Korean J Crit Care Med.  2007 Jun;22(1):30-41.

The Effects of Mild Hypothermia on the Expression of the Apoptosis-related Proteins following Transient Global Ischemia in Gerbil Hippocampus

Affiliations
  • 1Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Korea. emart@catholic.ac.kr
  • 2Department of Surgery, Kangnam CHA General Hospital, Pochon CHA University, Seoul, Korea.

Abstract

BACKGROUND
The neuroprotective mechanisms of hypothermia remain unclear. Recently, attenuation of apoptosis by hypothermia has been suggested as one of the responsible mechanisms. The aim of this study is to investigate the effects of post-ischemic hypothermia on apoptotic neuronal death as well as expression of some apoptosis-related proteins in a gerbil transient global ischemia model. METHODS: Following 5 minutes of ischemia, normothermia (NT, 37+/-0.5degrees C) or mild hypothermia (HT, 33+/-0.5degrees C) was immediately induced and maintained for 3 hours. The hippocampal CA1 neurons were examined on day 2, 3, 4, and 7 after ischemia for the survived neuronal densities, DNA nick end labeling and immunohistochemical expressions of Bcl-2, Bax, and caspase 3 in each group. Additionally, DNA gel electrophoresis and western blot analysis for each protein in hippocampus were performed. RESULTS: The neuronal death in CA1 area on day 3, 4, and 7 was significantly reduced in HT group compared to NT group. The number of TUNEL positive cells in HT group was also significantly reduced than NT group on day 3, 4, and 7. DNA laddering of hippocampus on day 4 and 7 also reduced in HT group. Expressions of Bax on days 2, 3 and activated caspase 3 on days 3, 4 were reduced in HT group. Western blots also disclosed a decrease in the intensity of the Bax on day 2 and 3 in HT group compared to NT group. CONCLUSIONS: These results suggest that mild post-ischemic hypothermia attenuates the apoptotic neuronal death through the inhibition of the intrinsic pathway of caspase activation following transient global ischemia and these effects may be related to a reduction of pro-apoptotic events.

Keyword

Bax; Bcl-2; Caspase 3; Post-ischemic hypothermia; Transient global ischemia

MeSH Terms

Apoptosis
Blotting, Western
Caspase 3
DNA
DNA Breaks, Single-Stranded
Electrophoresis
Gerbillinae*
Hippocampus*
Hypothermia*
In Situ Nick-End Labeling
Ischemia*
Neurons
Caspase 3
DNA
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