Retigabine protects the blood-brain barrier by regulating tight junctions between cerebral vascular endothelial cells in cerebral ischemia-reperfusion rats.

Objective: To investigate the effect of retigabine on the blood-brain barrier permeability in rats with cerebral ischemia-reperfusion and its mechanism.
Materials and Methods: A total of 90 Sprague-Dawley (SD) rats were selected to prepare a rat model of focal cerebral ischemia-reperfusion. The blood flow changes were detected using a laser Doppler flow meter, the percentage of the cerebral infarction volume was measured by means of the triphenyl tetrazolium chloride (TTC) staining, the effect of retigabine on the permeability of the blood-brain barrier after cerebral ischemia-reperfusion was examined via Evans blue (EB) staining, and the state of tight junctions between endothelial cells was determined via the transmission electron microscopy (TEM) technique. Immunohistochemistry was used to detect the effects of retigabine on the distribution and expressions of tight junction-associated proteins in the cerebral ischemia-reperfusion blood-brain barrier. Western blotting was adopted to examine the changes in the expressions of related proteins in cerebral ischemia-reperfusion tissues.
Results: At 48 h and 96 h after cerebral ischemia-reperfusion, retigabine notably reduced the cerebral infarction volume of rats, and the tight junctions between microvascular endothelial cells in the ischemic area opened up, the permeability of the blood-brain barrier was remarkably increased, and the permeability of the blood-brain barrier was significantly reduced under the action of retigabine. The expressions of claudin-5, occludin, and ZO-1 in the blood-brain barrier of the ischemic brain tissue significantly declined, and retigabine notably increased the expressions of three proteins and their distributions along the microvessels. At 3 h, 24 h, 48 h, and 96 h after cerebral ischemia-reperfusion, the expressions of the MMP-2 protein and MMP-9 protein in the ischemic brain tissue were evidently increased, which were inhibited by retigabine. Moreover, the expressions of the PKCδ protein in the ischemic brain tissue were markedly increased, which were significantly inhibited by retigabine.
Conclusions: The regulatory roles of retigabine in the distribution and expressions of claudin-5, occludin, and ZO-1 may be associated with the inhibition of the expressions of the MMP-2, MMP-9, and PKCδ proteins.