID 26636657

  • Prefectural difference in spontaneous intracerebral hemorrhage incidence in Japan analyzed with publically accessible diagnosis procedure combination data: possibilities and limitations. Epidemiology and health Fukuhara, T., Hori, Y. 2016; 38: e2016028


    Annually reported, publically accessible Diagnosis Procedure Combination (DPC) data from the Japanese government is a part of the total DPC database of the Japanese medical reimbursement system for hospitalization. Although medical issues can be evaluated with these data promptly, the applicability of these data in epidemiological analyses has not been assessed.We performed analyses using only statistical indices reported on the a government website. As a preliminary step, the prefectural consistency of spontaneous intracerebral hemorrhage (sICH) was examined with prefectural mortality over 20 years. Then the prefectural incidence of sICH for four years was calculated, utilizing publically accessible DPC data. To determine its reliability, the consistency was examined, and correlations were analyzed with three prefectural factors expected to have an effect: the elderly rate, mortality due to sICH, and the non-DPC bed rate. In addition, a comparison model between prefectures with this method was developed by analyzing other prefecture-specific factors.Prefectural mortality due to sICH and prefectural sICH incidence in the DPC database were both consistent over the years. Prefectural sICH incidence had a constant positive correlation with the elderly rate, a partial correlation with mortality due to sICH, but no correlation with the non-DPC bed rate, which is one of the major biases when utilizing the DPC database. In the comparison model, the factors of low income and alcohol consumption showed increased sICH incidence.Although careful attention to its limitations is required, publically accessible DPC data will provide insights into epidemiological issues.

    View details for DOI 10.4178/epih.e2016028

    View details for PubMedID 27384329

    View details for PubMedCentralID PMC5037357

  • Eosinopenia as a Predictive Factor of the Short-Term Risk of Mortality and Infection after Acute Cerebral Infarction. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Hori, Y. S., Kodera, S., Sato, Y., Shiojiri, T. 2016; 25 (6): 1307-12


    Eosinopenia has been shown to be a prognostic factor in bacteremia, chronic obstructive pulmonary disease, and myocardial infarction, but studies focusing on cerebral infarction are lacking.We conducted a retrospective study of 405 patients admitted to the Asahi General Hospital from June 2011 to September 2014 with a diagnosis of cerebral infarction within 24 hours after symptom onset. Differences in mortality, mortality associated with infection, and the prevalence of infection within 2 months of hospital admission were assessed between patients with and without eosinopenia at presentation.Patients with eosinopenia had a significantly higher mortality rate (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.17-5.21, P = .01), mortality associated with infection (HR 28.7, 95% CI 4.9-542.2, P <.0001), and an increased prevalence of infection (HR 1.83, 95% CI 1.12-2.89, P = .01) than patients without eosinopenia. Patients with neutrophilia and eosinopenia showed a significantly higher mortality rate than patients without neutrophilia (HR 3.15, 95% CI 1.40-6.92, P = .007), whereas patients with neutrophilia without eosinopenia showed no significant difference in mortality compared with patients without neutrophilia (HR 1.57, 95% CI .56-3.93, P = .37). Eosinopenia was a significant risk factor in 2-month mortality rate in multivariate analyses (HR 2.34, 95% CI 1.05-4.95, P = .04).Eosinopenia is a novel predictive factor for complications after acute cerebral infarction. Stroke patients with eosinopenia should be monitored carefully for infection.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2015.12.007

    View details for PubMedID 26971036

  • Chloroquine potentiates temozolomide cytotoxicity by inhibiting mitochondrial autophagy in glioma cells. Journal of neuro-oncology Hori, Y. S., Hosoda, R., Akiyama, Y., Sebori, R., Wanibuchi, M., Mikami, T., Sugino, T., Suzuki, K., Maruyama, M., Tsukamoto, M., Mikuni, N., Horio, Y., Kuno, A. 2015; 122 (1): 11-20


    Mitochondrial autophagy eliminates damaged mitochondria and decreases reactive oxygen species (ROS). The autophagy inhibitor chloroquine (CQ) potentiates temozolomide (TMZ) cytotoxicity in glioma cells, but it is not known whether CQ does this by inhibiting mitochondrial autophagy. The effects of CQ and TMZ on MitoSOX Red fluorescence, a mitochondrial ROS indicator, and cell death were examined in rat C6 glioma cells. Mitochondrial autophagy was monitored by the colocalization of MitoTracker Red fluorescence and EGFP-LC3 dots. Mitochondrial content was measured by MitoTracker Green fluorescence and immunoblotting for a mitochondrial protein. Finally, CQ's effects on tumor cells derived from a glioblastoma patient and human U87-MG glioblastoma cells were assessed. TMZ (100-1,000 μM) alone did not affect mitochondrial ROS or cell death in C6 cells, but when administered with CQ (10 μM), it increased mitochondrial ROS and cell death. Antioxidants significantly suppressed the CQ-augmented cell death in TMZ-treated cells, indicating that mitochondrial ROS were involved in this cell death. TMZ treatment reduced MitoTracker Green fluorescence and mitochondrial protein levels, and these effects were inhibited by CQ. TMZ also increased the colocalization of EGFP-LC3 dots with mitochondria, and CQ enhanced this effect. CQ potentiated TMZ-induced cytotoxicity in patient-derived glioblastoma cells as well as human U87-MG glioblastoma cells. These results suggest that CQ increases cellular ROS and augments TMZ cytotoxicity in glioma cells by inhibiting mitochondrial autophagy.

    View details for DOI 10.1007/s11060-014-1686-9

    View details for PubMedID 25528635

  • Inactive cardiac sarcoidosis with characteristic findings on cardiac MRI. BMJ case reports Hori, Y. S., Kodera, S., Oshima, H., Kanda, J. 2013; 2013

    View details for DOI 10.1136/bcr-2013-201462

    View details for PubMedID 24177462

    View details for PubMedCentralID PMC3822235

  • Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress. PloS one Hori, Y. S., Kuno, A., Hosoda, R., Horio, Y. 2013; 8 (9): e73875


    Excessive reactive oxygen species (ROS) induce apoptosis and are associated with various diseases and with aging. SIRT1 (sirtuin-1), an NAD+-dependent protein deacetylase, decreases ROS levels and participates in cell survival under oxidative stress conditions. SIRT1 modulates the transcription factors p53, a tumor suppressor and inducer of apoptosis, and the forkhead O (FOXO) family, both of which play roles for cell survival and cell death. In this study, we aimed to know which is working greatly among p53 and FOXOs transcription factors in SIRT1's cell protective functions under oxidative stress conditions. The antimycin A-induced increase in ROS levels and apoptosis was enhanced by SIRT1 inhibitors nicotinamide and splitomicin, whereas it was suppressed by a SIRT1 activator, resveratrol, and a SIRT1 cofactor, NAD+. SIRT1-siRNA abolished the effects of splitomicin and resveratrol. p53-knockdown experiment in C2C12 cells and experiment using p53-deficient HCT116 cells showed that splitomicin and resveratrol modulated apoptosis by p53-dependent and p53-independent pathways. In p53-independent cell protective pathway, we found that FOXO1, FOXO3a, and FOXO4 were involved in SOD2's upregulation by resveratrol. The knockdown of these three FOXOs by siRNAs completely abolished the SOD2 induction, ROS reduction, and anti-apoptotic function of resveratrol. Our results indicate that FOXO1, FOXO3a and FOXO4, are indispensable for SIRT1-dependent cell survival against oxidative stress, although deacetylation of p53 has also some role for cell protective function of SIRT1.

    View details for DOI 10.1371/journal.pone.0073875

    View details for PubMedID 24040102

    View details for PubMedCentralID PMC3770600

  • Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein. The Journal of biological chemistry Kuno, A., Hori, Y. S., Hosoda, R., Tanno, M., Miura, T., Shimamoto, K., Horio, Y. 2013; 288 (8): 5963-72


    Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy. Here, we show that oral administration of resveratrol, which leads to activation of an NAD(+)-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice. The pro-hypertrophic co-activator p300 protein but not p300 mRNA was up-regulated in the mdx heart, and resveratrol administration down-regulated the p300 protein level. In cultured cardiomyocytes, cardiomyocyte hypertrophy induced by the α(1)-agonist phenylephrine was inhibited by the overexpression of SIRT1 as well as resveratrol, both of which down-regulated p300 protein levels but not p300 mRNA levels. In addition, activation of atrial natriuretic peptide promoter by p300 was inhibited by SIRT1. We found that SIRT1 induced p300 down-regulation via the ubiquitin-proteasome pathway by deacetylation of lysine residues for ubiquitination. These findings indicate the pathological significance of p300 up-regulation in the dystrophic heart and indicate that SIRT1 activation has therapeutic potential for dystrophic cardiomyopathy.

    View details for DOI 10.1074/jbc.M112.392050

    View details for PubMedID 23297412

    View details for PubMedCentralID PMC3581415

  • Differential cell-protective function of two resveratrol (trans-3,5,4'-trihydroxystilbene) glucosides against oxidative stress. The Journal of pharmacology and experimental therapeutics Hosoda, R., Kuno, A., Hori, Y. S., Ohtani, K., Wakamiya, N., Oohiro, A., Hamada, H., Horio, Y. 2013; 344 (1): 124-32


    Resveratrol (trans-3,5,4'-trihydroxystilbene; RSV), a natural polyphenol, exerts a beneficial effect on health and diseases. RSV targets and activates the NAD(+)-dependent protein deacetylase SIRT1; in turn, SIRT1 induces an intracellular antioxidative mechanism by inducing mitochondrial superoxide dismutase (SOD2). Most RSV found in plants is glycosylated, and the effect of these glycosylated forms on SIRT1 has not been studied. In this study, we compared the effects of RSV and two glycosyl RSVs, resveratrol-3-O-β-d-glucoside (3G-RSV; polydatin/piceid) and resveratrol-4'-O-β-d-glucoside (4'G-RSV), at the cellular level. In oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, the antioxidant activity of 3G-RSV was comparable to that of RSV, whereas the radical-scavenging efficiency of 4'G-RSV was less than 50% of that of RSV. However, 4'G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects. RSV and 4'G-RSV, but not 3G-RSV, mitigated oxidative stress-induced cell death in C2C12 cells and primary neonatal rat cardiomyocytes. RSV and 4'G-RSV inhibited C2C12 cell proliferation, but 3G-RSV did not. RSV was found in both the intracellular and extracellular fractions of C2C12 cells that had been incubated with 4'G-RSV, indicating that 4'G-RSV was extracellularly deglycosylated to RSV, which was then taken up by the cells. C2C12 cells did not deglycosylate 3G-RSV. Our results point to 4'G-RSV as a useful RSV prodrug with high water solubility. These data also show that the in vitro antioxidative activity of these molecules did not correlate with their ability to protect cells from oxidative stress-induced apoptosis.

    View details for DOI 10.1124/jpet.112.198937

    View details for PubMedID 23042952

  • Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy. The Journal of pharmacology and experimental therapeutics Hori, Y. S., Kuno, A., Hosoda, R., Tanno, M., Miura, T., Shimamoto, K., Horio, Y. 2011; 338 (3): 784-94


    Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. We previously showed that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and activator of the NAD(+)-dependent protein deacetylase SIRT1, delays the progression of heart failure and prolongs the lifespan of δ-sarcoglycan-deficient hamsters. Because a defect of dystroglycan complex causes muscular dystrophies, and δ-sarcoglycan is a component of this complex, we hypothesized that resveratrol might be a new therapeutic tool for muscular dystrophies. Here, we examined resveratrol's effect in mdx mice, an animal model of Duchenne muscular dystrophy. mdx mice that received resveratrol in the diet for 32 weeks (4 g/kg diet) showed significantly less muscle mass loss and nonmuscle interstitial tissue in the biceps femoris compared with mdx mice fed a control diet. In the muscles of these mice, resveratrol significantly decreased oxidative damage shown by the immunostaining of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine and suppressed the up-regulation of NADPH oxidase subunits Nox4, Duox1, and p47(phox). Resveratrol also reduced the number of α-smooth muscle actin (α-SMA)(+) myofibroblast cells and endomysial fibrosis in the biceps femoris, although the infiltration of CD45(+) inflammatory cells and increase in transforming growth factor-β1 (TGF-β1) were still observed. In C2C12 myoblast cells, resveratrol pretreatment suppressed the TGF-β1-induced increase in reactive oxygen species, fibronectin production, and expression of α-SMA, and SIRT1 knockdown blocked these inhibitory effects. SIRT1 small interfering RNA also increased the expression of Nox4, p47(phox), and α-SMA in C2C12 cells. Taken together, these findings indicate that SIRT1 activation may be a useful strategy for treating muscular dystrophies.

    View details for DOI 10.1124/jpet.111.183210

    View details for PubMedID 21652783