Sigma-1 receptor activation alleviates blood-brain barrier dysfunction in vascular dementia mice.

Sigma-1 receptor activation alleviates blood-brain barrier dysfunction in vascular dementia mice.
Exp Neurol. 2018 Jul 10;:
Authors: Liu DY, Chi TY, Ji XF, Liu P, Qi XX, Zhu L, Wang ZQ, Lin-Li, Chen L, Zou LB
Abstract
Sigma-1 receptor (Sig-1R) activation has been shown to decrease infarct volume and enhance neuronal survival after brain ischemia-reperfusion (IR) in rodent models. The present study aims to investigate first the effect of Sig-1R activation on blood-brain barrier (BBB) disruption during experimental stroke. Male C57BL/6 mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 15 min, and the worst BBB leakage was observed on the 7th day after brain IR. To confirm the BBB protective role of Sig-1R, mice were divided into five groups (sham group, BCCAO group, PRE084 group, BD1047 group, PRE084 and BD1047 group; 29-35 mice for each group), and treated with agonist PRE084 (1 mg/kg) and/or antagonist BD1047 (1 mg/kg) for 7 days intraperitoneally once a day after BCCAO. Interestingly, PRE084 administration significantly improved neurobehavioral performance as well as healing of neuron damage and white matter lesions. PRE084 also reduced the leakage of Evans blue and IgG and attenuated the disassembly of BBB structural proteins, while the neuroprotective and BBB protective functions of PRE084 were blocked by BD1047. Furthermore, in Sig-1R knockout (Sig-1R KO) mice, brain IR produced more serious IgG...

Source: Experimental Neurology - July 10, 2018 Category: Neurology Authors: Liu DY, Chi TY, Ji XF, Liu P, Qi XX, Zhu L, Wang ZQ, Lin-Li, Chen L, Zou LB Tags: Exp Neurol Source Type: research