GENE-THERAPY WITH HSP72 IS NEUROPROTECTIVE IN RAT MODELS OF STROKE AND EPILEPSY

Brain areas damaged by stroke and seizures express high levels of the 72-kd heat shock protein (HSP72). Whether HSP72 represents merely a ma rker of stress or plays a role in improving neuron survival in these c ases has been debated. Some induced tolerance experiments have provide d correlative evidence for a neuroprotective effect, and others have d ocumented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vector s overexpressing hsp72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpressio n improved striatal neuron survival from 62.3 to 95.4% in rats subject ed to 1 hour of middle cerebral artery occlusion, and improved surviva l of hippocampal dentate gyrus neurons after systemic kainic acid admi nistration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cere bral ischemia and excitotoxin-induced seizures.