Neuroprotection of naloxone against ischemic injury in rats: role of mu receptor antagonism.
Naloxone has been advanced as a potential neuroprotectant against ischemic injury. This study examined the involvement of classical opioid receptors in the reduction of middle cerebral arterial ligation-induced cortical infarction in rats. The infarct volume was significantly reduced after infusion of (-)-naloxone, but not its inert stereoisomer (+)-naloxone. Beta-funaltrexamine (beta-FNA), a mu opioid antagonist, also reduced ischemic infarct volume. Both (-)-naloxone and beta-FNA attenuated cerebral ischemia/reperfusion (I/R)-induced increases in neutrophil-associated myeloperoxidase activity and chemokine mRNA expression, including macrophage inflammatory protein-1 alpha and -2. However, (-)-naloxone and beta-FNA failed to decrease cerebral I/R-induced brain edema. The findings suggest that naloxone, acting through a blockade of mu opioid receptor activation, is beneficial to cerebral I/R insult in terms of reducing brain infarction, neutrophil accumulation, and chemokine expression.
Liao
Su-Lan
SL
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Chen
Wen-Yin
WY
Raung
Shue-Ling
SL
Chen
Chun-Jung
CJ
D000818:Animals; D017536:Carotid Artery, Common; D002544:Cerebral Infarction / Q000188:drug therapy / Q000209:etiology; D003327:Coronary Disease / Q000503:physiopathology; D007839:Functional Laterality; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000209:etiology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000502:physiology; D013997:Time Factors
D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine