Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration.
Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration.
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DOI：
10.1038/s41598-017-03792-9
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Pick CG
中科院分区：
文献类型：
--
作者：
Rachmany L;Tweedie D;Rubovitch V;Li Y;Holloway HW;Kim DS;Ratliff WA;Saykally JN;Citron BA;Hoffer BJ;Greig NH;Pick CG
轻度冲击波创伤性脑损伤(B-TBI)导致新物体识别的持久认知障碍和Y-迷宫行为的较轻缺陷。B-TBI可显著降低大脑皮质(CTX)和海马区(HIPP)突触素(SYP)蛋白染色水平。创伤性脑损伤前48 小时或伤后2 小时皮下注射Exendin-4(Ex-4)可预防认知功能障碍和脑损伤后SYP染色的改变。在体外颅脑损伤模型中，研究了一系列双轴拉伸损伤(BSI)对神经源性细胞系HT22细胞的影响。双轴拉伸损伤可导致轴突萎缩和细胞死亡。在损伤前用Ex-4(25~100 NM)处理HT22细胞，可减弱BSI的细胞毒性作用，并保留与假处理细胞相似的轴突长度。这些数据表明，使用Ex-4治疗可能是处理由爆炸诱发的轻微创伤性脑损伤引发的继发性事件的可行选择，这种情况在军事化地区很常见。
Mild blast traumatic brain injury (B-TBI) induced lasting cognitive impairments in novel object recognition and less severe deficits in Y-maze behaviors. B-TBI significantly reduced the levels of synaptophysin (SYP) protein staining in cortical (CTX) and hippocampal (HIPP) tissues. Treatment with exendin-4 (Ex-4) delivered by subcutaneous micro-osmotic pumps 48 hours prior to or 2 hours immediately after B-TBI prevented the induction of both cognitive deficits and B-TBI induced changes in SYP staining. The effects of a series of biaxial stretch injuries (BSI) on a neuronal derived cell line, HT22 cells, were assessed in an in vitro model of TBI. Biaxial stretch damage induced shrunken neurites and cell death. Treatment of HT22 cultures with Ex-4 (25 to 100 nM), prior to injury, attenuated the cytotoxic effects of BSI and preserved neurite length similar to sham treated cells. These data imply that treatment with Ex-4 may represent a viable option for the management of secondary events triggered by blast-induced, mild traumatic brain injury that is commonly observed in militarized zones.