Abstract
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 KlรผverโBarrera staining was significantly attenuated in the minocyclineโtreated group compared to salineโtreated controls. In control rats, immunoreactivities of major basic protein (MBP), Oxโ42 as a microglial marker, and matrix metalloproteinase (MMP)โ2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Coโexpression of Oxโ42 and MMPโ2 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. ยฉ 2005 WileyโLiss, Inc.