Adeno-associated virus-mediated delivery of BCL-w gene improves outcome after transient focal cerebral ischemia.
A recombinant adeno-associated virus (rAAV) vector was used to overexpress the anti-apoptotic Bcl-2-family protein, BCL-w, in rat brain. Three weeks after injecting the vector into cerebral cortex and striatum on one side, temporary focal ischemia was induced by occlusion of the ipsilateral middle cerebral artery for 90 min, followed by reperfusion for 24 h. BCL-w expression was increased in cerebral cortex and striatum--and in neurons, astroglia and endothelial cells--in the brains of rats that received the rAAV-BCL-w vector, compared to rats given phosphate-buffered saline or a control vector containing the gene for green fluorescent protein. Recipients of the rAAV-BCL-w vector also showed a 30% reduction in infarct size and a 33-40% improvement in neurological function, compared to the control groups. These results provide evidence for a role of BCL-w in regulating histological and functional outcome after focal cerebral ischemia.
Sun
Y
Y
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Jin
K
K
Clark
K R
KR
Peel
A
A
Mao
X O
XO
Chang
Q
Q
Simon
R P
RP
Greenberg
D A
DA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods
C491072:Bcl2l2 protein, rat; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2