Paul George, MD, PhD

All Publications

• Eye Toward Stroke Prevention: Central Retinal Artery Occlusion and Tandem Internal Carotid Artery Occlusion. Stroke Cheronis, C., Silverman, A., George, P. M. 2024

  View details for DOI 10.1161/STROKEAHA.123.045957

  View details for PubMedID 38511307

• Conductive gradient hydrogels allow spatial control of adult stem cell fate. Journal of materials chemistry. B Song, S., McConnell, K. W., Shan, D., Chen, C., Oh, B., Sun, J., Poon, A. S., George, P. M. 2024

  Abstract

  Electrical gradients are fundamental to physiological processes including cell migration, tissue formation, organ development, and response to injury and regeneration. Current electrical modulation of cells is primarily studied under a uniform electrical field. Here we demonstrate the fabrication of conductive gradient hydrogels (CGGs) that display mechanical properties and varying local electrical gradients mimicking physiological conditions. The electrically-stimulated CGGs enhanced human mesenchymal stem cell (hMSC) viability and attachment. Cells on CGGs under electrical stimulation showed a high expression of neural progenitor markers such as Nestin, GFAP, and Sox2. More importantly, CGGs showed cell differentiation toward oligodendrocyte lineage (Oligo2) in the center of the scaffold where the electric field was uniform with a greater intensity, while cells preferred neuronal lineage (NeuN) on the edge of the scaffold on a varying electric field at lower magnitude. Our data suggest that CGGs can serve as a useful platform to study the effects of electrical gradients on stem cells and potentially provide insights on developing new neural engineering applications.

  View details for DOI 10.1039/d3tb02269b

  View details for PubMedID 38291979

• Intravenous Tenecteplase and Carotid Artery Stenting in a Young Adult With Fibromuscular Dysplasia and Carotid Dissection. Stroke Alfandy, F., Dugue, R., Pulli, B., George, P. M. 2023

  View details for DOI 10.1161/STROKEAHA.123.045026

  View details for PubMedID 38152960

• Wirelessly Powered-Electrically Conductive Polymer System for Stem Cell Enhanced Stroke Recovery. Advanced electronic materials Santhanam, S., Chen, C., Oh, B., McConnell, K. W., Azadian, M. M., Patel, J. J., Gardner, E. E., Tanabe, Y., Poon, A. S., George, P. M. 2023; 9 (10)

  Abstract

  Effective stroke recovery therapeutics remain limited. Stem cell therapies have yielded promising results, but the harsh ischemic environment of the post-stroke brain reduces their therapeutic potential. Previously, we developed a conductive polymer scaffold system that enabled stem cell delivery with simultaneous electrical modulation of the cells and surrounding neural environment. This wired polymer scaffold proved efficacious in optimizing ideal conditions for stem cell mediated motor improvements in a rodent model of stroke. To further enable preclinical studies and enhance translational potential, we identified a method to improve this system by eliminating its dependence upon a tethered power source. We have herein developed a wirelessly powered, electrically conductive polymer system that eases therapeutic application and enables full mobility. As a proof of concept, we demonstrate that the wirelessly powered scaffold is able to stimulate neural stem cells in vitro, as well as in vivo in a rodent model of stroke. This system modulates the stroke microenvironment and increases the production of endogenous stem cells. In summation, this novel, wirelessly powered conductive scaffold can serve as a mobile platform for a wide variety of therapeutics involving electrical stimulation.

  View details for DOI 10.1002/aelm.202300369

  View details for PubMedID 38045756

  View details for PubMedCentralID PMC10691593

• Clinical Problem Solving: A 38-year-Old Woman With Systemic Lupus Erythematosus Presenting With Headache, Nausea, and Vomiting. The Neurohospitalist Silverman, A., Dugue, R., George, P. M. 2023; 13 (4): 394-398

  Abstract

  A 38-year-old woman with migraine headaches and systemic lupus erythematosus with recent cessation of her immunosuppressive therapy presents with prolonged headache and hypertensive emergency. Her examination is notable for a peripheral right facial palsy and stable malar rash. There are no signs of systemic infection nor systemic symptoms of a lupus flare. Initial CT head reveals bilateral hypodensities in the basal ganglia. Within 8 hours of presentation, she develops right hemiplegia and becomes encephalopathic. MRI shows multifocal acute infarcts (most notably in the left basal ganglia), enhancement of the right facial nerve, and multifocal vessel wall enhancement in the anterior and posterior circulation. We discuss the differential diagnosis, comprehensive workup, and subsequent treatment decisions in the management of this immunocompromised patient with encephalopathy, headache, and rapidly progressing focal neurologic deficits.

  View details for DOI 10.1177/19418744231182285

  View details for PubMedID 37701245

  View details for PubMedCentralID PMC10494810

• Controlling the Stem Cell Environment Via Conducting Polymer Hydrogels to Enhance Therapeutic Potential ADVANCED MATERIALS TECHNOLOGIES Santhanam, S., Feig, V. R., McConnell, K. W., Song, S., Gardner, E. E., Patel, J. J., Shan, D., Bao, Z., George, P. M. 2023

  View details for DOI 10.1002/admt.202201724

  View details for Web of Science ID 000940740700001

• Strategic Planning at NINDS: Translating Plans into Action and Outcomes. Neurology Jones, L. K., George, P. 2022

  View details for DOI 10.1212/WNL.0000000000201622

  View details for PubMedID 36257716

• Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke. Nature communications Oh, B., Santhanam, S., Azadian, M., Swaminathan, V., Lee, A. G., McConnell, K. W., Levinson, A., Song, S., Patel, J. J., Gardner, E. E., George, P. M. 2022; 13 (1): 1366

  Abstract

  Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.

  View details for DOI 10.1038/s41467-022-29017-w

  View details for PubMedID 35292643

• Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits. ACS biomaterials science & engineering Suhar, R. A., Marquardt, L. M., Song, S., Buabbas, H., Doulames, V. M., Johansson, P. K., Klett, K. C., Dewi, R. E., Enejder, A. M., Plant, G. W., George, P. M., Heilshorn, S. C. 2021; 7 (9): 4209-4220

  Abstract

  Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.

  View details for DOI 10.1021/acsbiomaterials.0c01053

  View details for PubMedID 34510904

• Electrical stimulation of human neural stem cells via conductive polymer nerve guides enhances peripheral nerve recovery. Biomaterials Song, S., McConnell, K. W., Amores, D., Levinson, A., Vogel, H., Quarta, M., Rando, T. A., George, P. M. 2021; 275: 120982

  Abstract

  Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances the efficacy of human neural progenitor cells (hNPCs) in treating a sciatic nerve transection in rats. Electrical stimulation strengthened the therapeutic potential of NPCs by upregulating gene expression of neurotrophic factors which are critical in augmenting synaptic remodeling, nerve regeneration, and myelination. Electrically-stimulated hNPC-containing CNGs are significantly more effective in improving sensory and motor functions starting at 1-2 weeks after treatment than either treatment alone. Electrophysiology and muscle assessment demonstrated successful re-innervation of the affected target muscles in this group. Furthermore, histological analysis highlighted an increased number of regenerated nerve fibers with thicker myelination in electrically-stimulated hNPC-containing CNGs. The elevated expression of tyrosine kinase receptors (Trk) receptors, known to bind to neurotrophic factors, indicated the long-lasting effect from electrical stimulation on nerve regeneration and distal nerve re-innervation. These data suggest that electrically-enhanced stem cell-based therapy provides a regenerative rehabilitative approach to promote peripheral nerve regeneration and functional recovery.

  View details for DOI 10.1016/j.biomaterials.2021.120982

  View details for PubMedID 34214785

• Conducting polymer-based granular hydrogels for injectable 3D cell scaffolds. Advanced materials technologies Feig, V. R., Santhanam, S., McConnell, K. W., Liu, K., Azadian, M., Brunel, L. G., Huang, Z., Tran, H., George, P. M., Bao, Z. 2021; 6 (6)

  Abstract

  Injectable 3D cell scaffolds possessing both electrical conductivity and native tissue-level softness would provide a platform to leverage electric fields to manipulate stem cell behavior. Granular hydrogels, which combine jamming-induced elasticity with repeatable injectability, are versatile materials to easily encapsulate cells to form injectable 3D niches. In this work, we demonstrate that electrically conductive granular hydrogels can be fabricated via a simple method involving fragmentation of a bulk hydrogel made from the conducting polymer PEDOT:PSS. These granular conductors exhibit excellent shear-thinning and self-healing behavior, as well as record-high electrical conductivity for an injectable 3D scaffold material (~10 S m-1). Their granular microstructure also enables them to easily encapsulate induced pluripotent stem cell (iPSC)-derived neural progenitor cells, which were viable for at least 5 days within the injectable gel matrices. Finally, we demonstrate gel biocompatibility with minimal observed inflammatory response when injected into a rodent brain.

  View details for DOI 10.1002/admt.202100162

  View details for PubMedID 34179344

  View details for PubMedCentralID PMC8225239

• Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Oh, B., Wu, Y. W., Swaminathan, V., Lam, V., Ding, J., George, P. M. 2021; 8 (7): 2002112

  Abstract

  The application of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine can be limited by the prolonged times required for functional human neuronal differentiation and traditional 2D culture techniques. Here, a conductive graphene scaffold (CGS) to modulate mechanical and electrical signals to promote human iPSC-derived neurons is presented. The soft CGS with cortex-like stiffness (≈3 kPa) and electrical stimulation (±800 mV/100 Hz for 1 h) incurs a fivefold improvement in the rate (14d) of generating iPSC-derived neurons over some traditional protocols, with an increase in mature cellular markers and electrophysiological characteristics. Consistent with other culture conditions, it is found that the pro-neurogenic effects of mechanical and electrical stimuli rely on RhoA/ROCK signaling and de novo ciliary neurotrophic factor (CNTF) production respectively. Thus, the CGS system creates a combined physical and continuously modifiable, electrical niche to efficiently and quickly generate iPSC-derived neurons.

  View details for DOI 10.1002/advs.202002112

  View details for PubMedID 33854874

  View details for PubMedCentralID PMC8025039

• Morphing electronics enable neuromodulation in growing tissue. Nature biotechnology Liu, Y. n., Li, J. n., Song, S. n., Kang, J. n., Tsao, Y. n., Chen, S. n., Mottni, V. n., McConnell, K. n., Xu, W. n., Zheng, Y. Q., Tok, J. B., George, P. M., Bao, Z. n. 2020

  Abstract

  Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases1-3. However, their fixed dimensions cannot accommodate rapid tissue growth4,5 and may impair development6. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications6-8. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.

  View details for DOI 10.1038/s41587-020-0495-2

  View details for PubMedID 32313193

• Single-Cell Encapsulation via Click-Chemistry Alters Production of Paracrine Factors from Neural Progenitor Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Oh, B. n., Swaminathan, V. n., Malkovskiy, A. n., Santhanam, S. n., McConnell, K. n., George, P. M. 2020; 7 (8): 1902573

  Abstract

  Extracellular matrix (ECM) properties affect multiple cellular processes such as cell survival, proliferation, and protein synthesis. Thus, a polymeric-cell delivery system with the ability to manipulate the extracellular environment can act as a fundamental regulator of cell function. Given the promise of stem cell therapeutics, a method to uniformly enhance stem cell function, in particular trophic factor release, can prove transformative in improving efficacy and increasing feasibility by reducing the total number of cells required. Herein, a click-chemistry powered 3D, single-cell encapsulation method aimed at synthesizing a polymeric coating with the optimal thickness around neural progenitor cells is introduced. Polymer encapsulation of neural stem cells significantly increases the release of neurotrophic factors such as VEGF and CNTF. Cell encapsulation with a soft extracellular polymer upregulates the ADCY8-cAMP pathway, suggesting a mechanism for the increase in paracrine factors. Hence, the described single-cell encapsulation technique can emerge as a translatable, nonviral cell modulation method and has the potential to improve stem cells' therapeutic effect.

  View details for DOI 10.1002/advs.201902573

  View details for PubMedID 32328414

  View details for PubMedCentralID PMC7175248

• Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds. Scientific reports Song, S., Amores, D., Chen, C., McConnell, K., Oh, B., Poon, A., George, P. M. 2019; 9 (1): 19565

  Abstract

  Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.

  View details for DOI 10.1038/s41598-019-56021-w

  View details for PubMedID 31863072

• Regulating Stem Cell Function with Electrical Stimulation Oh, B., Song, S., Lam, V., George, P. WILEY. 2019: S277–S278

  View details for Web of Science ID 000488891800447

• Conductive polymers to modulate the post-stroke neural environment BRAIN RESEARCH BULLETIN Oh, B., George, P. 2019; 148: 10–17

  View details for DOI 10.1016/j.brainresbull.2019.02.015

  View details for Web of Science ID 000467666900002

• Utilizing Single Cell Immune Profiling to Identify Serum-based Biomarkers for Transient Ischemic Attacks Therkelsen, K., Tsai, A., Mlynash, M., Oh, B., Eyngorn, I., Gaudilliere, B., George, P. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965901285

• Identification of New Therapeutic Pathways by Transcriptome Analysis of Electrically Stimulated-Neural Progenitor Cells After Stroke. Oh, B., Swaminathan, V., Lam, V., Levinson, A., George, P. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400250

• Engineered stem cell mimics to enhance stroke recovery BIOMATERIALS George, P. M., Oh, B., Dewi, R., Hua, T., Cai, L., Levinson, A., Liang, X., Krajina, B. A., Bliss, T. M., Heilshorn, S. C., Steinberg, G. K. 2018; 178: 63–72

  View details for DOI 10.1016/j.biomaterials.2018.06.010

  View details for Web of Science ID 000440959000006

• In vivo Electrical Stimulation of Neural Stem Cells via Conductive Polymer Scaffold Improves Endogenous Repair Mechanisms of Stroke Recovery Oh, B., Song, S., Lam, V., Levinson, A., George, P. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090802415

• Electrically Conductive Scaffold to Modulate and Deliver Stem Cells JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Oh, B., Levinson, A., Lam, V., Song, S., George, P. 2018

  View details for DOI 10.3791/57367

  View details for Web of Science ID 000444051300076

• Electrically Conductive Scaffold to Modulate and Deliver Stem Cells. Journal of visualized experiments : JoVE Oh, B., Levinson, A., Lam, V., Song, S., George, P. 2018

  Abstract

  Stem cell therapy has emerged as an exciting stroke therapeutic, but the optimal delivery method remains unclear. While the technique of microinjection has been used for decades to deliver stem cells in stroke models, this technique is limited by the lack of ability to manipulate the stem cells prior to injection. This paper details a method of using an electrically conductive polymer scaffold for stem cell delivery. Electrical stimulation of stem cells using a conductive polymer scaffold alters the stem cell's genes involved in cell survival, inflammatory response, and synaptic remodeling. After electrical preconditioning, the stem cells on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. This protocol describes a powerful technique to manipulate stem cells via a conductive polymer scaffold and creates a new tool to further develop stem cell-based therapy.

  View details for PubMedID 29708538

• Electrical preconditioning of stem cells with a conductive polymer scaffold enhances stroke recovery. Biomaterials George, P. M., Bliss, T. M., Hua, T. n., Lee, A. n., Oh, B. n., Levinson, A. n., Mehta, S. n., Sun, G. n., Steinberg, G. K. 2017; 142: 31–40

  Abstract

  Exogenous human neural progenitor cells (hNPCs) are promising stroke therapeutics, but optimal delivery conditions and exact recovery mechanisms remain elusive. To further elucidate repair processes and improve stroke outcomes, we developed an electrically conductive, polymer scaffold for hNPC delivery. Electrical stimulation of hNPCs alters their transcriptome including changes to the VEGF-A pathway and genes involved in cell survival, inflammatory response, and synaptic remodeling. In our experiments, exogenous hNPCs were electrically stimulated (electrically preconditioned) via the scaffold 1 day prior to implantation. After in vitro stimulation, hNPCs on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. Electrically preconditioned hNPCs improved functional outcomes compared to unstimulated hNPCs or hNPCs where VEGF-A was blocked during in vitro electrical preconditioning. The ability to manipulate hNPCs via a conductive scaffold creates a new approach to optimize stem cell-based therapy and determine which factors (such as VEGF-A) are essential for stroke recovery.

  View details for PubMedID 28719819

• Conductive polymer scaffolds to improve neural recovery. Neural regeneration research Song, S. n., George, P. M. 2017; 12 (12): 1976–78

  View details for PubMedID 29323032

  View details for PubMedCentralID PMC5784341

• Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies LANCET NEUROLOGY Kelly, P. J., Albers, G. W., Chatzikonstantinou, A., De Marchis, G. M., Ferrari, J., George, P., Katan, M., Knoflach, M., Kim, J. S., Li, L., Lee, E., Olivot, J., Purroy, F., Raposo, N., Rothwell, P. M., Sharma, V. K., Song, B., Tsivgoulis, G., Walsh, C., Xu, Y., Merwick, A. 2016; 15 (12): 1236-1245

  View details for Web of Science ID 000386315700019

• Inter-rater agreement analysis of the Precise Diagnostic Score for suspected transient ischemic attack. International journal of stroke Cereda, C. W., George, P. M., Inoue, M., Vora, N., Olivot, J., Schwartz, N., Lansberg, M. G., Kemp, S., Mlynash, M., Albers, G. W. 2016; 11 (1): 85-92

  Abstract

  No definitive criteria are available to confirm the diagnosis of transient ischemic attack. Inter-rater agreement between physicians regarding the diagnosis of transient ischemic attack is low, even among vascular neurologists. We developed the Precise Diagnostic Score, a diagnostic score that consists of discrete and well-defined clinical and imaging parameters, and investigated inter-rater agreement in patients with suspected transient ischemic attack.Fellowship-trained vascular neurologists, blinded to final diagnosis, independently reviewed retrospectively identical history, physical examination, routine diagnostic studies, and brain magnetic resonance imaging (diffusion and perfusion images) from consecutive patients with suspected transient ischemic attack. Each patient was rated using the 8-point Precise Diagnostic Score score, composed of a clinical score (0-4 points) and an imaging score (0-4 points). The composite Precise Diagnostic Score determines a Precise Diagnostic Score Likelihood of Brain Ischemia Scale: 0-1 = unlikely, 2 = possible, 3 = probable, 4-8 = very likely.Three raters reviewed data from 114 patients. Using Precise Diagnostic Score, all three raters scored a similar percentage of the clinical events as being "probable" or "very likely" caused by brain ischemia: 57, 55, and 58%. Agreement was high for both total Precise Diagnostic Score (intraclass correlation coefficient of 0.94) and for the Likelihood of Brain Ischemia Scale (agreement coefficient of 0.84).Compared with prior studies, inter-rater agreement for the diagnosis of transient brain ischemia appears substantially improved with the Precise Diagnostic Score scoring system. This score is the first to include specific criteria to assess the clinical relevance of diffusion-weighted imaging and perfusion lesions and supports the added value of magnetic resonance imaging for assessing patients with suspected transient ischemic attack.

  View details for DOI 10.1177/1747493015607507

  View details for PubMedID 26763024

• Novel TIA biomarkers identified by mass spectrometry-based proteomics INTERNATIONAL JOURNAL OF STROKE George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. 2015; 10 (8): 1204-1211

  Abstract

  Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

  View details for DOI 10.1111/ijs.12603

  View details for Web of Science ID 000367673700011

• Novel TIA biomarkers identified by mass spectrometry-based proteomics. International journal of stroke : official journal of the International Stroke Society George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. M. 2015; 10 (8): 1204-11

  Abstract

  Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

  View details for DOI 10.1111/ijs.12603

  View details for PubMedID 26307429

• Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments. Neuron George, P. M., Steinberg, G. K. 2015; 87 (2): 297-309

  Abstract

  Stroke remains a leading cause of death and disability in the world. Over the past few decades our understanding of the pathophysiology of stroke has increased, but greater insight is required to advance the field of stroke recovery. Clinical treatments have improved in the acute time window, but long-term therapeutics remain limited. Complex neural circuits damaged by ischemia make restoration of function after stroke difficult. New therapeutic approaches, including cell transplantation or stimulation, focus on reestablishing these circuits through multiple mechanisms to improve circuit plasticity and remodeling. Other research targets intact networks to compensate for damaged regions. This review highlights several important mechanisms of stroke injury and describes emerging therapies aimed at improving clinical outcomes.

  View details for DOI 10.1016/j.neuron.2015.05.041

  View details for PubMedID 26182415

• Beneficial effects of a semi-intensive stroke unit are beyond the monitor. Cerebrovascular diseases Cereda, C. W., George, P. M., Pelloni, L. S., Gandolfi-Decristophoris, P., Mlynash, M., Biancon Montaperto, L., Limoni, C., Stojanova, V., Malacrida, R., Städler, C., Bassetti, C. L. 2015; 39 (2): 102-109

  Abstract

  Precise mechanisms underlying the effectiveness of the stroke unit (SU) are not fully established. Studies that compare monitored stroke units (semi-intensive type, SI-SU) versus an intensive care unit (ICU)-based mobile stroke team (MST-ICU) are lacking. Although inequalities in access to stroke unit care are globally improving, acute stroke patients may be admitted to Intensive Care Units for monitoring and followed by a mobile stroke team in hospital's lacking an SU with continuous cardiovascular monitoring. We aimed at comparing the stroke outcome between SI-SU and MST-ICU and hypothesized that the benefits of SI-SU are driven by additional elements other than cardiovascular monitoring, which is equally offered in both care systems.In a single-center setting, we compared the unfavorable outcomes (dependency and mortality) at 3 months in consecutive patients with ischemic stroke or spontaneous intracerebral hemorrhage admitted to a stroke unit with semi-intensive monitoring (SI-SU) to a cohort of stroke patients hospitalized in an ICU and followed by a mobile stroke team (MST-ICU) during an equal observation period of 27 months. Secondary objectives included comparing mortality and the proportion of patients with excellent outcomes (modified Rankin Score (mRS) 0-1). Equal cardiovascular monitoring was offered in patients admitted in both SI-SU and MST-ICU.458 patients were treated in the SI-SU and compared to the MST-ICU (n = 370) cohort. The proportion of death and dependency after 3 months was significantly improved for patients in the SI-SU compared to MST-ICU (p < 0.001; aOR = 0.45; 95% CI: 0.31-0.65). The shift analysis of the mRS distribution showed significant shift to the lower mRS in the SI-SU group, p < 0.001. The proportion of mortality in patients after 3 months also differed between the MST-ICU and the SI-SU (p < 0.05), but after adjusting for confounders this association was not significant (aOR = 0.59; 95% CI: 0.31-1.13). The proportion of patients with excellent outcome was higher in the SI-SU (59.4 vs. 44.9%, p < 0.001) but the relationship was no more significant after adjustment (aOR = 1.17; 95% CI: 0.87-1.5).Our study shows that moving from a stroke team in a monitored setting (ICU) to an organized stroke unit leads to a significant reduction in the 3 months unfavorable outcome in patients with an acute ischemic or hemorrhagic stroke. Cardiovascular monitoring is indispensable, but benefits of a semi-intensive Stroke Unit are driven by additional elements beyond intensive cardiovascular monitoring. This observation supports the ongoing development of Stroke Centers for efficient stroke care.

  View details for DOI 10.1159/000369919

  View details for PubMedID 25634579

• Aortic arch atheroma: a plaque of a different color or more of the same? Stroke; a journal of cerebral circulation George, P. M., Albers, G. W. 2014; 45 (5): 1239-1240

  View details for DOI 10.1161/STROKEAHA.114.004827

  View details for PubMedID 24699053

• Three-dimensional conductive constructs for nerve regeneration. Journal of biomedical materials research. Part A George, P. M., Saigal, R., Lawlor, M. W., Moore, M. J., LaVan, D. A., Marini, R. P., Selig, M., Makhni, M., Burdick, J. A., Langer, R., Kohane, D. S. 2009; 91 (2): 519-527

  Abstract

  The unique electrochemical properties of conductive polymers can be utilized to form stand-alone polymeric tubes and arrays of tubes that are suitable for guides to promote peripheral nerve regeneration. Noncomposite, polypyrrole (PPy) tubes ranging in inner diameter from 25 microm to 1.6 mm as well as multichannel tubes were fabricated by electrodeposition. While oxidation of the pyrrole monomer causes growth of the film, brief subsequent reduction allowed mechanical dissociation from the electrode mold, creating a stand-alone, conductive PPy tube. Conductive polymer nerve guides made in this manner were placed in transected rat sciatic nerves and shown to support nerve regeneration over an 8-week time period.

  View details for DOI 10.1002/jbm.a.32226

  View details for PubMedID 18985787

• Electrically controlled drug delivery from biotin-doped conductive polypyrrole ADVANCED MATERIALS George, P. M., LaVan, D. A., Burdick, J. A., Chen, C. Y., Liang, E., Langer, R. 2006; 18 (5): 577-+

  View details for DOI 10.1002/adma.200501242

  View details for Web of Science ID 000236379200007

• Electrically Controlled Drug Delivery from Biotin-Doped Conductive Polymer Advanced Materials George, P. M., LaVan, D., Burdick, J., Chen, C. Y., Liang, E., Langer, R. 2006; 18 (5)
• Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics BIOMATERIALS George, P. M., Lyckman, A. W., LaVan, D. A., Hegde, A., Leung, Y., Avasare, R., Testa, C., Alexander, P. M., Langer, R., Sur, M. 2005; 26 (17): 3511-3519

  Abstract

  Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

  View details for DOI 10.1016/j.biomaterials.2004.09.037

  View details for Web of Science ID 000226968200016

  View details for PubMedID 15621241

• Simple, three-dimensional microfabrication of electrodeposited structures ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LaVan, D. A., George, P. M., Langer, R. 2003; 42 (11): 1262-1265

  View details for Web of Science ID 000181872300008

  View details for PubMedID 12645058

• Fabrication of Screen-Printed Carbon Electrode Arrays for Sensing Neuronal Messengers BIOMEDICAL MICRODEVICES George, P. M., Muthuswamy, J., Currie, J., Thakor, N. V., Paranjape, M. 2001; 3 (4): 307-313

  View details for Web of Science ID 000209018800007