Original Research

NSC23766, A Specific Inhibitor of Rac1 GTPase, Attenuated Delayed Neuronal Cell Death and Cognitive Deficit in Rats with Cardiac Arrest

Juan Liao , Chang Xu , Chang Liu , Na Wang , Guo-Qing Huang , Chang-Sheng Huang , Zhi Ye , Qu-Lian Guo
Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China, Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Department of Emergency, Xiangya Hospital, Central South University, Changsha, China
J Anesth Perioper Med 2015; 2(3): 136- 145 . Published on May 1, 2015 . doi:10.24015/JAPM.2015.0019
Abstract
Article
Figures & Tables
References
Author & Article info
PDF

Abstract

Background: Recent studies have implicated that inhibition of Rac1 GTPase protects the neuronal cells from cerebral ischemic injury, although its effects in a cardiac arrest (CA) global cerebral ischemia model have not been examined. The purpose of the current study was to examine the regulatory and functional role of the Rac1 in reactive oxygen species (ROS) generation and neuronal cell death/cognitive dysfunction following global cerebral ischemia in the rats.

Methods: A rat model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Rats were randomly assigned to the following groups: 1) sham group, 2) CA group, 3) CA + NSC23766 group (NSC), and 4) CA + saline group. NSC23766 (50 μg, intracerebroventricular injection) or isotonic saline was administered 15 minutes before CA. Neurological function of rats after reperfusion was scored using the neurological deficit score evaluation method. Survival rates, neuronal counts, Rac1 activation, mitochondrial ROS formation and expression of thioredoxin2 (Trx2) and peroxiredoxin3 (Prx3) in the hippocampal CA1 region were assessed after reperfusion. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion.

Results: NSC23766, the specific inhibitor of Rac1 GTPase, significantly attenuated neuronal damage and reduced the spatial learning and memory deficits associated with global cerebral ischemia induced by CA (P<0.05). Furthermore, NSC23766 exerted its neuroprotective function by decreasing the ROS generation (P<0.05). However, there was no significant difference of Trx2 and Prx3 protein expression in hippocampal CA1 region between the CA group and NSC group after 1 day reperfusion (P<0.05). 

Conclusions: Our findings suggested that NSC23766 not only ameliorated post-ischemic neuronal cell death, but also improved learning and memory deficits in a cerebral ischemia animal model through down-regulating ROS generation.

 

 

Citation: Juan Liao, Chang Xu, Chang Liu, Na Wang, Guo-Qing Huang, Chang-Sheng Huang, et al. NSC23766, a specific inhibitor of Rac1 GTPase, attenuated delayed neuronal cell death and cognitive deficit in rats with cardiac arrest. J Anesth Perioper Med 2015; 2: 136-45. doi: 10.24015/JAPM.2015.0019

This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

 

Copyright © 2014-2018 | Evidence Based Communications (EBC)   All Rights Reserved.
Privacy Policy | Terms of Use | NIH Public Access Policy
ISSN: 2306-773X (Print) and 2520-3002 (Online)Submit a Manuscript | EBC and EBC Journals

The content on this site is intended for health professionals.
Loading