The alterations of oligodendrocyte, myelin in corpus callosum, and cognitive dysfunction following chronic cerebral ischemia in rats

Although the white matter lesions, so called leuko-araiosis, often seen in elderly people have been gaining attention due to their association with cognitive dysfunction (CD) and high risk of incident stroke, the pathological significance of these lesions still remains controversial. Therefore, in the present study, we investigated the alterations in oligodendrocytes (OLG), including oligodendrocytes progenitor cells (OPCs), myelin, and CD following chronic cerebral ischemia in rats. SD rats were subjected to bilateral common carotid artery occlusion. Immunohistochemical staining was performed at 2, 4, 6, 8, and 12 weeks after the induction of ischemia with anti-NG2 (OPCs), anti-GST-π (OLG), and anti-MBP antibodies in paramedian corpus callosum (CC). CD was assessed by the Morris water maze test. There was a significant decrease in the number of GST-π positive cells at 2 weeks after the start of ischemia compared with that seen in the sham group. There was a significant increase of the number of NG2 positive cells at 4 weeks in the ischemia group compared with the sham group. In the ischemic group, the amount of MBP was observed to have decreased significantly at each time point compared with the sham group. CD was observed in the ischemic group than that in the sham group at all time points. Our results indicate that remyelination is strongly correlated with the recovery of cognitive dysfunction following chronic cerebral ischemia.

► The peak of proliferation of the oligodendrocyte progenitor cell is at 4 weeks following chronic cerebral ischemia.
► The oligodendrocyte restored up to the level of sham groups at 4 weeks following chronic cerebral ischemia.
► The myelin decrease after 2 weeks of chronic cerebral ischemia and persisted until 12 weeks.
► The cognitive dysfunction was observed after 2 weeks of chronic cerebral ischemia and persisted until 12 weeks.
► The remyelination is correlated with the recovery of the cognitive dysfunction following chronic cerebral ischemia.