Ginsenoside Rb1 Promotes Motor Functional Recovery and Axonal Regeneration in Post-stroke Mice through cAMP/PKA/CREB Signaling Pathway

被引：52

作者：

Gao, Xuan ^{[1
]}

Zhang, Xiangjian ^{[1
,2
,3
]}

Cui, Lili ^{[1
,2
,3
]}

Chen, Rong ^{[1
,2
,3
]}

Zhang, Cong ^{[1
]}

Xue, Jing ^{[1
]}

Zhang, Lan ^{[1
]}

He, Weiliang ^{[1
]}

Li, Jiamin ^{[1
]}

Wei, Shanshan ^{[1
]}

Wei, Mengmeng ^{[1
]}

Cui, Hemei ^{[1
]}

机构：

[1] Hebei Med Univ, Dept Neurol, Hosp 2, 215 Hepingxi Rd, Shijiazhuang 050000, Hebei, Peoples R China

[2] Hebei Key Lab Vasc Homeostasis, 215 Hepingxi Rd, Shijiazhuang 050000, Hebei, Peoples R China

[3] Hebei Collaborat Innovat Ctr Cardiocerebrovasc Di, 215 Hepingxi Rd, Shijiazhuang 050000, Hebei, Peoples R China

来源：

BRAIN RESEARCH BULLETIN | 2020年 / 154卷

基金：

中国国家自然科学基金;

关键词：

Stroke; Ginsenoside Rb1; Axonal regeneration; cAMP; GAP43; H89; NEURAL STEM-CELLS; BEHAVIORAL RECOVERY; PERIINFARCT AREA; BRAIN-INJURY; CYCLIC-AMP; RAT MODEL; STROKE; GROWTH; CAMP; PLASTICITY;

D O I：

10.1016/j.brainresbull.2019.10.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The central nervous system (CNS) has a poor self-repairing capability after injury because of the inhibition of axonal regeneration by many myelin-associated inhibitory factors. Therefore, ischemic stroke usually leads to disability. Previous studies reported that Ginsenoside Rb1 (GRb1) plays a role in neuronal protection in acute phase after ischemic stroke, but its efficacy in post-stroke and the underlying mechanism are not clear. Recent evidences demonstrated GRb1 promotes neurotransmitter release through the cAMP-depend protein kinase A (PICA) pathway, which is related to axonal regeneration. The present study aimed to determine whether GRb1 improves long-term motor functional recovery and promotes cortical axon regeneration in post-stroke. Adult male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO). GRb1 solution (5 mg/ml) or equal volume of normal saline was injected intraperitoneally for the first time at 24 h after surgery, and then daily injected until day 14. Day 3, 7, 14 and 28 after dMCAO were used as observation time points. Motor functional recovery was assessed with Rota-rod test and grid walking task. The expression of growth-associated protein 43 (GAP43) and biotinylated dextran amine (BDA) was measured to evaluate axonal regeneration. The levels of cyclic AMP (cAMP) and PICA were measured by Elisa, PKAc and phosphorylated cAMP response element protein (pCREB) were determined by western blot. Our results shown that GRb1 treatment improved motor function and increased the expression of GAP43 and BDA in ipsilesional and contralateral cortex. GRb1 significantly elevated cAMP and PKA, increased the protein expression of PKAc and pCREB. However, the effects of GRb1 were eliminated by H89 intervention (a PKA inhibitor). These results suggested that GRb1 improved functional recovery in post-stroke by stimulating axonal regeneration and brain repair. The underlying mechanism might be up-regulating the expression of cAMP/PKA/CREB pathway.

引用

页码：51 / 60

页数：10

共 74 条

[1] Ginsenoside Rb1 as a neuroprotective agent: A review [J].