A5009140378- Pain Mechanisms and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Spinal Cord Injury Research
- Neurogenesis and neuroplasticity mechanisms
- Traumatic Brain Injury Research
- Cerebral Palsy and Movement Disorders
- Cardiac Arrest and Resuscitation
- Pain Management and Opioid Use
- Pediatric Pain Management Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Nerve Injury and Rehabilitation
- Ion channel regulation and function
- Retinopathy of Prematurity Studies
- Neuropeptides and Animal Physiology
- Stroke Rehabilitation and Recovery
- Anesthesia and Pain Management
- Spinal Dysraphism and Malformations
- Nerve injury and regeneration
- Transcranial Magnetic Stimulation Studies
- Neuroscience and Neuropharmacology Research
- Glioma Diagnosis and Treatment
- Cervical and Thoracic Myelopathy
- Pluripotent Stem Cells Research
- Clusterin in disease pathology
Stanford Medicine
2024
Stanford University
2013-2023
VA Palo Alto Health Care System
2016-2023
San Francisco VA Medical Center
2011-2022
University of California, San Francisco
2008-2022
Neurological Surgery
2008-2014
University of Cambridge
2007-2008
Multiple Sclerosis Society
2006-2008
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects damage oligodendrocytes and failure remyelination. A common feature demyelinated lesions is presence oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, mechanistic basis for inhibition repair incompletely understood. To identify novel regulators OLP differentiation, potentially dysregulated during repair, we performed genome-wide screen...
In multiple sclerosis, demyelination of the CNS axons is associated with axonal injury and degeneration, which now accepted as major cause neurological disability in disease. Although kinetics extent damage have been described detail, mechanisms by it occurs are yet unclear; one suggestion failure remyelination. The goal this study was to test hypothesis that prompt remyelination contributes degeneration following demyelination. Remyelination inhibited exposing brain 40 Gy X-irradiation...
Abstract Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets enhance for precision medicine. Here we describe the application of topological analysis (TDA) data-driven preclinical traumatic brain injury (TBI) and spinal cord (SCI) mined Visualized Syndromic Information Outcomes Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization inter-related histopathological, functional health...
Spinal cord injury (SCI) and other neurological disorders involve complex biological functional changes. Well-characterized preclinical models provide a powerful tool for understanding mechanisms of disease; however managing information produced by experimental represents significant challenge translating findings across research projects presents substantial hurdle translation novel therapies to humans. In the present work we demonstrate 'syndromic' information-processing approach...
purpose. Glaucoma is a common neurodegenerative disease for which current therapies are often insufficient; thus, new neuroprotective strategies an important goal. Stem cells attracting increasing attention as mediators of neuroprotection, conferred via the trophic support injured neurons. The purpose our investigation was to determine whether oligodendrocyte precursor (OPCs), type neural stem cell, can protect retinal ganglion (RGCs) from glaucomatous damage in vivo. methods. Intraocular...
Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because large, heterogeneous data sets involved. In this sense, translational neurological represents a "big data" problem. an effort expedite knowledge standards patient care for SCI, we describe development novel database known as Visualized...
A major advancement in the field of analgesic pharmacology has been development G-protein-biased opioid agonists that display less respiratory depression than conventional drugs. It is uncertain, however, whether these new drugs cause tolerance, hyperalgesia, and other maladaptations when administered repeatedly.The archetypical µ-opioid receptor agonist morphine and, separately, oliceridine were to mice. These used models acute analgesia, opioid-induced reward, physical dependence. In...
Human embryonic stem cells (hESCs) are a potential source of defined tissue for cell-based therapies in regenerative neurology. In order this to be realized, there is need the evaluation behaviour human cell-derived neural (hES-NSCs) both normal and injured CNS. Using two experimental models, we examined response clinically compatible hES-NSCs physiological pathological signals. We demonstrate that phenotypic multipotent population influenced by these cues vitro vivo. display temporal...
The IBB scale is a recently developed forelimb for the assessment of fine control and digits after cervical spinal cord injury (SCI; Irvine et al., 2010). present paper describes inter-rater reliability face, concurrent construct validity this following SCI. It demonstrates that reliable valid sensitive to severity SCI recovery over time. In addition, correlates with other outcome measures highly predictive biological tissue pathology. Multivariate analysis using principal component (PCA)...
Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences damage this level (Pearse et al., 2005, Gensel 2006, Anderson 2009), as majority human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss forelimb function due white matter affecting both descending motor and ascending sensory systems, gray containing segmental circuitry for processing input output forelimb. Additionally, a key priority...
The primate corticospinal tract (CST), the major descending pathway mediating voluntary hand movements, comprises nine or more functional subdivisions. role of subcomponents other than that from primary motor cortex, however, is not well understood. We have previously shown following a cervical dorsal rhizotomy (Darian-Smith et al., 2013), CST projections originating somatosensory (S1) and (M1) cortex responded quite differently to injury. Terminal S1 (areas 3b/1/2) shrank <60%...
The adult bone marrow contains a population of multipotent mesenchymal stromal cells (MSCs), defined by plastic adherence, expression cell surface markers, and differentiation into lineages. There has been much interest in the possible therapeutic use MSCs treatment demyelinating diseases central nervous system. One possibility is that these may be able to remyelinate when directly injected demyelinated spinal cord. Here we examine effects direct transplantation green fluorescent protein...
Abstract High rates of acute and chronic pain are associated with traumatic brain injury (TBI), but mechanisms responsible for the association remain elusive. Recent data suggest dysregulated descending modulation circuitry could be involved. Based on these other observations, we hypothesized that serotonin (5-HT)-dependent activation spinal CXC Motif Chemokine Receptor 2 (CXCR2) may support TBI-related nociceptive sensitization in a mouse model mild TBI (mTBI). We observed systemic 5-HT...
Abstract This study was designed to investigate whether the residual, dysfunctional oligodendrocyte progenitor cells (OPCs) observed following X‐irradiation of mouse spinal cord [D. M. Chari et al . (2003 ) Exp. Neurol. , 198, 145–153], presence which prevented endogenous repopulation these areas from normal tissue, reflects a general response OPCs in central nervous system (CNS) X‐irradiation. The brains adult mice were exposed 40 Gy and effect on assessed up 4 weeks post‐irradiation using...
Abstract Clinical spinal cord injury (SCI) is accompanied by comorbid peripheral in 47% of patients. Human and animal modeling data have shown that painful injuries undermine long-term recovery locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity dorsal horn sensory systems AMPA receptor (AMPAR) phosphorylation trafficking to synapses. Here we test whether ventral motor neurons rats demonstrate similar experience-dependent below a...
Chronic pain is a common consequence of traumatic brain injury (TBI) that can increase the suffering patient and pose significant challenge to rehabilitative efforts. Unfortunately, mechanisms linking TBI are poorly understood, specific treatments for TBI-related still lacking. Our laboratory has shown causes sensitization in areas distant site primary injury, changes spinal gene expression may underlie this sensitization. The aim study was examine roles modulatory pathways descending from...
Abstract Editor’s Perspective What We Already Know about This Topic Article Tells Us That Is New Background Emerging evidence suggests that opioid use immediately after surgery and trauma may worsen outcomes. In these studies, the authors aimed to determine whether morphine administered for a clinically relevant time period (7 days) in tibia fracture orthopedic model had adverse effects on postoperative recovery. Methods Mice were given twice daily 7 days unilateral tibial intramedullary pin...