The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia.
The present study was undertaken to investigate the effects of the alpha2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus. Hemodynamic variables recorded during ischemia improved with clonidine treatment in both normo- and hyperglycemic groups. Glutamate and aspartate levels were greatly increased over control values during normo- and hyperglycemic NCFI treatment. Clonidine pretreatment suppressed the release of both glutamate and aspartate during NCFI in normo- and hyperglycemic rodents when compared with NCFI-treated normo- and hyperglycemic rats without the drug. Significant neuroprotection of cells in the cortex, striatum, and hippocampus was also observed in drug-treated animals 48 h postischemia. The combined effects of diminished glutamate release after NCFI and reduced neuronal injury in both normo- and hyperglycemic states suggests that clonidine treatment during NCFI is neuroprotective. The neuroprotective effect of clonidine during ischemia may be ascribed to both a sensitization of central sympathetic activity and a reduced release of glutamate thereby reducing NMDA receptor activation and neuronal damage.
Jellish
W Scott
WS
Department of Anesthesiology, Loyola University Medical Center, 2160 South First Ave., Maywood, IL 60153, USA. wjellis@lumc.edu
Murdoch
John
J
Kindel
Gisela
G
Zhang
Xin
X
White
Fletcher A
FA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000517:prevention & control; D016548:Prosencephalon / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014794:Visual Fields / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D003000:Clonidine