Li Xin, Zheng Wei, Bai Hongying, Wang Jin, Wei Ruili, Wen Hongtao, Ning Hanbing
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Nursing, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Neuropsychiatr Dis Treat. 2016 Jun 2;12:1287-93. doi: 10.2147/NDT.S104917. eCollection 2016.
Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs) transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF-TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO) rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats.
先前的研究已表明脂肪干细胞(ADSCs)移植对中风具有有益作用。然而,移植的ADSCs促进神经愈合的分子机制尚未阐明。因此,为了明确ADSCs神经保护作用的分子机制并研究BDNF-TrkB信号通路在ADSCs神经保护中的作用,我们检测了接受或未接受ADSCs移植的大脑中动脉闭塞(MCAO)大鼠的神经功能、脑含水量及蛋白表达情况。在MCAO后30分钟经静脉将ADSCs移植入大鼠体内。通过脑室内和脑立体定向注射将TrkB抑制剂K252a给予大鼠。采用改良神经功能缺损评分测试来衡量行为结果。结果显示,ADSCs显著减轻了MCAO大鼠的神经功能缺损并降低了脑含水量。经ADSCs治疗的MCAO大鼠皮质中BDNF和TrkB的蛋白表达水平显著升高。然而,给予K252a可逆转ADSCs诱导的MCAO大鼠中BDNF、TrkB和Bcl-2的升高以及Bax蛋白的降低。ADSCs通过TrkB信号通路促进BDNF表达并改善中风大鼠的神经功能恢复。