Affiliations: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Correspondence:
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Corresponding author: Yan-Yong Liu, Ph.D., and Ping-Ping Zuo, Ph.D., Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, No. 5 Dongdansantiao, Beijing 100005, China. Tel./Fax: +86 10 6915 6490; E-mail: [email protected] (Y.-Y. Liu); Tel./Fax: +86 10 6915 6404; E-mail: [email protected] (P.-P. Zuo).
Abstract:
Purpose: To investigate the effect and underlying mechanism of Aceglutamide on motor dysfunction in rats after cerebral ischemia-reperfusion.
Methods: Adult male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at 24 h after reperfusion and lasted for 14 days. Subsequently functional recovery was assessed and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by Western blot method. PC12 cells and primary cultured mesencephalic neurons were employed to further investigate the mechanism of Aceglutamide.
Results: Aceglutamide treatment improved behavioral functions, reduced the infarction volume, and elevated the number of TH-positive neurons in the SN. Moreover, Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile Aceglutamide treatment significantly inhibited the expression of TRAF1 and up-regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo.
Conclusions: Aceglutamide ameliorated motor dysfunction and delayed neuronal death in the SN after ischemia, which involved the inhibition of pro-apoptotic factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided experimental information for applying Aceglutamide to ischemic stroke treatment.
Keywords: Aceglutamide, neuroprotection, cerebral ischemia and reperfusion, motor function, substantia nigra, TNF receptor associated factor 1 (TRAF1), apoptosis
