Neuroprotection role of adenosine under hypothermia in the rat global ischemia involves inhibition of not dopamine release but delayed postischemic hypoperfusion.
Adenosine (ADO) has an important role in the ischemic brain as an endogenous neuroprotective factor. On the other hand, intraischemic hypothermia ameliorates ischemic neuronal injury. To investigate the effect of ADO during intraischemic mild hypothermia, the extracellular concentration of ADO, its metabolites, dopamine (DA), and local cerebral blood flow were measured in rat striatum during and after 20 min of global ischemia. Additionally, the histopathological outcome was estimated after 48 h of recirculation. Three experimental groups were used: (1) a normothermic group (NT) maintained at 37 degrees C during and after ischemia; (2) a hypothermic group (HT), exposed to intraischemic hypothermia (32.0 degrees C) and postischemic normothermia; and (3) a hypothermia plus theophylline group (HT+T), with the same temperature conditions as in the HT group, combined with intravenously administration of theophylline (10 mg/kg), an antagonist of adenosine receptor, which was given 10 min before ischemia. The level of ADO in HT was significantly higher than ADO levels in NT. In contrast, ischemic DA release was significantly inhibited in HT compared with NT. Theophylline administration had no effect on intraischemic hypothermia induced modulation of extracellular ADO and DA concentration. The postischemic delayed hypoperfusion was ameliorated in HT, and theophylline eliminated this effect in HT+T. A protective effect on histopathological outcome was observed in HT and HT+T. These results suggest that ADO plays an essential role in the inhibition of postischemic delayed hypoperfusion, but this effect is not crucial role in the protective effect induced by intraischemic hypothermia.
Horiguchi
Takashi
T
Department of Neurosurgery, School of Medicine, Keio University, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan. tghorigu@wfubmc.edu
Shimizu
Katsuyoshi
K
Ogino
Masahiro
M
Yamaguchi
Noriyuki
N
Suga
Sadao
S
Inamasu
Joji
J
Kawase
Takeshi
T
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000379:methods
D018696:Neuroprotective Agents; D000241:Adenosine; D004298:Dopamine