Post-ischemic hypothermia-induced tissue protection and diminished apoptosis after neonatal cerebral hypoxia-ischemia.
Hypothermia is possibly the single most effective method of neuroprotection developed to date. However, the mechanisms are not completely understood. The aim of this study was to investigate the effects of post-ischemic hypothermia on brain injury and apoptotic neuronal cell death as well as related biochemical changes after neonatal hypoxia-ischemia (HI). Seven-day-old rats were subjected to left common carotid artery ligation and hypoxia (7.8%) for 1 h. Systemic hypothermia was induced immediately after hypoxia-ischemia, and body temperature was maintained at 30 degrees C for 10 h. The normothermic group was kept at 36 degrees C. Brain infarct volumes and neuronal loss in the CA1 area of the hippocampus were significantly reduced at 72 h post-HI in the hypothermia group. Cytochrome c release and activation of caspase-3 and -2 at 24 h post-HI were significantly diminished by hypothermia. The numbers of cytochrome c- and TUNEL-positive cells in the cortex and dentate gyrus of the hippocampus were significantly reduced in the hypothermia group compared with the normothermia group at 72 h post-HI. These results indicate that hypothermia may, at least partially, act through inhibition of the intrinsic pathway of caspase activation in the neonatal brain, thereby preventing apoptotic cell death.
Zhu
Changlian
C
Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, PR China. changlianzhu@hotmail.com
Wang
Xiaoyang
X
Cheng
Xiuyong
X
Qiu
Lin
L
Xu
Falin
F
Simbruner
George
G
Blomgren
Klas
K
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001831:Body Temperature / Q000502:physiology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D007839:Functional Laterality; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008869:Microtubule-Associated Proteins; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D020169:Caspases