Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

被引：59

作者：

Cai Z.-Y. ^{[1
]}

Yan Y. ^{[1
]}

Sun S.-Q. ^{[2
]}

Zhang J. ^{[3
]}

Huang L.-G. ^{[3
]}

Yan N. ^{[1
]}

Wu F. ^{[1
]}

Li J.-Y. ^{[1
]}

机构：

[1] Department of Neurology, Chongqing Medical University, Chongqing Key Laboratory of Neurology

[2] Department of Anatomy, Chongqing Medical University

[3] Department of Neurology, Zunyi Medical College

来源：

Neuroscience Bulletin | 2008年 / 24卷 / 5期

关键词：

Minocycline; Nitric oxide synthase; Vascular dementia;

D O I：

10.1007/s12264-008-0324-y

中图分类号：

学科分类号：

摘要：

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). Conclusion: 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. © 2008 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag GmbH.

引用

页码：305 / 313

页数：8

共 25 条

[11]

Chi O.Z., Hunter C., Liu X., Weiss H.R., Effects of VEGF and nitric oxide synthase inhibition on blood-brain barrier disruption in the ischemic and non-ischemic cerebral cortex, Neurol Res, 27, pp. 864-868, (2005)

[12]

Weng Y.C., Kriz J., Differential neuroprotective effects of a minocycline-based drug cocktail in transient and permanent focal cerebral ischemia, Exp Neurol, 204, pp. 433-442, (2007)

[13]

Rosenberg G.A., Estrada E.Y., Mobashery S., Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide-induced blood-brain barrier opening in rodents: Differences in response based on strains and solvents, Brain Res, 1133, pp. 186-192, (2007)

[14]

Xu L., Fagan S.C., Waller J.L., Edwards D., Borlongan C.V., Zheng J., Et al., Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats, BMC Neurol, 4, (2004)

[15]

Pattison L.R., Kotter M.R., Fraga D., Bonelli R.M., Apoptotic cascades as possible targets for inhibiting cell death in Huntington's disease, J Neurol, 253, pp. 1137-1142, (2006)

[16]

Choi Y., Kim H.S., Shin K.Y., Kim E.M., Kim M., Kim H.S., Et al., Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models, Neuropsychopharmacology, 32, pp. 2393-2404, (2007)

[17]

Zhu S., Stavrovskaya I.G., Drozda M., Kim B.Y., Ona V., Li M., Et al., Minocycline inhibits cytochrome C release and delays progression of amyotrophic lateral sclerosis in mice, Nature, 417, pp. 74-78, (2002)

[18]

Wang X., Zhu S., Drozda M., Zhang W., Stavrovskaya I.G., Cattaneo E., Et al., Minocycline inhibits caspase-independent and-dependent mitochondrial cell death pathways in models of Huntington's disease, Proc Natl Acad Sci U S a, 100, pp. 10483-10487, (2003)

[19]

Wu D.C., Jackson-Lewis V., Vila M., Tieu K., Teismann P., Vadseth C., Et al., Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease, J Neurosci, 22, pp. 1763-1771, (2002)

[20]

Chu L.S., Fang S.H., Zhou Y., Yu G.L., Wang M.L., Zhang W.P., Et al., Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats, Acta Pharmacol Sin, 28, pp. 763-772, (2007)

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