Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion.
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.
Cho
Kyung-Ok
KO
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
La
Hyen O
HO
Cho
Young-Jin
YJ
Sung
Ki-Wug
KW
Kim
Seong Y
SY
D000704:Analysis of Variance; D000818:Animals; D001925:Brain Damage, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003337:Corpus Callosum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015140:Dementia, Vascular / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008911:Minocycline / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014795:Visual Pathways / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D020778:Matrix Metalloproteinase 2; D008911:Minocycline