Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion
Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion
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DOI：
10.1002/jnr.20727
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发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Kim, SY
中科院分区：
文献类型：
--
作者：
Cho, KO;La, HO;Kim, SY
白色病变被认为是慢性脑缺血的结果，并构成了皮质下血管性痴呆的核心病理。已知这种稀疏与小胶质细胞活化有关。我们研究了米诺环素，一种小胶质细胞抑制剂，是否能减轻慢性脑灌注不足引起的白色损害，该脑灌注不足被用作血管性痴呆的模型。对雄性Wistar大鼠进行双侧颈总动脉永久性闭塞（BCCAO）以诱导慢性脑灌注不足。BCCAO后每天注射米诺环素或生理盐水，持续2周。在胼胝体和视束中，使用Kluver-Barrera观察到白色物质损伤。与盐水处理的对照组相比，米诺环素处理组的染色显著减弱。在对照组大鼠中，主要碱性蛋白（MBP），作为小胶质细胞标记物的Ox-42和基质金属蛋白酶（MMP）-2的免疫反应性在胼胝体中增加。米诺环素显著降低了这些变化。免疫荧光组织化学双标法证实Ox-42和MMP-2共表达。我们的研究结果表明，米诺环素长期治疗可以保护至少一些缺血性白色物质损伤，其机制可能与抑制小胶质细胞活化有关。(C)2005 Wiley-Liss，Inc.
White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Kluver-Barrera. staining was significantly attenuated in the minocycline-treated group compared to saline-treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox-42 as a microglial marker, and matrix metalloproteinase (MMP)-2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co-expression of Ox-42 and MMP-2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation. (C) 2005 Wiley-Liss, Inc.