Influence of exercise training on ischemic brain injury in type 1 diabetic rats

Abstract

While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50 mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we measured infarct volume in all groups of rats following right MCA occlusion for 2 h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy was performed over the parietal cortex, and we measured responses of pial arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)-dependent, and a NOS-independent agonist in all groups of rats. We found that sedentary diabetic rats had significantly larger total, cortical, and subcortical infarct volumes following ischemia-reperfusion than sedentary nondiabetic, nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS-independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened ischemic brain injury following middle cerebral artery occlusion and restored impaired eNOS- and nNOS-dependent vascular function. Since the incidence of ischemic stroke is increased during T1D, we suggest that our finding are significant in that modest ExT may be a viable preventative therapeutic approach to lessen ischemia-induced brain injury that may occur in T1D subjects.

Fig. 1.

Top: representative 2-mm-thick TTC-stained coronal sections of the brains from sedentary and exercise training (ExT) nondiabetic (Nondb) and diabetic (Db) rats subjected to 2-h middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Dark stain indicates viable tissue, and complete lack of stain defines the infarct region. Bottom: mean data depicting total infarct volume in sedentary and ExT Nondb and Db rats. Values are means ± SE. *P < 0.05 vs. sedentary and ExT Nondb rats. **P < 0.05 vs. sedentary Db rats.

Fig. 2.

Cortical and subcortical infarct volumes in sedentary and ExT Nondb and Db rats. Values are means ± SE. *P < 0.05 vs. sedentary and ExT Nondb rats. **P < 0.05 vs. sedentary Db rats.

Fig. 3.

Response of cerebral arterioles to ADP in sedentary and ExT Nondb and Db rats. Values are means ± SE. *P < 0.05 vs. sedentary and ExT Nondb rats. **P < 0.05 vs. sedentary Db rats.

Fig. 4.

Response of cerebral arterioles to N-methyl-d-aspartic acid (NMDA) in sedentary ExT Nondb and Db rats. Values are means ± SE. *P < 0.05 vs. sedentary and ExT Nondb rats. **P < 0.05 vs. sedentary Db rats.

Fig. 5.

Response of cerebral arterioles to nitroglycerin in sedentary and ExT Nondb and Db rats. Values are means ± SE.