Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 21, Issue 11, Pages 1303-1309Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00004647-200111000-00006
Keywords
gene therapy; heat shock protein 72; ischemia; neuroprotection
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Funding
- NIGMS NIH HHS [GM49831] Funding Source: Medline
- NINDS NIH HHS [R01 NS40516, 5 PO1 NS37520 02] Funding Source: Medline
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The 72-kD inducible heat shock protein (HSP72) can attenuate cerebral ischemic injury when overexpressed before ischemia onset. Whether HSP72 overexpression is protective when applied after ischemia onset is not known, but would have important clinical implications. Fifty-seven rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral (HSV) vectors expressing hsp72 with lacZ as a reporter were delivered 0.5, 2, and 5 hours after ischemia onset into each striatum. Control animals received an identical vector containing only lacZ. Striatal neuron survival at 2 days was improved by 23% and 15% when HSP72 vectors were delayed 0.5 and 2 hours after ischemic onset, respectively (P < 0.05). However, when delayed by 5 hours, HSP72 overexpression was no longer protective. This is the first demonstration that HSP72 gene transfer even after ischemia onset is neuroprotective. Because expression from these HSV vectors begins 4 to 6 hours after injection, this suggests that the temporal therapeutic window for HSP72 is at least 6 hours after ischemia onset. Future strategies aimed at enhancing HSP72 expression after clinical stroke may be worth pursuing. The authors suggest that in the future HSP72 may be an effective treatment for stroke.
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