PMID- 7544927
OWN - NLM
STAT- MEDLINE
DCOM- 19951004
LR  - 20190727
IS  - 0039-2499 (Print)
IS  - 0039-2499 (Linking)
VI  - 26
IP  - 9
DP  - 1995 Sep
TI  - Expression of bcl-2 from a defective herpes simplex virus-1 vector limits 
      neuronal death in focal cerebral ischemia.
PG  - 1670-4; discussion 1675
AB  - 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 of 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.
FAU - Linnik, M D
AU  - Linnik MD
AD  - Department of Neurosurgery, University of Cincinnati College of Medicine, Marion 
      Merrell Dow Research Institute, Ohio, USA.
FAU - Zahos, P
AU  - Zahos P
FAU - Geschwind, M D
AU  - Geschwind MD
FAU - Federoff, H J
AU  - Federoff HJ
LA  - eng
GR  - GM7288-16/GM/NIGMS NIH HHS/United States
GR  - HD27116/HD/NICHD NIH HHS/United States
GR  - HD31300/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tetrazolium Salts)
RN  - 7OL20RET2I (triphenyltetrazolium)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
GS  - bcl-2
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Cerebral Cortex/metabolism/virology
MH  - Escherichia coli
MH  - GTP-Binding Proteins/genetics/metabolism
MH  - *Gene Expression Regulation, Viral
MH  - *Genetic Vectors
MH  - Herpesvirus 1, Human/*genetics
MH  - Ischemic Attack, Transient/genetics/*pathology/virology
MH  - Neurons/*pathology
MH  - Neuroprotective Agents
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Proto-Oncogenes/*genetics
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Staining and Labeling
MH  - Tetrazolium Salts
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 10.1161/01.str.26.9.1670 [doi]
PST - ppublish
SO  - Stroke. 1995 Sep;26(9):1670-4; discussion 1675. doi: 10.1161/01.str.26.9.1670.