Research reportEarly rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX)

- Exercise was imposed on rats 6 h, 24 h, or 3d after reperfusion from ischemic stroke.
- Exercise 6 h after reperfusion increased apoptotic cell death, expression of hyperglycolytic markers, and NOX activation.
- Post-stroke exercise may be detrimental if initiated too soon after reperfusion.
- 24 h may be a delineating time, before which, post-stroke exercise may be detrimental, and after which, it may be beneficial.

IntroductionAlthough physical exercise has emerged as a potential therapeutic modality for functional deficits following ischemic stroke, the extent of this effect appears to be contingent upon the time of exercise initiation. In the present study, we assessed how exercise timing affected brain damage through hyperglycolysis-associated NADPH oxidase (NOX) activation.MethodsUsing an intraluminal filament, adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and assigned to one non-exercise and three exercise groups. Exercise on Rota-rod was initiated for 30 min at 6 h (considered very early), at 24 h (early), and at day 3 (relatively late) after reperfusion. Lactate production was measured 30 min after exercise completion, and NOX activity and protein expression of NOX subunits (p47phox, gp91phox, p22phox and p67phox) and glucose transporter 1 and 3 (Glut-1 and -3) were measured at 3 and 24 h after exercise. Apoptotic cell death was determined at 24 h after exercise.ResultsLactate production and Glut-1 and Glut-3 expression were increased after very early exercise (6 h), but not after late exercise (3 days), suggesting hyperglycolysis. NOX activity was increased with the initiation of exercise at 6 h (P<0.05), but not 24 h or 3 days, following stroke. Early (6 and 24 h), but not late (3 days), post-stroke exercise was associated with increased (P<0.05) expression of the NOX protein subunit p47phox, gp91phoxand p67phox. This may have led to the enhanced apoptosis observed after early exercise in ischemic rats.ConclusionHyperglycolysis and NOX activation was associated with an elevation in apoptotic cell death after very early exercise, and the detrimental effect of exercise on stroke recovery began to decrease when exercise was initiated 24 h after reperfusion.