Title: Effect of autophagy on recovery of neurological dysfunction in rats after cerebral ischemia-reperfusion injury
Abstract: Objective
To observe the development and progression of autophagy, and investigate the effect of autophagy on recovery of neurological dysfunction in rats after cerebral ischemia-reperfusion injury.
Methods
Preparation of middle cerebral artery occlusion (MCAO) models was performed by Longa method. (1) Forty-two SD rats were randomly assigned to blank control 1 group (n=9) and MCAO 1 group (n=33), and the rats of the MCAO 1 group were randomly divided into 6, 12, 48 and 72 h subgroups (n=6) and 24 h subgroup (n=9) according to the reperfusion times; the ultrastructural changes and autophagosome formation in hippocampal tissues of the blank control 1 group (n=3) and 24-h-reperfusion MCAO 1 subgroup (n=3) were observed under transmission electron microscope; the expressions of microtubule associated proteins light chain-3 (LC3)-II, LC3-I and Beclin-1 in the hippocampal tissues of each group (n=6) were detected by Western blotting. (2) Eighteen SD rats were randomly divided into blank control 2 group, MCAO 2 group and 3-methyladenine (3-MA, autophagy inhibitor) group (60 min prior to MCAO, injection of 10 μL [600 nmoL] 3-MA dilution into the lateral ventricle by stereotactic technique, n=6); the neurological rehabilitation of rats was analyzed by modified neurological severity scale (mNSS) one, 3, 5 and 7 d after reperfusion; the morphological changes and number of apoptotic cells in the hippocampal tissues were observed by HE staining 7 d after reperfusion.
Results
(1) The formation of autophagy in the 24-h-reperfusion MCAO 1 subgroup was clearly observed under microscope; as compared with blank control 1 group, the ratio of LC3-II/I (excepted for 72-h-reperfusion MCAO 1 subgroup) and Beclin-1 expression in the hippocampus of 6, 12, 24 and 48-h-reperfusion MCAO 1 subgroups were significantly increased (P<0.05); as compared with those in the 24-h-reperfusion MCAO 1 subgroup, the ratio of LC3-II/I and Beclin-1 expression in the hippocampus of 6, 12, 48 and 72-h-reperfusion MCAO 1 subgroups were significantly decreased (P< 0.05). (2) As compared with those the MCAO 2 group, the mNSS scores of 3-MA group were significantly decreased 3, 5 and 7 d after surgery (P<0.05); HE staining indicated that the injury of neurons in the hippocampus of 3-MA group was alleviated, and the number of apoptotic cells in the 3-MA group was significantly smaller than that in the MCAO 2 group ([14.00±2.10]/field vs. [37.83±2.64]/field, P<0.05).
Conclusion
Cerebral ischemia-reperfusion injury can activate autophagy, by which it can alleviate brain damage and improve its neurological dysfunction in rats after cerebral ischemia-reperfusion injury.
Key words:
Cerebral ischemia reperfusion injury; Autophagy; Neurological dysfunction
Publication Year: 2018
Publication Date: 2018-02-15
Language: en
Type: article
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