DOI: 10.1161/01.str.26.9.1670. Expression of bcl-2 From a Defective Herpes Simplex Virus–1 Vector Limits Neuronal Death in Focal Cerebral Ischemia

Expression of bcl-2 From a Defective Herpes Simplex Virus–1 Vector Limits Neuronal Death in Focal Cerebral Ischemia

10.1161/01.str.26.9.1670

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

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.

Bibliography

Linnik, M. D., Zahos, P., Geschwind, M. D., & Federoff, H. J. (1995). Expression of bcl-2 From a Defective Herpes Simplex Virusâ1 Vector Limits Neuronal Death in Focal Cerebral Ischemia. Stroke, 26(9), 1670â1675.

Authors 4

Matthew D. Linnik (first)
Peter Zahos (additional)
Michael D. Geschwind (additional)
Howard J. Federoff (additional)

References 50 Referenced 234

10.1146/annurev.ne.13.030190.001131
10.1016/0891-5849(89)90057-9
10.1016/0006-8993(90)90144-Z
10.1161/str.24.12.8248983
10.1161/str.25.4.8160232
10.1111/j.1471-4159.1993.tb09843.x
10.1016/0304-3940(93)90864-H
10.1097/00001756-199401120-00031
10.1038/jcbfm.1994.119
10.1146/annurev.cb.07.110191.003311
10.1146/annurev.ne.14.030191.002321
10.1146/annurev.ne.16.030193.000335
10.1126/science.8235659
10.1016/0169-328X(93)90139-G
10.1006/bbrc.1993.2571
10.1016/0092-8674(93)90230-N
10.1016/0896-6273(94)90266-6
10.1016/0896-6273(90)90171-B
10.1073/pnas.89.5.1636
10.1089/hum.1992.3.5-487
10.1016/0014-4886(92)90196-W
10.1089/hum.1992.3.1-11
Breakefield X Huang Q Andersen J Kramer M Bebrin W Davar G Vos B Garber D Difiglia M Coen D. Gene transfer into the nervous system using recombinant herpes virus vectors. In: Gage F Christen Y eds. Gene Transfer and Therapy in the Nervous System. Heidelberg FRG: Springer-Verlag; 1992:45-48. (10.1007/978-3-642-84842-1_10)
10.1128/MCB.8.1.457
10.1016/1044-7431(91)90062-S
10.1073/pnas.90.8.3655
10.1126/science.266.5189.1399
10.1126/science.2843986
10.1016/0169-328X(94)90146-5
10.1006/dbio.1994.1131
10.1523/JNEUROSCI.13-03-00941.1993
10.1073/pnas.90.13.6165
Geschwind M Lu B Federoff H. Viral transfection of intrinsic cells within the brain: expression of neurotrophic genes from HSV-1 vectors: modifying neuronal phenotype. In: Conn PM ed. Providing Pharmacological Access to the Brain. Orlando Fl: Academic Press Inc; 1994:462-482. (10.1016/B978-0-12-185291-7.50033-3)
Federoff H. Growth of replication defective herpes virus amplicon vectors and their use for gene transfer. In: Spector D Goldman R Lienwand L eds. Cell Biology: A Laboratory Manual. Cold Spring Harbor NY: Cold Spring Harbor Press; 1995.
Johnson P, Miyanohara A, Levine F, Cahill T, Friedman T. Cytotoxicity of replication-defective mutant of herpes simplex virus type 1. J Virol. 1992;66:2952-2965. (10.1128/jvi.66.5.2952-2965.1992) / J Virol (1992)
10.1099/0022-1317-71-8-1775
Paxinos GT Watson C. The Rat Brain in Stereotaxic Coordinates. 2nd ed. New York NY: Academic Press; 1986.
10.1111/j.1365-2990.1988.tb00889.x
10.1038/jcbfm.1988.88
10.1161/01.STR.17.4.738
Casals-Hatem D, Louie D, Tanaka S, Reed J. Molecular cloning and DNA sequence analysis of cDNA encoding chicken homolog of the bcl-2 oncoprotein. Biochem Biophys Acta. 1992;1132:109-113. / Biochem Biophys Acta (1992)
10.1128/MCB.9.2.701
10.1038/348334a0
10.1073/pnas.89.16.7295
10.1038/361365a0
10.1016/S0021-9258(18)82073-7
10.1016/0092-8674(93)80066-N
10.1073/pnas.90.10.4533
10.1038/371336a0
10.1016/0304-3940(95)11310-S

Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 6:02 p.m.)
Indexed	3 months ago (May 27, 2025, 2:03 a.m.)
Issued	29 years, 11 months ago (Sept. 1, 1995)
Published	29 years, 11 months ago (Sept. 1, 1995)
Published Print	29 years, 11 months ago (Sept. 1, 1995)

Funders 0

None

BibTeX

@article{Linnik_1995, title={Expression of bcl-2 From a Defective Herpes Simplex Virus–1 Vector Limits Neuronal Death in Focal Cerebral Ischemia}, volume={26}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.26.9.1670}, DOI={10.1161/01.str.26.9.1670}, number={9}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Linnik, Matthew D. and Zahos, Peter and Geschwind, Michael D. and Federoff, Howard J.}, year={1995}, month=sep, pages={1670–1675} }

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