Molecular mechanisms of ischemic brain damage. Therapy for cerebral ischemia. Role of stress proteins in the cellular defense against ischemia. Development of RNA therapy to overexpress specific proteins in the brain.
Cerebral Ischemia, Neuronal Death, Stress Proteins, Cortical Spreading Depression, RNA therapy.
Rodent models of cerebral ischemia and spreading depression; histology; immunohistochemistry; quantitative microassay; molecular biology (in situ hybridization; Northern blot, Western blot, RT-PCR, gene transfer); laser-Doppler flowmetry, histopathology.
The brain is extremely vulnerable to ischemia. Loss of blood flow for only a few minutes triggers pathologic cascades that culminate in the death of the most vulnerable neurons. However, recent studies have demonstrated that this vulnerability can be dramatically reduced by preconditioning the brain with brief ischemia or cortical spreading depression. These results indicate that there are intrinsic mechanisms that protect neurons against ischemia. The objective of the lab is to identify those mechanisms and to explore therapeutic modalities based on them. In addition, the lab is developing RNA vectors to overexpress selected proteins in the brain.
Muramatsu H, Welsh FA, Karikó K: Cerebral preconditioning using cortical application of hypertonic salt solutions: upregulation of mRNAs encoding inhibitors of inflammation. Brain Res 1097(1): 31-38, Jun 2006.
Otori T, Friedland JC, Simon G, Mcintosh TK, Raghupathi R, Welsh FA.: Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat brain. J Neurotrauma 21(6): 707-718, Jun 2004.
Muramatsu H, Karikó K, Welsh FA: Induction of tolerance to focal ischemia in rat brain: Dissociation between cortical lesioning and spreading depression. J Cereb Blood Flow Metab 24(10): 1167-1171, Oct 2004.
Lifshitz J, Friberg H, Neumar RW, Raghupathi R, Welsh FA, Janmey P, Saatman KE, Wieloch T, Grady MS, McIntosh TK: Structural and functional damage sustained by mitochondria after traumatic brain injury in the rat: Evidence for differentially sensitive populations in the cortex and hippocampus. J Cereb Blood Flow Metab 23(2): 219-231, Feb 2003.
Otori T, Greenberg JH, Welsh FA: Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to permanent focal ischemia in rat brain. J Cereb Blood Flow Metab 23(1): 43-50, Jan 2003.
Mitchell K, Karikó K, Harris VA, Rangel Y, Keller JM, Welsh FA: Preconditioning with cortical spreading depression does not upregulate Cu/Zn-SOD or Mn-SOD in the cerebral cortex of rats. Mol Brain Res 96(1-2): 50-58, Nov 2001.
Neumar RW, Meng FH, Mills AM, Xu YA, Zhang C, Welsh FA, Siman R: Calpain activity in the rat brain after transient forebrain ischemia. Exp Neurol 170(1): 27-35, Jul 2001.
Rangel YM, Karikó K, Harris VA, Duvall ME, Welsh FA: Dose-dependent induction of mRNAs encoding brain-derived neurotrophic factor and heat-shock protein-72 after cortical spreading depression in the rat. Mol Brain Res 88(1-2): 103-112, Mar 2001.
Karikó K, Keller JM, Harris VA, Langer DJ, Welsh FA: In vivo protein expression from mRNA delivered into adult rat brain. J Neurosci Meth 105(1): 77-86, Jan 2001.
O'Dell DM, Muir JK, Zhang C, Bareyre FM, Saatman KE, Raghupathi R, Welsh F, McIntosh TK: Lubeluzole treatment does not attenuate neurobehavioral dysfunction or CA3 hippocampal neuronal loss following traumatic brain injury in rats. Restor Neurol Neurosci 16(2): 127-134, 2000.
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Last updated: 09/19/2012
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