Dantrolene ameliorates delayed cell death and concomitant DNA fragmentation in the rat hippocampal CA1 neurons subjected to mild ischemia.
The present study investigated whether dantrolene, which inhibits the Ca(2+) release from the intracellular Ca(2+) store sites, reduced nuclear DNA fragmentation and produced neuronal protection in a model of global forebrain ischemia. Male Wistar rats were subjected to four-vessel occlusion (4VO) for 5 min and then infused continuously with dantrolene or vehicle into the cerebral ventricle for 3 days. The intact rats did not undergo any intervention. The number of viable and DNA nick-end-labeled neurons in the hippocampal CA1 were evaluated 4 days after the ischemia. The number of viable neurons in the dantrolene-treated rats was significantly higher than that in the vehicle-treated rats and lower than that in the intact animals (P<0.01 and <0.05, respectively). The number of DNA nick-end-labeled nuclei was significantly lower in dantrolene-treated rats compared with the vehicle-treated animals (P<0.0001). No nick-end labeling was observed in the intact animals. A linear correlation was found between the number of viable cells and nick-end labeled nuclei in the CA1 (r=0.91, P<0.0001). These results suggest that the postischemic intraventricular dantrolene is effective in precluding neuronal death and concomitant nuclear DNA fragmentation following transient global ischemia.
Yano
T
T
Surgical Center, Kumamoto University Hospital, Kumamoto 860-8556, Japan. tymac@kaiju.medic.kumamoto-u.ac.jp
Nakayama
R
R
Imaizumi
T
T
Terasaki
H
H
Ushijima
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000473:pathology*; D053938:DNA Fragmentation / Q000187:drug effects*; D003620:Dantrolene / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009125:Muscle Relaxants, Central; D003620:Dantrolene