Alteration in P-glycoprotein at the blood–brain barrier in the early period of MCAO in rats

Abstract

Abstract Objectives The aim of this work was to investigate the alteration in P-glycoprotein (P-gp) at the blood–brain barrier (BBB) after middle cerebral artery occlusion (MCAO) in rats. Methods Permanent MCAO was verified via 2,3,5-triphenyltetrazolium staining and hematoxylin-eosin staining. The expression of P-gp, matrix metalloproteinase-2 (MMP-2), MMP-9, claudin-5, tumour necrosis factor-α (TNF-α) and nitric oxide synthase (NOS) at the BBB was evaluated using western blot or immunostaining analysis. The content of fluorescein sodium (NaF), rhodamine-123 and nimodipine in ischaemic brain tissues was determined using high-performance liquid chromatography. Key findings Elevated expression of P-gp at the BBB and decreased concentration of P-gp substrates in the ischaemic brain tissues were observed within 4 h after MCAO. However, at 6 h after MCAO, the concentration of P-gp substrates in the ischaemic hemisphere began to rise even though the expression of P-gp was still increased. Moreover, the expression of claudin-5 was decreased; contrarily, the expression of MMP-2, MMP-9, TNF-α as well as NOS gradually increased within 6 h after MCAO. Conclusions P-gp plays a crucial role in limiting the entrance of agents into the brain after MCAO and the specific regulation of P-gp expression/activity may provide an important approach for the improvement of pharmacotherapy in ischaemic stroke.