Protective effects of 8-MOP on blood-brain barrier via the Nrf-2/HO-1 pathway in mice model of cerebral infarction.

OBJECTIVE: To explore the effect of 8-MOP on the blood-brain barrier in mice model of cerebral infarction and the underlying mechanism.

MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) model was established to induce permanent cerebral infarction. The neurological function was observed and scored by the modified longa score method after model establishment. Besides, the water content of brain tissue was measured by the standard dry weight method. Evans blue exudation rate was used to evaluate the effect of 8-MOP on the permeability of the blood-brain barrier. Western-blot and quantitative polymerase chain reaction (qPCR) were used to detect the expression of MMP-9, claudin-5, vascular endothelial growth factor (VEGF), as well as the NFE2-related factor 2 (Nrf-2)/hemeoxygenase 1 (HO-1) pathway.

RESULTS: 8-MOP could reduce the neurological deficit scores in a dose-dependent manner, thereby reducing cerebral edema. After 8-MOP treatment, the expression of MMP-9 decreased in ischemic brain tissue, whereas the expression of claudin-5, VEGF, and GFAP increased, suggesting that the blood-brain barrier ultrastructure was improved. In addition, the expression of Nrf-2 and HO-1 decreased after the model establishment of cerebral infarction. However, the expression of Nrf-2 and HO-1 increased in ischemic brain tissue after 8-MOP treatment.

CONCLUSIONS: 8-MOP may protect the blood-brain barrier via the Nrf-2/HO-1 pathway.