Fastigial nucleus electrostimulation promotes axonal regeneration after experimental stroke via cAMP/PKA pathway
Fastigial nucleus electrostimulation promotes axonal regeneration after experimental stroke via cAMP/PKA pathway
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顶核电刺激通过 cAMP/PKA 途径促进实验性卒中后轴突再生
DOI：
10.1016/j.neulet.2019.02.016
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发表时间：
2019-04-23
影响因子：
2.5
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Wang, An-rong;Hu, Ming-zhe;Liu, Bin
哺乳动物脑缺血后的轴突再生不足以恢复功能，这表明需要设计更好的策略来改善结果。在动物实验中，通过顶核电刺激（FNS）实现了轴突再生的改善。然而，这种神经保护的机制仍然知之甚少。增加第二信使环AMP （cAMP）的水平可增强轴突再生，使其成为具有治疗潜力的优秀候选分子。在本研究中，我们检测了局灶性脑缺血后缺血脑组织中cAMP信号的表达。采用脑中动脉闭塞（MCAO）对成年大鼠进行缺血治疗。将偶极电极置入小脑，对缺血后的小脑顶状核刺激1小时。测定神经功能缺损及cAMP、PKA（蛋白激酶A）和ROCK （rho激酶）的表达。通过上调生长相关蛋白43 （GAP43）来测量轴突再生。结果表明，FNS可显著促进脑缺血后的轴突再生和运动功能恢复。FNS还能显著提高缺血性脑损伤后cAMP和PKA水平。FNS的所有有益作用均被PKA拮抗剂Rp-cAMP阻断。本研究提示FNS诱导的轴突再生可能是通过cAMP/PKA通路调控实现的。
Axon regeneration after cerebral ischemia in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Improvement of axon regeneration has been achieved through fastigial nucleus electrostimulation (FNS) in animal researches. However, the mechanisms underlying this neuroprotection remain poorly understood. Increasing the levels of the second messenger cyclic AMP (cAMP) enhances axon regeneration, making it an excellent candidate molecule that has therapeutic potential. In the present study, we examined the expression of cAMP signaling in ischemic brain tissues following focal cerebral ischemia. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion (MCAO). A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h after ischemia. Neurological deficits and the expressions of cAMP, PKA (protein kinase A) and ROCK (Rho-kinase) were determined. Axonal regeneration was measured by upregulation of growth-associated protein 43 (GAP43). The data indicated that FNS significantly enhanced axonal regeneration and motor function recovery after cerebral ischemia. FNS also significantly increased cAMP and PKA levels after ischemic brain injury. All the beneficial effects of FNS were blocked by Rp-cAMP, an antagonist of PKA. Our research suggested that the axonal regeneration conferred by FNS was likely achieved via the regulation of cAMP/PKA pathway.