Background: Exercise preconditioning (EP+) is a useful and important procedure for the prevention of stroke. We aimed to ascertain whether EP+ protects against ischemic brain injury by preserving heat shock protein (HSP) 72-containing neurons in ischemic brain tissues. Methods: Adult male Sprague-Dawley rats (n=240) were used to assess the contribution of HSP72-containing neurons to the neuroprotective effects of EP+ on ischemic brain injury caused by transient middle cerebral artery occlusion. Results: Significant (P<0.05) increases in the percentages of both old HSP72-containing neurons (NeuN+HSP72 double positive cells) (18 similar to 20% vs. 40 similar to 50%) and newly formed HSP72-containing neurons (BrdU+NeuN+HSP72 triple positive cells); (2 similar to 3% vs. 16 similar to 20%) after 3 weeks of exercise coincided with significant (P<0.05) reductions in brain ischemia volume (250 mm(3) vs. 100 mm(3)), brain edema (78% vs. 74% brain water content), blood-brain barrier disruption (1.5 mu g/g vs. 0.7 mu g/g tissue Evans Blue dye extravasation) and neurological motor deficits (neurological severity scores of 12 vs. 6 and maximal angles of 60 degrees vs. 20 degrees) in brain ischemia rats. Reductions in the percentages of both old (from 40 similar to 50% to 10 similar to 12%) and newly formed (from 18 similar to 20% to 5 similar to 7%) HSP72-containing neurons by gene silencing with an intracerebral injection of pSUPER small interfering RNA showed a significant (P<0.05) reversal in the neuroprotective outcomes. Our data provide an inverse correlation between the EP+-mediated increases in both old and newly formed HSP72-containing neurons and the extent of cerebral ischemic injury. Conclusions: The percentages of both old and newly formed HSP72-containing neurons are inversely correlated with the outcomes of ischemic brain injury. Additionally, preischemic treadmill exercise improves the outcomes of ischemic brain injury by preserving both the old and newly formed HSP72-containing neurons in rats.
關聯:
International Journal of Medical Sciences, v.16, n.5, pp.675-685
