All Publications


  • First reported use of machine vision image guided system for unstable thoracolumbar fusion: Technical case report INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT Malacon, K., Fatemi, P., Zygourakis, C. C. 2022; 30
  • Operative Versus Nonoperative Management of Unstable Spine Fractures in the Elderly: Outcomes and Mortality. Spine Malacon, K., Rangwalla, T., Wadhwa, H., Zygourakis, C. 2022

    Abstract

    STUDY DESIGN: Retrospective cohort study.OBJECTIVE: To assess outcomes and mortality in elderly patients following unstable spine fractures depending on treatment modality.SUMMARY OF BACKGROUND DATA: Operative management of unstable spine fractures in the elderly remains controversial due to increased risk of perioperative complications. Mortality rates after operative versus nonoperative treatment of these injuries have not been well-characterized.METHODS: Patients age >65 with unstable spine fractures without neurologic injury from 2015-2021 were identified from the Clinformatics Data Mart (CDM) Database. Demographics, complications, and mortality were collected. Multivariable logistic regression was used to adjust for the effect of baseline characteristics on mortality following unstable fracture diagnosis.RESULTS: Of 3,688 patients included, 1,330 (36.1%) underwent operative management and 2,358 (63.9%) nonoperative. At baseline, nonoperative patients were older, female, had higher Elixhauser comorbidity scores, and were more likely to have a cervical fracture. Operative patients had a longer length of stay in the hospital compared to nonoperative patients (9.7 vs. 7.7d; P<0.001). Although patients in the operative group had higher rates of readmission at 30-, 60-, 90-, and 120-days after diagnosis (P<0.01), they had lower mortality rates up to 5 years after injury. After adjusting for covariates, nonoperative patients had a 60% greater risk of mortality compared to operative patients (HR: 1.60 [1.40-1.78], P<0.001). After propensity score matching, operative patients age 65-85 had greater survivorship compared to their nonoperative counterparts.CONCLUSION: Elderly patients with an unstable spine fracture who undergo surgery experience lower mortality rates up to five years post diagnosis compared to patients who received nonoperative management, despite higher hospital readmission rates and an overall perioperative complication rate of 37.3%. Operating on elderly patients with unstable spine fractures may outweigh the risks and should be considered as a viable treatment option in appropriately selected patients.

    View details for DOI 10.1097/BRS.0000000000004466

    View details for PubMedID 36083602

  • Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Smith, C. J., Lintz, T., Clark, M. J., Malacon, K. E., Abiad, A., Constantino, N. J., Kim, V. J., Jo, Y. C., Alonso-Caraballo, Y., Bilbo, S. D., Chartoff, E. H. 2022; 47 (10): 1755-1763

    Abstract

    The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during typical development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show prenatal and adult behavioral deficits in opioid-exposed offspring, including impaired extinction of oxycodone-conditioned place preference in males. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to changes in neural systems and behavior.

    View details for DOI 10.1038/s41386-022-01376-4

    View details for PubMedID 35835992

    View details for PubMedCentralID PMC9372181

  • Prenatal environmental stressors impair postnatal microglia function and adult behavior in males. Cell reports Block, C. L., Eroglu, O., Mague, S. D., Smith, C. J., Ceasrine, A. M., Sriworarat, C., Blount, C., Beben, K. A., Malacon, K. E., Ndubuizu, N., Talbot, A., Gallagher, N. M., Chan Jo, Y., Nyangacha, T., Carlson, D. E., Dzirasa, K., Eroglu, C., Bilbo, S. D. 2022; 40 (5): 111161

    Abstract

    Gestational exposure to environmental toxins and socioeconomic stressors is epidemiologically linked to neurodevelopmental disorders with strong male bias, such as autism. We model these prenatal risk factors in mice by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activates the maternal immune system. Only male offspring display long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminish microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Precise inhibition of microglial phagocytosis within the anterior cingulate cortex (ACC) of wild-type (WT) mice during the same critical period mimics the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.

    View details for DOI 10.1016/j.celrep.2022.111161

    View details for PubMedID 35926455

  • Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell Fernández-Castañeda, A., Lu, P., Geraghty, A. C., Song, E., Lee, M. H., Wood, J., O'Dea, M. R., Dutton, S., Shamardani, K., Nwangwu, K., Mancusi, R., Yalçın, B., Taylor, K. R., Acosta-Alvarez, L., Malacon, K., Keough, M. B., Ni, L., Woo, P. J., Contreras-Esquivel, D., Toland, A. M., Gehlhausen, J. R., Klein, J., Takahashi, T., Silva, J., Israelow, B., Lucas, C., Mao, T., Peña-Hernández, M. A., Tabachnikova, A., Homer, R. J., Tabacof, L., Tosto-Mancuso, J., Breyman, E., Kontorovich, A., McCarthy, D., Quezado, M., Vogel, H., Hefti, M. M., Perl, D. P., Liddelow, S., Folkerth, R., Putrino, D., Nath, A., Iwasaki, A., Monje, M. 2022

    Abstract

    COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

    View details for DOI 10.1016/j.cell.2022.06.008

    View details for PubMedID 35768006

  • First reported use of real-time intraoperative computed tomography angiography image registration using the Machine-vision Image Guided Surgery system: illustrative case. Journal of neurosurgery. Case lessons Wadhwa, H., Malacon, K., Medress, Z. A., Leung, C., Sklar, M., Zygourakis, C. C. 2021; 1 (18): CASE2125

    Abstract

    Vertebral artery injury is a devastating potential complication of C1-2 posterior fusion. Intraoperative navigation can reduce the risk of neurovascular complications and improve screw placement accuracy. However, the use of intraoperative computed tomography (CT) increases radiation exposure and operative time, and it is unable to image vascular structures. The Machine-vision Image Guided Surgery (MvIGS) system uses optical topographic imaging and machine vision software to rapidly register using preoperative imaging. The authors presented the first report of intraoperative navigation with MvIGS registered using a preoperative CT angiogram (CTA) during C1-2 posterior fusion.MvIGS can register in seconds, minimizing operative time with no additional radiation exposure. Furthermore, surgeons can better adjust for abnormal vertebral artery anatomy and increase procedure safety.CTA-guided navigation generated a three-dimensional reconstruction of cervical spine anatomy that assisted surgeons during the procedure. Although further study is needed, the use of intraoperative MvIGS may reduce the risk of vertebral artery injury during C1-2 posterior fusion.

    View details for DOI 10.3171/CASE2125

    View details for PubMedID 35855470

    View details for PubMedCentralID PMC9245760

  • Internal state configures olfactory behavior and early sensory processing in Drosophila larvae SCIENCE ADVANCES Vogt, K., Zimmerman, D. M., Schlichting, M., Hernandez-Nunez, L., Qin, S., Malacon, K., Rosbash, M., Pehlevan, C., Cardona, A., Samuel, A. T. 2021; 7 (1)
  • Sex differences in microglia as a risk factor for Alzheimer's disease Sex and Gender Differences in Alzheimer's disease Delage , C., Rendina , D. N., Malacon , K. E., Tremblay , M., Bilbo , S. D. Elsevier Inc.. 2021; 1: 79-104
  • Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number BRAIN BEHAVIOR AND IMMUNITY Smith, C. J., Kingsbury, M. A., Dziabis, J. E., Hanamsagar, R., Malacon, K. E., Tran, J. N., Norris, H. A., Gulino, M., Bordt, E. A., Bilbo, S. D. 2020; 90: 332–45

    Abstract

    Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.

    View details for DOI 10.1016/j.bbi.2020.08.013

    View details for Web of Science ID 000577976900031

    View details for PubMedID 32860938

    View details for PubMedCentralID PMC7556772