Mechanisms of stroke protection by physical activity

Abstract

Regular physical activity is associated with a decrease of cerebrovascular and cardiovascular events, which may relate to enhanced endothelium-dependent vasodilation. Here, we provide evidence that physical activity protects against ischemic stroke via mechanisms related to the upregulation of endothelial nitric oxide synthase (eNOS) in the vasculature. Voluntary training on running wheels or exercise on a treadmill apparatus for 3 weeks, respectively, reduced cerebral infarct size and functional deficits, improved endothelium-dependent vasorelaxation, and augmented cerebral blood flow in wild-type mice. The neuroprotective effects of physical training were completely absent in eNOS-deficient mice, indicating that the enhanced eNOS activity by physical training was the predominant mechanism by which this modality protects against cerebral injury. Our results suggest that physical activity not only decreases stroke risk, but also provides a prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia.

Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training

“…An impaired cerebrovascular reactivity has been identified as a risk factor for stroke [4][5][6]. In addition, an elevated cardiorespiratory fitness has been associated with a reduced risk of stroke (Endres et al 2003;Gertz et al 2006;Lee and Paffenbarger 1998;Hooker et al 2008). This fitness-induced elevation in cerebrovascular reactivity may provide an important physiological link in the relationship between fitness and cerebrovascular disease.…”

“…Furthermore, a link between the systemic endothelial function and cerebrovascular reactivity has been established (Ainslie et al 2007;Lavi et al 2006), indicating that any improvements in systemic vascular function might also be reflected in the cerebral circulation (as now demonstrated in this study). In addition, the reduced stroke risk and improved long-term outcome as a result of physical activity have been postulated to be due to upregulation of endothelial NO synthase (Endres et al 2003;Gertz et al 2006). Additional mechanisms potentially contributing to this increased cerebrovascular reactivity include brain-derived neurotrophic factor (Seifert et al 2010) and insulin-like growth factor-1 (Llorens-Martin et al 2010).…”

“…Whether similar improvements can be observed in healthy young and older individuals following a lesser amount of exercise training is unknown. This fitness-induced reduction in the risk of stroke is due to upregulation of endothelial NO synthase (Endres et al 2003;Gertz et al 2006;Lee and Paffenbarger 1998). Furthermore, it is known that hypercapnia-induced cerebrovascular vasodilatation is, at least in part, NO dependent (Peebles et al 2007).…”

Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle

“…80 Although endothelial nitric oxide synthase (eNOS) has a prototypic role in regulating vascular function, neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) have recently emerged as important mediators of vascular reactivity and tissue perfusion in experimental models. [81][82][83] For example, eNOS expression is increased during exercise, 84 and its regulation may help to maintain microvascular health. 85 Recently, HIF-derived increases in skin iNOS expression have been shown to divert blood flow toward the skin, causing a reduction in kidney perfusion and accentuating renal hypoxic responses.…”

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…Repeated transient shear stress induces NOS3 (eNOS gene) transcription and leads thus to chronically higher NO production in response to stimuli. This is one explanation for the beneficial effect of physical exercise [26,27]. Shear stress is also the key concept for testing endothelial dysfunction in vivo.…”