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 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 hsp72 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.
Yenari
M A
MA
Department of Neurosurgery, Stanford Stroke Center, Stanford University Medical Center, CA 94304, USA.
Fink
S L
SL
Sun
G H
GH
Chang
L K
LK
Patel
M K
MK
Kunis
D M
DM
Onley
D
D
Ho
D Y
DY
Sapolsky
R M
RM
Steinberg
G K
GK
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control; D002470:Cell Survival / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000628:therapy*; D004827:Epilepsy / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018139:Simplexvirus / Q000235:genetics; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D001616:beta-Galactosidase; D007608:Kainic Acid