Journal article
Relative Neuroprotective Effects of Dizocilpine and Isoflurane During Focal Cerebral Ischemia in the Rat
Anesthesia and analgesia, Vol.87(1), pp.72-78
1998
DOI: 10.1097/00000539-199807000-00016
PMID: 9661549
Abstract
Both dizocilpine (MK-801) and isoflurane antagonize glutamatergic neurotransmission. In this study, we examined the relative neuroprotective effects of these drugs administered in equianesthetic doses before the onset of focal cerebral ischemia. Rats were anesthetized with 1.0%-1.5% isoflurane and surgically prepared for filament occlusion of the middle cerebral artery (MCAO). After preparation, one group (n = 22) remained anesthetized with 0.7% isoflurane. Another group (n = 18) was given dizocilpine (1 mg/kg intraperitoneally), and isoflurane was discontinued. The third group (n = 18) was allowed to awaken immediately after the onset of ischemia. MCAO persisted for 75 min. Epidural temperature was controlled at 37.5[degree sign]C during ischemia and the first 22 h of recovery. A 7-day recovery interval was allowed. Total infarction volumes (mean +/- SD) were less for the dizocilpine group (100 +/- 65 mm) versus the awake group (182 +/- 36 mm; P = 0.001). Infarction volumes did not differ significantly between the isoflurane group (142 +/- 81 mm) and either the dizocilpine (P = 0.11) or the awake group (P = 0.15). Isoflurane was examined at doses used clinically but smaller than those found to reduce N-methyl-D-aspartate (NMDA)-mediated injury in vitro. This study supports the hypothesis that NMDA receptor activation is injurious during focal ischemia and that amelioration of focal ischemic brain damage by NMDA receptor antagonists persists under normothermic conditions. ImplicationsRats underwent focal cerebral ischemia with rigid maintenance of brain normothermia. The glutamate receptor antagonist dizocilpine was effective in reducing cerebral infarction size during persistent conditions of brain normothermia. In contrast, isoflurane administered at equianesthetic doses did not reduce infarction size. This study supports the hypothesis that N-methyl-D-aspartate receptor activation is injurious during focal ischemia and that amelioration of focal ischemic brain damage by N-methyl-D-aspartate receptor antagonists persists under normothermic conditions.(Anesth Analg 1998;87:72-8)
Details
- Title: Subtitle
- Relative Neuroprotective Effects of Dizocilpine and Isoflurane During Focal Cerebral Ischemia in the Rat
- Creators
- Shiva Sarraf-Yazdi - Duke University School of MedicineHuaxin Sheng - Duke University HospitalYoshihide Miura - Duke University HospitalClaude McFarlane - University of North Carolina at Chapel HillFranklin DexterRobert D PearlsteinDavid S Warner - Duke University Hospital
- Resource Type
- Journal article
- Publication Details
- Anesthesia and analgesia, Vol.87(1), pp.72-78
- Publisher
- International Anesthesia Research Society; PHILADELPHIA
- DOI
- 10.1097/00000539-199807000-00016
- PMID
- 9661549
- ISSN
- 0003-2999
- eISSN
- 1526-7598
- Number of pages
- 7
- Grant note
- R01 GM39771-11 / NIGMS NIH HHS
- Language
- English
- Date published
- 1998
- Academic Unit
- Anesthesia
- Record Identifier
- 9983806261302771
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