Isoflurane and pentobarbital reduce AMPA toxicity in vivo in the rat cerebral cortex.
BACKGROUND
Isoflurane and pentobarbital can reduce alpha-amino-d-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated toxicity in vitro. However, their effect on AMPA toxicity in vivo is not known. The present study was undertaken to evaluate the effects of isoflurane and pentobarbital on the in vivo neurotoxicity produced by AMPA.


METHODS
Wistar-Kyoto rats were allocated to one of seven groups (n = 8 per group): isoflurane 1 minimum alveolar concentration, isoflurane electroencephalogram burst suppression (EEG-BS), low-dose pentobarbital, pentobarbital EEG-BS, NBQX, conscious, and sham groups. AMPA 30 nm was injected into the cortex. An equivalent volume of cerebrospinal fluid was injected into the cortex in the sham group. In the NBQX group, 200 nm NBQX was injected into the cortex with the AMPA. In the isoflurane and pentobarbital groups, anesthesia was maintained for a period of 5 h. Animals in the conscious, NBQX, and sham groups were allowed to awaken immediately after the AMPA injection. Injury to the cortex was evaluated 48 h later.


RESULTS
Isoflurane reduced AMPA-induced cortical injury (4.5 +/- 1.9 mm3 and 1.7 +/- 0.8 mm3 in the 1 minimum alveolar concentration and EEG-BS groups, respectively) in comparison to the conscious group (7.2 +/- 0.8 mm3). Pentobarbital reduced cortical injury when administered in EEG-BS doses (2.2 +/- 0.7 mm3) but not when administered in sedative doses (8.6 +/- 0.9 mm3). NBQX reduced AMPA-induced cortical injury (1.2 +/- 0.5 mm3).


CONCLUSIONS
Isoflurane and pentobarbital reduced cortical AMPA excitotoxicity. The magnitude of injury reduction was similar to that produced by NBQX when the anesthetics were administered in EEG-BS doses. These results are consistent with the previously demonstrated ability of isoflurane and pentobarbital to inhibit AMPA receptor responses.
Kimbro
J R
JR
Department of Anesthesiology, University of California, VA Medical Center, San Diego 92161, USA.
Kelly
P J
PJ
Drummond
J C
JC
Cole
D J
DJ
Patel
P M
PM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018757:GABA Modulators / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007530:Isoflurane / Q000494:pharmacology*; D009336:Necrosis; D010424:Pentobarbital / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D018685:Anesthetics, Inhalation; D018690:Excitatory Amino Acid Agonists; D018757:GABA Modulators; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007530:Isoflurane; D010424:Pentobarbital