Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion.
OBJECTIVE
Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats.


METHODS
The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope.


RESULTS
Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01).


CONCLUSIONS
Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China.
Zhi-You
ZY
Cai
Yong
Y
Yan
Shan-Quan
SQ
Sun
Jun
J
Zhang
Liang-Guo
LG
Huang
Ning
N
Yan
Fang
F
Wu
Jie-Ying
JY
Li
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002340:Carotid Artery Diseases / Q000150:complications; D017536:Carotid Artery, Common; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D018782:Maze Learning / Q000187:drug effects; D008911:Minocycline / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D008911:Minocycline