Journal
NEUROPHARMACOLOGY
Volume 85, Issue -, Pages 508-516Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2014.06.008
Keywords
Cerebral ischemia; Reactive oxygen species (ROS); Apoptosis; Diabetes; P53
Categories
Funding
- National Natural Science Foundation of China [81201018]
Ask authors/readers for more resources
NSC23766, a specific inhibitor of Rac1, has recently been shown to protect against cerebral ischemic injury, although the effects of NSC23766 in a diabetic model have not been examined. Therefore, the aim of our study was to investigate if NSC23766 provided neuroprotection in streptozotocin-induced diabetic rats and to determine the potential mechanism through which NSC23766 works. Diabetic Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 90 min. NSC23766 (10 or 30 mg kg(-1)) or isotonic saline were administered intraperitoneally twice daily starting 24 h after cerebral ischemia, for three consecutive days. Cerebral infarct volume, neurological deficit scores, neuronal apoptosis, and the release of cytochrome c, as well as the generation of ROS and mitochondrial integrity, were evaluated 96 h after reperfusion. In addition, the mitochondrial translocation of p53 and the expression of p53-upregulated modulator of apoptosis (PUMA) in the mitochondria of the cerebral ischemic cortex were determined by western blotting. NSC23766 not only ameliorated post-ischemic neuronal apoptosis but also decreased cerebral ischemia-induced mitochondrial p53 translocation and the expression of PUMA in mitochondria in diabetic rats. Thus, our data indicate that NSC23766 has therapeutic potential against cerebral ischemic reperfusion injury and that NSC23766 significantly ameliorates neuronal apoptosis by suppressing mitochondrial p53 translocation in streptozotocin-induced diabetic rats. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available