Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats.
OBJECTIVE
To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats.


METHODS
Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1alpha levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis.


RESULTS
Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1alpha), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage.


CONCLUSIONS
The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.
Liao
Yun
Y
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Wang
Rui
R
Tang
Xi-can
XC
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000523:psychology*; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D002504:Meclofenoxate / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D002504:Meclofenoxate