Effect of autophagy response on neurological functions and its mechanism in rats after traumatic brain injury
10.3760/cma.j.issn.1671-8925.2016.12.003
- VernacularTitle:自噬反应对大鼠创伤性颅脑损伤后神经功能的影响及机制研究
- Author:
Xiangrong CHEN
1
;
Zhihui TANG
;
Yasong LI
;
Qinliang LUO
;
Weipeng HU
;
Chaoyang XU
Author Information
1. 福建医科大学第二附属医院神经外科
- Keywords:
Traumatic brain injury;
Neuroprotection;
Autophagy;
Mitogen-activated protein kinase signaling pathway
- From:
Chinese Journal of Neuromedicine
2016;15(12):1200-1205
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of autophagy response on neurological functions and the role of mitogen-activated protein kinases (MAPKs) signaling pathway in rats after traumatic brain injury (TBI).Methods Fifty-four healthy male SD rats were randomly divided into sham-operated group,TBI group and TBI+autophagy inhibitor 3-methyladenine (3-MA) group (n=18).TBI animal models of the later two groups were established using Feeney's method.Rats in the sham-operated group were only performed bone window opening without knock;rats in the TBI+3-MA group were given intraperitoneal injection of 3-MA(5 mg/kg) 30 min after modeling and rats in the other two groups were given the same volume of normal saline.Three and 7 d after modeling,the protein levels of S100B and neuron specific enolase (NSE) in serum were tested with enzyme linked immunosorbent assay (ELISA);modified neurologic severity scale (mNSS) was used to detect the movement,sense and reflex functions;brain water content was measured with wet-dry weight method.The autophagy related factors (LC3-Ⅱ and Beclin-1) and MAPKs signaling pathway related factors (c-Jun N-terminal kinase [JNK],phosphorylated [p]-JNK,extracellular signal-regulated kinase [ERK]1/2,p-ERK1/2,p38MAPK and p-p38MAPK) protein expressions in TBI cerebral cortex were determined by Western blotting.Results As compared with those in the sham-operated group,the brain edema level,mNSS scores,and S100B and NSE protein levels in the TBI group and TBI+3-MA group were significantly increased (P＜0.05);TBI+3-MA group had significantly lower brain edema level,mNSS scores,and S100B and NSE protein levels than TBI group (P＜0.05).The expression levels of autophagy and MAPKs signaling pathway related factors in the TBI group and TBI+3-MA group were significantly higher as compared with those in the sham-operated group (P＜0.05).As compared with the TBI group,TBI+3-MA group had significantly decreased levels of LC3-Ⅱ,Beclin-1 and activation of JNK and p-p38MAPK signaling pathways (P＜0.05).Conclusion Suppressing autophagy response markedly improves neurological outcomes after TBI,possibly mediated by inhibiting activation of JNK and p38MAPK signaling pathways.
