Exercise pre-conditioning ameliorates blood–brain barrier dysfunction in stroke by enhancing basal lamina

Abstract

Objective: We investigated whether exercise pre-conditioning ameliorates stroke-induced blood–brain barrier (BBB) dysfunction by strengthening basal lamina.

Methods: Adult male Sprague–Dawley rats were subjected to a 30 minute exercise program on a treadmill each day for 3 weeks. Stroke was induced by a 2 hour middle cerebral artery (MCA) occlusion using an intraluminal filament in the exercised and non-exercised groups. BBB dysfunction was then determined by brain edema. Expression of collagen IV, the major component of basal lamina essential for maintenance of the endothelial permeability barrier, was quantitatively detected by Western blot and immunocytochemistry. Ex vivo techniques were used to compare collagen IV-labeled vessels in response to ischemic insult.

Results: Brain edema was significantly (p<0.05) reduced after stroke in the exercised group. Western blot analysis indicated that exercise pre-conditioning enhanced collagen IV expression and reduced the loss after stroke. Immunocytochemistry demonstrated that collagen IV-positive vessels were significantly (p<0.01) increased in exercised rats. In ex vivo study, after exercised brain was incubated with ischemic brain tissue, a significantly (p<0.01) higher expression of collagen IV in cortex and striatum was observed compared to non-exercised brain following the same treatment. The ex vivo study also revealed that matrix metalloproteinase (MMP)-9 plays a key role in exercise-strengthened collagen IV expression against ischemia/reperfusion injury.

Discussion: Our results indicate that exercise pre-conditioning improved BBB function and enhanced basal lamina, which involved MMP-9.

Keywords:

• ISCHEMIA AND REPERFUSION INJURY
• COLLAGEN IV
• EX VIVO
• MMP-9
• ECM