Overexpression of HSP72 after induction of experimental stroke protects neurons from ischemic damage

The 72-kD inducible heat shock protein (HSP72) can attenuate cerebral ische mic injury when overexpressed before ischemia onset. Whether HSP72 overexpr ession is protective when applied after ischemia onset is not known, but wo uld 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, an d 5 hours after ischemia onset into each striatum. Control animals received an identical vector containing only lacZ. Striatal neuron survival at 2 da ys was improved by 23% and 15% when HSP72 vectors were delayed 0.5 and 2 ho urs 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 neuropr otective. Because expression from these HSV vectors begins 4 to 6 hours aft er injection, this suggests that the temporal therapeutic window for HSP72 is at least 6 hours after ischemia onset. Future strategies aimed at enhanc ing HSP72 expression after clinical stroke may be worth pursuing. The autho rs suggest that in the future HSP72 may be an effective treatment for strok e.