Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration after Stroke in Mice.
Ras-Related C3 Botulinum Toxin Substrate 1 Promotes Axonal Regeneration after Stroke in Mice.
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DOI：
10.1007/s12975-018-0611-5
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发表时间：
2018-10
影响因子：
6.9
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Liu L;Yuan H;Yi Y;Koellhoffer EC;Munshi Y;Bu F;Zhang Y;Zhang Z;McCullough LD;Li J
神经突可塑性是脑卒中后脑功能恢复的一个重要方面。新出现的数据表明，Ras相关的C3肉毒杆菌毒素底物1（Rac 1）在受损大脑的轴突再生中起着核心作用，特别是通过刺激神经元的内在生长和抵消生长抑制信号，导致生长锥崩溃。因此，我们研究了Rac 1在中风后轴突再生中的功能作用。延迟使用特定Rac 1抑制剂NSC 23766的治疗使功能恢复恶化，这通过卒中后第14天至第28天的颗粒到达试验进行评估。此外，在中风后28天评估，它还降低了梗死周围区的轴突密度，对脑腔大小或新形成细胞的数量没有影响。因此，使用慢病毒的Rac 1过表达促进了中风后第14天至第28天的轴突再生和功能恢复。Rac 1抑制导致促再生分子失活，包括在中风后14天的促分裂原活化蛋白激酶激酶（p-MEK）1/2、LIM结构域激酶（LIMK）1和细胞外信号调节激酶（p-ERK）1/2。抑制Rac 1减少轴突长度和数量在培养的原代小鼠皮质神经元使用微流控室后，氧-葡萄糖剥夺（OGD），而不影响细胞活力。相反，Rac 1的抑制增加了胶质细胞酸性蛋白的水平，轴突生长的外在抑制信号，在体内中风后和OGD后的原代星形胶质细胞。总之，Rac 1信号增强轴突再生，改善中风实验模型中风后的功能恢复。
Neurite plasticity is a critical aspect of brain functional recovery after stroke. Emerging data suggest that Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a central role in axonal regeneration in the injured brain, specifically by stimulating neuronal intrinsic growth and counteracting the growth inhibitory signaling that leads to growth cone collapse. Therefore, we investigated the functional role of Rac1 in axonal regeneration after stroke. Delayed treatment with a specific Rac1 inhibitor, NSC 23766, worsened functional recovery, which was assessed by the pellet reaching test from day 14 to day 28 after stroke. It additionally reduced axonal density in the peri-infarct zone, assessed 28 days after stroke, with no effect on brain cavity size or on the number of newly formed cells. Accordingly, Rac1 overexpression using lentivirus promoted axonal regeneration and functional recovery after stroke from day 14 to day 28. Rac1 inhibition led to inactivation of pro-regenerative molecules, including mitogen-activated protein kinase kinase (p-MEK)1/2, LIM domain kinase (LIMK)1, and extracellular signal-regulated kinase (p-ERK)1/2 at 14 days after stroke. Inhibition ofRac1 reduced axonal length and number in cultured primary mouse cortical neurons using microfluidic chambers after oxygen-glucose deprivation (OGD) without affecting cell viability. In contrast, inhibition of Rac1 increased levels of glial fibrillary acidic protein, an extrinsic inhibitory signal for axonal growth, after stroke in vivo and in primary astrocytes after OGD. In conclusion, Rac1 signaling enhances axonal regeneration and improve post-stroke functional recovery in experimental models of stroke.
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影响因子：
6.1
作者：
Benowitz LI;Carmichael ST
通讯作者：
Carmichael ST
影响因子：
4.3
作者：
Fujita Y;Yamashita T
通讯作者：
Yamashita T
延迟二十二碳六烯酸治疗结合膳食补充 Omega-3 脂肪酸可促进缺血性中风后长期神经血管恢复
影响因子：
6.9
作者：
Pu, Hongjian;Jiang, Xiaoyan;Hu, Xiaoming;Xia, Jinchao;Hong, Dandan;Zhang, Wenting;Gao, Yanqin;Chen, Jun;Shi, Yejie
通讯作者：
Shi, Yejie
影响因子：
2.4
作者：
Liu L;McCullough L;Li J
通讯作者：
Li J
影响因子：
6.2
作者：
Liu, Zhongwu;Li, Yi;Cui, Yisheng;Roberts, Cynthia;Lu, Mei;Wilhelmsson, Ulrika;Pekny, Milos;Chopp, Michael
通讯作者：
Chopp, Michael