Attenuation of Cell Death in Injured Cortex After Post-Traumatic Brain Injury Moderate Hypothermia: Possible Involvement of Autophagy Pathway
Attenuation of Cell Death in Injured Cortex After Post-Traumatic Brain Injury Moderate Hypothermia: Possible Involvement of Autophagy Pathway
复制标题
创伤后脑损伤中度低温后受损皮质中细胞死亡的减弱：自噬途径的可能参与。
DOI：
10.1016/j.wneu.2015.03.039
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发表时间：
2015-08-01
影响因子：
2
通讯作者：
Jiang, Ji-Yao
中科院分区：
文献类型：
--
作者：
Jin, Yichao;Lin, Yingying;Jiang, Ji-Yao
目的：探讨液体撞击性脑损伤（TB!）后细胞死亡的多种机制。在本研究中，我们评估了液体冲击脑损伤后对损伤皮质细胞死亡的影响，并探讨了自噬的可能作用。方法：采用液体冲击式脑损伤装置建立脑损伤模型。在全身麻醉下，局部浸入水浴（0℃）4小时，达到中度低温（32℃）。所有大鼠均于脑外伤后6、24小时处死。结果：经Western blotting检测的Cleaved caspase 3和末端脱氧胆碱转移酶介导的2’-脱氧尿苷5’-三磷酸生物素缺口末端标记阳性细胞在液体冲击TBI后6小时显著增加，并在TB后24小时进一步上调！， Beclin-1和蛋白轻链-3的表达水平也显著上调。低温4小时后，观察到自噬生物标志物进一步上调，caspase 3上调减弱，细胞死亡减少。免疫荧光细胞定位分析显示，低温处理后脑损伤皮层中蛋白轻链3-和beclin -1阳性细胞包括神经元和胶质细胞。超微结构观察发现，损伤后6、24小时脑组织皮层自溶酶体显著升高，低温处理后脑组织皮层自溶酶体进一步上调。结论：这些数据表明，低温处理可能通过激活自噬途径来减轻TBI诱导的液体冲击TBI模型细胞死亡。
OBJECTIVE: Multiple mechanisms participated hi the cell death after fluid percussion traumatic brain injury (TB!). In the present study, we evaluated the effect on cell death in the injured cortex after fluid percussion TBI and investigated a possible role of autophagy.METHODS: TBI model was induced by a fluid percussion TBI device. Moderate hypothermia (32 degrees C) was achieved by partial immersion in a water bath (0 degrees C) under general anesthesia for 4 hours. All rats were killed at 6 or 24 hours after TBI.RESULTS: Cleaved caspase 3 evaluated with Western blotting and terminal deoxynincleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive cells in injured cortex were significantly increased 6 hours after fluid percussion TBI and were further up-regulated 24 hours after TB!, dramatic up-regulation of Beclin-1 and protein light chain-3 expression levels was also observed. Further up-regulation of biomarkers of autophagy, attenuation of caspase 3 up-regulation and reduction of cell death was observed after 4 hours of hypothermia. Immunofluorescence analysis for cell localization demonstrated that protein light chain-3- and Beclin-1-positive cells included neurons and glial cells in the injured cortex after TBI and hypothermic treatment. By ultrastructural observation, autolysosomes in injured cortex were significantly increased at 6 and 24 hours after TBI and were further up-regulated after TBI hypothermic treatment.CONCLUSIONS: These data suggest that hypothermic treatment could attenuate TBI-induced cell death in this fluid percussion TBI model, possibly through activation of autophagy pathway.