title: Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia.
abstract: Mild hypothermia protects the brain against experimental ischemia, but the reasons are not well known. We examined whether the protective effects of mild hypothermia could be correlated with alterations in expression of Bcl-2, an anti-apoptotic protein in a rat model of transient global ischemia. Following 10 min of forebrain ischemia, hippocampal neurons were examined 72 h later for survival, expression of Bcl-2 family proteins and apoptosis. Intraischemic mild hypothermia was applied for 3 h (33 degrees C, isch-33) or normal body temperature was maintained (37 degrees C, isch-37). Survival of CA1 neurons was significantly improved in the isch-33 group compared to the isch-37 group (90 vs. 53% survival; P<0.01). The proportion of Bcl-2-positive cells among surviving CA1 neurons in the isch-33 group was increased compared to that of sham and isch-37 groups (P<0.01). Bax expression in CA1 was no different between sham and isch-33 groups, but was significantly decreased in isch-37 (P<0.05). TUNEL staining was positive in many isch-37 CA1 neurons, but absent in isch-33. Utilizing electron microscopy, more cells meeting criteria for apoptosis were observed in the isch-37 than isch-33. These data suggest that mild hypothermia attenuates apoptotic death, and that this protection may be related to increases in Bcl-2.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Rd. MSLS Building, P304, Stanford, CA 94305-5487, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: R A
authors.initials: RA
authors.lastname: Sobel
authors.forename: D
authors.initials: D
authors.lastname: Cheng
authors.forename: G K
authors.initials: GK
authors.lastname: Steinberg
authors.forename: M A
authors.initials: MA
authors.lastname: Yenari
mesh_terms: D000818:Animals; D001831:Body Temperature; D019938:Cyclin D1 / Q000378:metabolism*; D006361:Heating; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019938:Cyclin D1