Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats.
Hypothermia confers potent neuroprotection against ischemic injury. Attenuation of apoptosis by hypothermia can be one of the responsible mechanisms. In this study, in situ DNA nick-end labeling (TUNEL) and immunostaining of Bax protein were performed to evaluate the effect of postischemic hypothermia on apoptotic cell death, employing rodent transient focal ischemia. Animals received 1 hour of transient focal ischemia. Brain temperature was maintained at 37.5 +/- 0.5 degrees C during ischemia. Immediately after reperfusion, animals were assigned to either a normothermic or hypothermic group. In hypothermia, animals were cooled and brain temperature was lowered to 34.5 +/- 1.0 degrees C. Prolonged hypothermia was maintained for 16 hours and animals rewarmed. In both groups, TUNEL and immunostaining of Bax was performed. In normothermia, the number of TUNEL positive cells reached the peak at 2 days after ischemia and decreased gradually. In hypothermia, the peak was shifted to 3 days after ischemia. The number of TUNEL positive cells in hypothermia was persistently below that of normothermia. Similarly, in hypothermia, immunostaining of Bax showed attenuated immunoreactivity compared with that in normothermia. In conclusion, postischemic hypothermia reduced both the number of TUNEL positive cells and immunoreactivity of Bax, which may be one of the responsible mechanisms with which hypothermia exerts neuroprotection.
Inamasu
J
J
Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
Suga
S
S
Sato
S
S
Horiguchi
T
T
Akaji
K
K
Mayanagi
K
K
Kawase
T
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000473:pathology*; D007036:Hypothermia, Induced; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein