Delayed moderate hypothermia reduces calpain activity and breakdown of its substrate in experimental focal cerebral ischemia in rats.
Calpains, intracellular proteases, are involved in various cerebral disorders. To determine the effect of moderate hypothermia on calpain activity, transient middle cerebral artery occlusion in rats was performed. For the reperfusion period normothermic temperature was compared to post-ischemic hypothermia (32 degrees C). Calpain expression was measured by Western blot analysis and immunohistochemistry. The loss of calpain substrate was determined by immunohistochemistry against the anti-microtubule-associated protein-2 (MAP-2). The increase of calpains in the ischemic as compared to the non-ischemic contralateral hemisphere and the loss of MAP-2 were reduced by hypothermia. These data indicate that calpain activity and calpain-induced proteolysis play an important role in the network of events following cerebral ischemia and can be reduced by hypothermia. Moderate hypothermia may be a useful tool to limit secondary injury induced by intracellular calpain degradation.
Liebetrau
Martin
M
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
Burggraf
Dorothe
D
Martens
Helge K
HK
Pichler
Mathias
M
Hamann
Gerhard F
GF
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D002154:Calpain / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013687:Telencephalon / Q000201:enzymology* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D008869:Microtubule-Associated Proteins; D010447:Peptide Hydrolases; D002154:Calpain