Effects of mild hypothermia on the expression of microtubule-associated protein 2 in neurons of the hippocampal dentate gyrus in a rat model of cerebral ischemia/reperfusion*⋆

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It is widely accepted that mild hypothermia can protect against injury to cerebral ischemia/reperfusion.


To observe the effects of mild hypothermia on microtubule-associated protein 2 (MAP2) expression in the hippocampal dentate gyrus in rats following cerebral ischemia/reperfusion. Also, to study neuronal ultrastructural changes in the dentate gyrus to investigate the mechanism of the protection against injury to cerebral ischemia/reperfusion conferred by mild hypothermia.


This randomized grouping, neural cell morphology trial was performed at the Laboratory Animal Center of Yijishan Hospital between March and June 2007.


Eighty-five healthy male Sprague Dawley rats were randomly allocated to three groups: mild hypothermia (n = 40), normothermia (n = 40), and sham-operated (n = 5).


Cerebral ischemia/reperfusion injury was induced by the suture method in the mild hypothermia and normothermia groups, with a threading depth of 180.5 mm. In the sham-operated group, the suture was inserted 15 mm, with no vascular ligation, and was followed by reperfusion 2 hours later. In the sham-operated and normothermia groups, the rat rectal temperature was maintained at 36–37 °C; in the mild hypothermia group, it was controlled at 32–33 °C.


The hippocampal dentate gyrus was serially sectioned for hematoxylin-eosin staining and MAP2 immunohistochemistry. Ultrastructural changes and the MAP2 absorbance value of the hippocampal dentate gyrus were examined by transmission electron microscopy.


The sham-operated group exhibited approximately normal ultrastructure of neurons in the bilateral hippocampal dentate gyrus. In the normothermia group, ischemic hippocampal dentate gyrus neurons were found with markedly fewer normal mitochondria, greatly proliferated rough endoplasmic reticulum, and a swollen and dysmorphic Golgi. In the mild hypothermia group, at each corresponding time point, these abnormal changes were noticeably alleviated. The number of necrotic mitochondria, as well as the degree of degeneration, was obviously reduced compared with the normothermia group. At days 6, 8 and 10 following reperfusion, the normothermia group exhibited lower neurological function scores than the mild hypothermia group (P < 0.05). In the normothermia group, the absorbance value of MAP2 expression in the ischemic hippocampal dentate gyrus was significantly decreased compared with the sham-operated group (P < 0.01), was slightly increased at 4 days, and reached a peak on day 8. The mild hypothermia group showed an absorbance value of MAP2 expression in the ischemic hippocampal dentate gyrus similar to the normothermia group, but it reached a peak on day 6. On days 1, 2, 4 and 6 following reperfusion, MAP2 expression was lower in the mild hypothermia group than in the sham-operated group, but it was higher than the normothermia group (P < 0.05).


Mild hypothermia applied in early ischemia can alleviate brain injury. This may be due to an enhancement of MAP2 expression.

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