Activation of cerebral Ras-related C3 botulinum toxin substrate (Rac) 1 promotes post-ischemic stroke functional recovery in aged mice.
Activation of cerebral Ras-related C3 botulinum toxin substrate (Rac) 1 promotes post-ischemic stroke functional recovery in aged mice.
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激活脑ras相关C3肉毒毒素底物（Rac） 1促进老年小鼠缺血性卒中后功能恢复。
DOI：
10.4103/1673-5374.382256
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发表时间：
2024-04
影响因子：
6.1
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Bu F;Min JW;Razzaque MA;El Hamamy A;Patrizz A;Qi L;Urayama A;Li J
Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged (male, 18 to 22 months old C57BL/6J) brain after ischemic stroke. We found that as mice aged, Rac1 expression declined in the brain. Delayed overexpression of Rac1, using lentivirus encoding Rac1 injected day 1 after ischemic stroke, promoted cognitive (assessed using novel object recognition test) and sensorimotor (assessed using adhesive removal tests) recovery on days 14–28. This was accompanied by the increase of neurite and proliferative endothelial cells in the peri-infarct zone assessed by immunostaining. In a reverse approach, pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells. Furthermore, Rac1 inhibition reduced the activation of p21-activated kinase 1, the protein level of brain-derived neurotrophic factor, and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke. Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
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影响因子：
20.3
作者：
Mizukawa, Benjamin;Wei, Junping;Mulloy, James C.
通讯作者：
Mulloy, James C.
影响因子：
11
作者：
Finger, Carson E.;Moreno-Gonzalez, Ines;Gutierrez, Antonia;Moruno-Manchon, Jose Felix;McCullough, Louise D.
通讯作者：
McCullough, Louise D.
RAC1-PAK1 RAB11循环的调节促进了连接处的稳定化。
DOI：
10.1083/jcb.202002114
发表时间：
2021-06-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Erasmus JC;Smolarczyk K;Brezovjakova H;Mohd-Naim NF;Lozano E;Matter K;Braga VMM
通讯作者：
Braga VMM
影响因子：
7.8
作者：
Jin, KL;Minami, M;Greenberg, DA
通讯作者：
Greenberg, DA
DOI：
10.1124/jpet.113.207266
发表时间：
2013-10-01
影响因子：
3.5
作者：
Levay, Magdolna;Krobert, Kurt Allen;Wieland, Thomas
通讯作者：
Wieland, Thomas