Effects of monochlorobimane on cerebral ischemia-induced damage to mitochondria.
A possible involvement of inhibitory effects of monochlorobimane (MCB) on the opening of mitochondrial permeability transition (MPT) pore in the cerebroprotection against the ischemic brain injury was examined. MCB (1 mM) inhibited the opening of MPT pore in vitro. Sustained cerebral ischemia was induced by injecting 900 microspheres (48 microm in diameter) into the right hemisphere of rats. At 12 to 72 h after microsphere embolism (ME), the mitochondrial activity was determined histochemically by staining cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) of the brain sections. The COX and SDH stainings in the hippocampus were observed intensively in the pyramidal neurons in the CA2-3 and dentate gyrus rather than those in the CA-1 region. The staining was decreased with time after the embolism. Pretreatment with 10 microg/animal MCB 30 min prior to the embolism significantly attenuated the ME-induced reduction in the staining of COX and SDH in the hippocampus, but not in the pariatal cortex. The results suggest that prevention of the opening of MPT pore by MCB may play an important role in the cerebroprotection against cerebral ischemic injury.
Oshikawa
Sayuri
S
Department of Pharmacology, Tokyo University of Pharmacy & Life Science, Hachioji, Tokyo 192-0392, Japan.
Miyake-Takagi
Keiko
K
Takagi
Norio
N
Abe
Tsutomu
T
Kuruhara
Yoshitada
Y
Takeo
Satoshi
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003576:Electron Transport Complex IV / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D008297:Male; D008863:Microspheres; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011720:Pyrazoles; C059597:monochlorobimane; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV