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
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
收藏
页码:305 / 313
页数:8
相关论文
共 25 条
[1]  
Morimoto N., Shimazawa M., Yamashima T., Nagai H., Hara H., Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage, Brain Res, 1044, pp. 8-15, (2005)
[2]  
Lin S., Zhang Y., Dodel R., Farlow M.R., Paul S.M., Du Y., Minocycline blocks nitric oxide-induced neurotoxicity by inhibition p38 MAP kinase in rat cerebellar granule neurons, Neurosci Lett, 315, pp. 61-64, (2001)
[3]  
Yrjanheikki J., Tikka T., Keinanen R., Goldsteins G., Chan P.H., Koistinaho J., A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window, Proc Natl Acad Sci U S a, 96, pp. 13496-13500, (1999)
[4]  
Yu C.Y., Cai Z.Y., Effect of minocycline on expression of MMP-2 and MMP-9 in rats with focal cerebral ischemic-reperfusion, J Guizhou Med China, 30, pp. 983-985, (2006)
[5]  
Stirling D.P., Khodarahmi K., Liu J., McPhail L.T., McBride C.B., Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury, J Neurosci, 24, pp. 2182-2190, (2004)
[6]  
Hewlett K.A., Corbett D., Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia, Neuroscience, 141, pp. 27-33, (2006)
[7]  
Vannucchi M.G., Bizzoco E., Corsani L., Gianfriddo M., Pedata F., Faussone-Pellegrini M.S., Relationships between neurons expressing neuronal nitric oxide synthase, degree of microglia activation and animal survival. a study in the rat cortex after transient ischemia, Brain Res, 1132, pp. 218-227, (2007)
[8]  
Pluta R.M., Rak R., Wink D.A., Woodward J.J., Khaldi A., Oldfield E.H., Et al., Effects of nitric oxide on reactive oxygen species production and infarction size after brain reperfusion injury, Neurosurgery, 48, pp. 884-893, (2001)
[9]  
Mishra O.P., Mishra R., Ashraf Q.M., Delivoria-Papadopoulos M., Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets, Neuroscience, 140, pp. 857-863, (2006)
[10]  
Han F., Shirasaki Y., Fukunaga K., Microsphere embolism-induced endothelial nitric oxide synthase expression mediates disruption of the blood-brain barrier in rat brain, J Neurochem, 99, pp. 97-106, (2006)