Militarine alleviates white matter damage and cognitive impairment in rats with chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion is a model for white matter lesions (WMLs) and cognitive impairment. In this study, we used the model in testing the protective effect of (-)-(2R)-1-(4-β-D-glucopyranosyloxy) benzyl-4-4-(β-D-glucopyranosyloxy)benzyl-2-isobutyl malate (militarine) on the white matter damaged. The model was established by bilateral common carotid ligation. Militarine (10 and 20 mg·kg^-1·d^-1) or saline was intragastrically administered daily for 30 days following the operation. Militarine (20 mg·kg^-1·d^-1)-treated rats exhibited significantly shorter escape latency, latency of the first time crossing and more numbers of platform crossings in Morris water maze task. Luxol fast blue (LFB) staining and Western blot analysis indicated that militarine promoted rehabilitation of white matter and increased levels of myelin basic protein (MBP) in the rats. Immunohistochemical staining for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) revealed that militarine (20 mg·kg^-1·d^-1) markedly suppressed loss of CNPase-positive oligodendrocytes in the rat model. In conclusion, militarine can improve WMLs and cognitive impairment in the rat chronic hypoperfusion model.