Journal
ANESTHESIA AND ANALGESIA
Volume 97, Issue 2, Pages 564-571Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1213/01.ANE.0000068880.82739.7B
Keywords
-
Categories
Funding
- NIGMS NIH HHS [R01GM067139-01, R01GM52212-07] Funding Source: Medline
Ask authors/readers for more resources
The mechanisms by which anesthetics such as isoflurane reduce cell death in rodent models of cerebral ischemia remain incompletely defined. Reduction in glutamate excitotoxicity explains some but not all of isoflurane's neuroprotection. Because isoflurane potentiates gamma-aminobutyric acid (GABA) receptor-mediated ion fluxes and GABA, receptor agonists have neuroprotective effects, we hypothesized that GABA(A) receptors contribute to isoflurane neuroprotection. As a model of cerebral ischemia and recovery, we used rat hippocampal slice cultures. Survival of CA1, CA3, and dentate neurons was examined 2 and 3 days after 1-h combined oxygen-glucose deprivation (OGD) at 37degreesC. To define the role of GABAA receptors in mediating protection, the effect of 1% isoflurane on cell survival was examined in the presence of the GABA(A), antagonist bicuculline during OGD. Cell death was measured with propidium iodide fluorescence. Isoflurane and the selective GABA, agonist muscimol (25 muM) reduced cell death after OGD to values similar to slices not exposed to OGD, with the exception that muscimol did not reduce cell death in CA3 neurons 2 days after OGD. The GABA, antagonist bicuculline reduced the neuroprotective effects of isoflurane on hippocampal neurons 2 and 3 days after OGD. We conclude that GABA(A) receptors contribute to neuroprotection against OGD produced by isoflurane in the hippocampal slice model. Based on this and other studies, it is likely that neuroprotection produced by isoflurane is multifactorial and includes actions at both GABA, and glutamate receptors and possibly other mechanisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available