Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease.
Neuroprotective mechanisms of hypothermia have not been clearly established especially in the immature brain. To investigate the effect of hypothermia on cell death and cell survival signal pathways, we studied caspase-3-like activity and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at 37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho-Akt was increased during the early reperfusion period after H-I in the normothermia group, but hypothermia rather decreased this enhanced phosphorylation of Akt following H-I. These results indicated that hypothermia may have some depressant effects on both cell death and cell survival signal pathways, and that Akt conceivably may not play a major role in the neuroprotective effect of hypothermia in the immature brain.
Tomimatsu
T
T
Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. tomimatu@gyne.med.osaka-u.ac.jp
Fukuda
H
H
Endo
M
M
Watanabe
N
N
Mu
J
J
Kohzuki
M
M
Fujii
E
E
Kanzaki
T
T
Murata
Y
Y
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001238:Asphyxia Neonatorum / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D001831:Body Temperature; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000503:physiopathology / Q000628:therapy; D007231:Infant, Newborn; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology; D013687:Telencephalon / Q000201:enzymology / Q000293:injuries / Q000503:physiopathology
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases