A5076413193- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Cardiac Arrest and Resuscitation
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Traumatic Brain Injury Research
- Neuroscience and Neuropharmacology Research
- Trauma and Emergency Care Studies
- Neurotransmitter Receptor Influence on Behavior
- Sepsis Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Neonatal and fetal brain pathology
- Receptor Mechanisms and Signaling
- Nerve injury and regeneration
- Anesthesia and Sedative Agents
- Cardiovascular Syncope and Autonomic Disorders
- Epilepsy research and treatment
- Intensive Care Unit Cognitive Disorders
- Amino Acid Enzymes and Metabolism
- Congenital Anomalies and Fetal Surgery
- Fetal and Pediatric Neurological Disorders
- Cerebrospinal fluid and hydrocephalus
- Pluripotent Stem Cells Research
- Pelvic and Acetabular Injuries
- Respiratory Support and Mechanisms
Cedars-Sinai Medical Center
2014-2021
Novartis (United States)
2021
Baxalta (United States)
2019
StemCells (United States)
2018
Columbia University
2016-2017
Banner - University Medical Center Tucson
2016
Regenerative Medicine Institute
2014-2015
University of California, Los Angeles
2014
St. Josef Krankenhaus
1982
Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by progressive loss of motor neurons leading to paralysis and death typically within 3–5 years onset. Recently, there has been remarkable progress in understanding inherited forms ALS which well defined mutations are known cause the disease. Rodent models superoxide dismutase-1 (SOD1) mutation overexpressed recapitulate hallmark signs patients. Early anatomical changes mouse fALS seen...
Abstract Early dysfunction of cortical motor neurons may underlie the initiation amyotrophic lateral sclerosis (ALS). As such, cortex represents a critical area ALS research and promising therapeutic target. In current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (GDNF) were transplanted into SOD1G93A rat cortex, where they migrated, matured astrocytes, released GDNF. This protected neurons, delayed disease pathology...
BACKGROUND β-Adrenergic receptor blockers (BBs) administered after trauma blunt the cascade of immune and inflammatory changes associated with injury. BBs are improved outcomes traumatic brain injury (TBI). Propranolol may be an ideal BB because its nonselective inhibition ability to cross blood-brain barrier. We determined if early administration propranolol TBI is lower mortality. METHODS All adults (age ≥ 18 years) moderate-to-severe (head Abbreviated Injury Scale [AIS] score, 3–5)...
Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate behavioral role of cotransmission, we targeted glutamate-recycling enzyme glutaminase (gene Gls1). In mice with dopamine transporter (Slc6a3)-driven conditional heterozygous (cHET) reduction Gls1 their neurons, neuron survival and transmission were unaffected, while cotransmission at phasic firing frequencies was reduced, enabling selective focus on cotransmission. The showed normal emotional motor...
Injecting proteins into the central nervous system that stimulate neuronal growth can lead to beneficial effects in animal models of disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has shown promise and Parkinson's disease, Huntington's disease amyotrophic lateral sclerosis (ALS). Here, systemic AAV9-GDNF was delivered via tail vein injections young rats determine whether this could be a safe functional strategy treat SOD1G93A rat model ALS and, therefore,...
Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to specific ligands. Here first time, we have implemented this address potential therapeutic value a glutamate-based schizophrenia involving inhibition glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous GLS1, gene encoding glutaminase, manifest resilience phenotype, key dimension which attenuated locomotor response...
Concussion injury is the most common form of traumatic brain (TBI). How recurrent concussions alter long-term outcomes poorly understood, especially as related to development neurodegenerative disease. We evaluated functional and pathological consequences repeated TBI over time in wild type (WT) rats well harboring human SOD1 mutation ("SOD1"), a model familial amyotrophic lateral sclerosis (ALS).A total 42 rats, 26 WT 16 SOD1, were examined study period 25 weeks (or endpoint). At postnatal...
The acute response of the rodent subventricular zone (SVZ) to traumatic brain injury (TBI) involves a physical expansion through increased cell proliferation. However, cellular underpinnings these changes are not well understood. Our analyses have revealed that there two distinct transit-amplifying populations respond in opposite ways injury. Mash1+ cells primary SVZ type is stimulated divide following TBI. In contrast, EGFR+ population, which has been considered be functionally equivalent...
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which upper and lower neurons degenerate, leading to muscle atrophy, paralysis, death within 3 5 years of onset. While small percentage ALS cases are genetically linked, the majority sporadic with unknown origin. Currently, etiological links associated onset without mechanistic understanding. Of all putative risk factors, however, head trauma has emerged as consistent candidate for initiating molecular cascades ALS. Here,...
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. symptoms include changes in mood, behavior, cognition, and motor function; however, CTE currently diagnosed only postmortem. Using rat model of recurrent brain injury (TBI), we demonstrate rodent deficits that predict the severity CTE-like pathology.Bilateral, closed-skull, mild TBI was administered once per week 35 wild-type rats; eight rats received two injuries (2×TBI), 27 five...
Traumatic brain injury (TBI) is a well-established risk factor for several neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, however, link between TBI amyotrophic lateral sclerosis (ALS) has not been clearly elucidated. Using the SOD1G93A rat model known to recapitulate human ALS condition, we found that exposure mild, repetitive lead rats experience earlier onset shortened survival relative their sham counterparts. Importantly, increased severity of early...
Summary The authors review 214 consecutive encephalograms from children mostly suffering epilepsy, oligophrenia, cerebral palsy, or various combinations of these symptoms. Sixty‐two patients had normal encephalograms, while almost all the others more less pronounced brain atrophy. Except in cases with one‐sided symptoms, no conspicuous correlation existed between nature symptoms electroencephalograms, and character atrophy, except that most epileptics pictures. Very often there was a...
Objective: Develop a gene replacement therapy for the treatment of Rett Syndrome. Background: syndrome is progressive neurodevelopmental disorder, affecting approximately 1 in 10,000 girls. patients experience loss achieved developmental milestones, including speech and motor function, beginning at 6–18 months age. Patients often survive 40–50 years but lifelong disability requiring intense supportive measures 24/7 care. caused by mutations X-linked methyl-CpG binding protein 2 (MeCP2) gene,...
To develop a first-in-human gene therapy for amyotrophic lateral sclerosis (ALS) using intrathecal AAV9-SOD1-shRNA administration.