Neurology Commons^™

Endovascular Stroke Therapy Results Improve Over Time: The ‘Learning Curve’ At A New Comprehensive Stoke Center, Ethan A. Benardete, Anil K. Nair

Department of Neurosurgery Faculty Papers

Background: The requirements for a comprehensive stroke center (CSC) include the capability to perform endovascular stroke therapy (EST). EST is a complex process requiring early identification of appropriate patients and effective delivery of intervention. In order to provide prompt intervention for stroke, CSCs have been established away from large academic centers in community-based hospitals. We hypothesized that quantifiable improvements would occur during the first 2 years of a community-based CSC as the processes and personnel evolved. We report the results over time of EST at a new community-based CSC. Methods: We have retrospectively analyzed demographic data and outcome metrics of …

Neurosurgery Concepts: Key Perspectives On Dendritic Cell Vaccines, Metastatic Tumor Treatment, And Radiosurgery, Gordon Li, Jonathan H. Sherman, Jin Mo Cho, Michael Lim, Alexander A. Khalessi, Chaim B. Colen, Chae Yong Kim, Viincent Yat Wang, Gabriel Zada, Zachary A. Smith, Isaac Yang

Neurological Surgery Faculty Publications

Background: This is a laboratory study to investigate the effect of adding brain-derived-neurotrophic factor (BDNF) in a poly (N-isopropylacrylamide-g-poly (ethylene glycol) scaffold and its effect on spinal cord injury in a rat model.

Methods: This is a laboratory investigation of a spinal cord injury in a rat model. A dorsolateral funiculotomy was used to disrupt the dorsolateral funiculus and rubrospinal tract. Animals were then injected with either the scaffold polymer or scaffold polymer with BDNF. Postoperatively, motor functions were assessed with single pellet reach to grasp task, stair case reaching task and cylinder task. Histological study …

Principles Of Using Cold Atmospheric Plasma Stimulated Media For Cancer Treatment, Dayun Yan, Annie Talbot, Niki Nourmohammadi, Xiaoqian Cheng, Jerome Canady, Jonathan H. Sherman, Michael Keidar

Neurological Surgery Faculty Publications

To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation, Marta S. Vismer, Patrick A. Forcelli, Mark D. Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of the limbic and cortical regions of the mammalian brain provide the substrate for the hypersynchrony and hyperexcitability associated with epilepsy and seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition …

Proteomic Profiling Of High Risk Medulloblastoma Reveals Functional Biology, Jerome A. Staal, Ling San Lau, Huizhen Zhang, Wendy J. Ingram, Andrew R. Hallahan, Roger J. Packer, Brian R. Rood, Kristy J. Brown, +6 Additional Authors

Neurology Faculty Publications

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in …

The Piriform, Perirhinal, And Entorhinal Cortex In Seizure Generation., Marta S Vismer, Patrick A Forcelli, Mark D Skopin, Karen Gale, Mohamad Z. Koubeissi

Neurology Faculty Publications

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are …

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …

Implications Of Epigenetic Variability Within A Cell Population For "Cell Type" Classification, I. Tabansky, J. N.H. Stern, D. W. Pfaff

Journal Articles

Here, we propose a new approach to defining nerve "cell types" in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A "cell type" could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be …

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial With Recombinant Anti-Il-20 Monoclonal Antibody In Patients With Psoriasis, A. B. Gottlieb, J. G. Krueger, M. Sandberg Lundblad, M. Gothberg, B. E. Skolnick

Journal Articles

BACKGROUND: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20. METHODS: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area >/=15% and physician global assessment score >/=3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 …

Reduced Functional Connectivity Of Default Mode And Set-Maintenance Networks In Ornithine Transcarbamylase Deficiency., Ileana Pacheco-Colón, Stuart D. Washington, Courtney Sprouse, Guy Helman, Andrea L. Gropman, John W. Vanmeter

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks-default mode and set-maintenance-between OTCD patients and healthy controls.

METHODS: Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.

RESULTS: Group comparisons revealed …

Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey

Journal Articles

Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …

Hmgb1 Mediates Anemia Of Inflammation In Murine Sepsis Survivors, S. I. Valdes-Ferrer, J. Papoin, M. E. Dancho, L. P. S. Olofsson, J. Li, J. M. Lipton, P. Avancena, H. Yang, Y. R. Zou, S. S. Chavan, B. T. Volpe, S. Rivella, B. Diamond, B. M. Steinberg, L. Blanc, K. J. Tracey, +2 Additional Authors

Journal Articles

Patients surviving sepsis develop anemia but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial Gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating TNF and IL-6 are elevated for five days after the onset of sepsis, and serum HMGB1 levels are increased from day seven until at least day 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after …

Stress Induces The Danger-Associated Molecular Pattern Hmgb-1 In The Hippocampus Of Male Sprague Dawley Rats: A Priming Stimulus Of Microglia And The Nlrp3 Inflammasome, M. D. Weber, M. G. Frank, K. J. Tracey, L. R. Watkins, S. F. Maier

Journal Articles

Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the …

Combining Task-Evoked And Spontaneous Activity To Improve Pre-Operative Brain Mapping With Fmri, M. D. Fox, T. Qian, J. R. Madsen, D. Wang, M. Ge, H. C. Zuo, D. M. Groppe, A. D. Mehta, B. Hong, H. Liu, +1 Additional Author

Journal Articles

Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional …

Galantamine Attenuates Type 1 Diabetes And Inhibits Anti-Insulin Antibodies In Non-Obese Diabetic Mice, W. M. Hanes, P. S. Olofsson, K. Kwan, L. K. Hudson, S. S. Chavan, V. A. Pavlov, K. J. Tracey

Journal Articles

Type 1 diabetes in mice is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Disease pathogenesis involves invasion of pancreatic islets by immune cells, including macrophages and T cells, and production of antibodies to self-antigens, including insulin. Activation of the inflammatory reflex, the neural circuit that inhibits inflammation, culminates on cholinergic receptor signals on immune cells to attenuate cytokine release and inhibit B cell antibody production. Here, we show that galantamine, a centrally acting acetylcholinesterase inhibitor and an activator of the inflammatory reflex, attenuates murine experimental type 1 diabetes. Administration of galantamine to animals immunized with keyhole limpet hemocyanin …

Damp Signaling Is A Key Pathway Inducing Immune Modulation After Brain Injury, A. Liesz, A. Dalpke, E. Mracsko, D. J. Antoine, S. Roth, W. Zhou, H. Yang, P. P. Nawroth, K. J. Tracey, R. Veltkamp, +4 Additional Authors

Journal Articles

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, …

Regulation Of Post-Translational Modifications Of Hmgb1 During Immune Responses, B. Lu, Y. Tang, X. Zhao, D. Antoine, X. Xiao, H. Wang, U. Andersson, T. Billiar, K. J. Tracey

Journal Articles

SIGNIFICANCE: High mobility group protein 1 (HMGB1) is an evolutionarily conserved and multi-functional protein. The biological function of HMGB1 depends on its cellular locations, binding partners, and redox states. Extracellular HMGB1 is a mediator of inflammation during infection or tissue injury. Immune cells actively release HMGB1 in response to infection, which in turn orchestrates both innate and adaptive immune responses. RECENT ADVANCES: Hyperacetylation of HMGB1 within its nuclear localization sequences mobilizes HMGB1 from the nucleus to the cytoplasm and subsequently promotes HMGB1 release. The redox states of the cysteines in position 23, 45 and 106 determine the biological activity of …

A Unifying Principle Underlying The Extracellular Field Potential Spectral Responses In The Human Cortex, E. Podvalny, N. Noy, M. Harel, S. Bickel, G. Chechik, C. E. Schroeder, A. D. Mehta, M. Tsodyks, R. Malach

Journal Articles

Electrophysiological mass potentials show complex spectral changes upon neuronal activation. However, it is unknown to what extent these complex band-limited changes are interrelated or, alternatively, reflect separate neuronal processes. To address this question, intracranial electrocorticograms (ECoG) responses were recorded in patients engaged in visuomotor tasks. We found that in the 10- to 100-Hz frequency range there was a significant reduction in the exponent chi of the 1/f(chi) component of the spectrum associated with neuronal activation. In a minority of electrodes showing particularly high activations the exponent reduction was associated with specific band-limited power modulations: emergence of a high gamma (80-100 …

Clinical Reasoning: Worsening Neurologic Symptoms In A Brain Tumor Patient, G. Faivre, E. Pentsova, A. Demopoulos, S. Taillibert, M. Rosenblum, A. Omuro

Journal Articles

No abstract provided.