NDLI: Neuroprotective potential of a viral vector system induced by a neurological insult.

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Neuroprotective potential of a viral vector system induced by a neurological insult.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sapolsky, R. M. Ozawa, C. R. Ho, J. J. Ho, D. Y. Tsai, D. J.
Description	Author Affiliation: Ozawa CR ( Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.);
Abstract	Gene transfer into neurons via viral vectors for protection against acute necrotic insults has generated considerable interest. Most studies have used constitutive vector systems, limiting the ability to control transgene expression in a dose-dependent, time-dependent, or reversible manner. We have constructed defective herpes simplex virus vectors designed to be induced by necrotic neurological insults themselves. Such vectors contain a synthetic glucocorticoid-responsive promoter, taking advantage of the almost uniquely high levels of glucocorticoids-adrenal stress steroids-secreted in response to such insults. We observed dose-responsive and steroid-specific induction by endogenous and synthetic glucocorticoids in hippocampal cultures. Induction was likely to be rapid enough to allow transgenic manipulation of relatively early steps in the cascade of necrotic neuron death. The protective potential of such a vector was tested by inclusion of a neuroprotective transgene (the Glut-1 glucose transporter). Induction of this vector by glucocorticoids decreased glutamatergic excitotoxicity in culture. Finally, both exogenous glucocorticoids and excitotoxic seizures induced reporter gene expression driven from a glucocorticoid-responsive herpes simplex virus vector in the hippocampus in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Defective Viruses Genetics Genetic Vectors Neuroprotective Agents Administration & Dosage Simplexvirus Animals Cells, Cultured Glucocorticoids Pharmacology Hippocampus Cytology Drug Effects Kainic Acid Rats, Sprague-Dawley Seizures Chemically Induced Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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