Despite intensive experimental research activities devoted to neuronal injury following cerebral ischemia and trauma, our understanding of the mechanisms by which the neurons undergo necrosis and apoptosis is still rather poor. The objective of our CNS Injury and Edema Research Center is to employ both in vivo models of cerebral ischemia and trauma and in vitro cell culture systems to further elucidate cellular and molecular mechanisms of neuronal cell death. Our long-term goal is to develop pharmacological and therapeutic interventions to ameliorate the brain injuries. We will primarily focus on the role of oxidative stress, novel gene expression, and astrocytes on ischemic dismutase gene will be employed. Thus the research project of this proposal provides for interdisciplinary studies ranging from molecular biology, physiology, molecular genetics, biochemistry and morphology to investigate the basis of ischemic and traumatic brain injury. The program includes four interrelated projects: Oxidative stress and neuronal injury in cerebral ischemia; Role of stress protein and SOD expression on neuronal resistance to ischemia; Mechanism of subarachnoid hemorrhage-induced brain injury after head trauma; and Stress genes in cerebral ischemia. All projects are conceptually integrated with one another. Experimentally, they will rely heavily on the Scientific Core. Extensive utilization of transgenic and knockout mutant mice will provide a common vehicle for our interaction among the projects to study the mechanisms of neuronal injury following cerebral ischemia and trauma.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Neurological Disorders Program Project Review A Committee (NSPA)
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Jacobs, Tom P
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Kim, Jong Youl; Kim, Nuri; Yenari, Midori A et al. (2013) Hypothermia and pharmacological regimens that prevent overexpression and overactivity of the extracellular calcium-sensing receptor protect neurons against traumatic brain injury. J Neurotrauma 30:1170-6
Voloboueva, Ludmila A; Emery, John F; Sun, Xiaoyun et al. (2013) Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin. FEBS Lett 587:756-62
Tang, Xian Nan; Cairns, Belinda; Kim, Jong Youl et al. (2012) NADPH oxidase in stroke and cerebrovascular disease. Neurol Res 34:338-45
Cairns, Belinda; Kim, Jong Youl; Tang, Xian Nan et al. (2012) NOX inhibitors as a therapeutic strategy for stroke and neurodegenerative disease. Curr Drug Targets 13:199-206
Sakata, Hiroyuki; Niizuma, Kuniyasu; Wakai, Takuma et al. (2012) Neural stem cells genetically modified to overexpress cu/zn-superoxide dismutase enhance amelioration of ischemic stroke in mice. Stroke 43:2423-9
Voloboueva, Ludmila A; Giffard, Rona G (2011) Inflammation, mitochondria, and the inhibition of adult neurogenesis. J Neurosci Res 89:1989-96
Tang, Xian N; Zheng, Zhen; Giffard, Rona G et al. (2011) Significance of marrow-derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic stroke. Ann Neurol 70:606-15
Chen, Hai; Kim, Gab Seok; Okami, Nobuya et al. (2011) NADPH oxidase is involved in post-ischemic brain inflammation. Neurobiol Dis 42:341-8
Yoshioka, Hideyuki; Niizuma, Kuniyasu; Katsu, Masataka et al. (2011) NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia. J Cereb Blood Flow Metab 31:868-80
Xiong, Xiaoxing; Barreto, George E; Xu, Lijun et al. (2011) Increased brain injury and worsened neurological outcome in interleukin-4 knockout mice after transient focal cerebral ischemia. Stroke 42:2026-32

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