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Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy
Author(s) -
Yenari Midori A.,
Fink Sheri L.,
Sun Guo Hua,
Chang Louis K.,
Patel Maitrya K.,
Kunis David M.,
Onley David,
Ho Dora Y.,
Sapolsky Robert M.,
Steinbrg Gary K.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440403
Subject(s) - neuroprotection , dentate gyrus , kainic acid , neuroscience , medicine , epilepsy , ischemia , neuron , hippocampal formation , stroke (engine) , heat shock protein , pharmacology , biology , gene , biochemistry , glutamate receptor , receptor , mechanical engineering , engineering
Brain areas damaged by stroke and seizures express high levels of the 27‐kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp 72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin‐induced seizures.