Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion

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 Klüver-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.

Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion

“…Moreover, chronic cerebral hypoperfusion leads neuronal damage not only in the hippocampus but also in the cortex (Shibata et al, 2004;Cho et al, 2006;Ueno et al, 2009). In present research, we observed the protective effects of LIG on both parietal cortex and hippocampus of 2VO rats.…”

Cytokine regulation of MMP-9 in peripheral glia: Implications for pathological processes and pain in injured nerve

“…It is known to control the breakdown of MBP (Chandler et al, 1995), a late component of myelin formation that is produced by Schwann cells in injured peripheral nerve (Gupta et al, 1988;LeBlanc and Poduslo, 1990). While MMP-9-dependent degradation of MBP has been shown in models of multiple sclerosis (Gijbels et al, 1993;Proost et al, 1993) and cerebral ischemia (Asahi et al, 2001;Cho et al, 2006), this is the first demonstration of this relationship in the PNS. Other MMPs, such as MMP-12 (Larsen et al, 2006) andMMP-3 (D'Souza andMoscarello, 2006), regulate MBP processing in the CNS and may play a role in peripheral nerve.…”

Environmental enrichment prevents behavioral deficits and oxidative stress caused by chronic cerebral hypoperfusion in the rat

“…Several authors have shown that the long-lasting learning deficits observed in these rats are at least partially attributable to damage to the white matter (Zhang et al, 2011). Cho et al (2006) identified that the main areas affected are corpus callosum, optic tract, and internal capsule in rats with chronic cerebral hypoperfusion. Experimental evidence demonstrated the initiating role of chronic cerebral hypoperfusion in neural damage to the white matter (WM) areas and the visual system.…”