Neuroprotective effects of Aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion.

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.

• Authors: Rui Zhang, Nan Yang, Chao Ji, Ji Zheng, Zhen Liang, Chun-Ying Hou, Yan-Yong Liu, Ping-Ping Zuo
• Journal: Restorative neurology and neuroscience (Restor Neurol Neurosci) Vol. 33 Issue 5 Pg. 741-59 ( 2015) ISSN: 1878-3627 [Electronic] Netherlands
• PMID: 26444640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• aceglutamide
• Glutamine

Topics

• Animals
• Brain Ischemia (drug therapy, pathology)
• Cell Death (drug effects, physiology)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Glutamine (analogs & derivatives, chemistry, pharmacology)
• Infarction, Middle Cerebral Artery
• Injections, Intraperitoneal
• Male
• Mesencephalon (drug effects, metabolism, pathology)
• Movement Disorders (drug therapy, pathology, physiopathology)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (chemistry, pharmacology)
• PC12 Cells
• Rats
• Rats, Sprague-Dawley
• Substantia Nigra (drug effects, metabolism, pathology)
• Treatment Outcome