(Stroke. 1995;26:1670-1675.)
© 1995 American Heart Association, Inc.
Articles |
Expression of bcl-2 From a Defective Herpes Simplex Virus–1 Vector Limits Neuronal Death in Focal Cerebral Ischemia
From the Department of Neurosurgery, University of Cincinnati (Ohio) College of Medicine, Marion Merrell Dow Research Institute (M.D.L.), and the Departments of Medicine and Neuroscience (P.Z., M.D.G., H.J.F.) and Neurosurgery (P.Z.), Albert Einstein College of Medicine, Bronx, NY.
Correspondence to Howard J. Federoff, MD, PhD, Department of Neurology, Box 673, University of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642.
Background and Purpose A process resembling programmed cell death appears to contribute to postischemic neuronal loss in several models of stroke. Because the expression of the bcl-2 gene has been shown to rescue neurons from programmed cell death due to other causes, we determined whether it would be similarly neuroprotective in stroke.
Methods Replication defective herpes viral vectors that transduce bcl-2 (HSVbcl2) or Escherichia coli lacZ (HSVlac) were injected into two sites in the rat cerebral cortex 24 hours before induction of neocortical focal ischemia by tandem permanent occlusion of the right middle cerebral artery and ipsilateral common carotid artery. Local ischemic damage was determined 24 hours after occlusion by staining with 2% 2,3,5-triphenyltetrazolium chloride.
Results Expression of bcl-2 in cerebral cortex was confirmed by immunohistochemistry in animals injected with the HSVbcl2 expression vector. Viable tissue was significantly increased at the injection sites in HSVbcl2- but not HSVlac-injected animals. The protection observed in the HSVbcl2 animals was localized to the injection sites.
Conclusions These data indicate that bcl-2 expression protects neurons in vivo from ischemic injury and suggest the feasibility of gene therapy for stroke and perhaps other neurological diseases in which programmed cell death is involved.
Key Words: apoptosis • cerebral ischemia • genetics • herpes simplex • neuronal death
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