Involvement of Arterial Baroreflex in the Protective Effect of Dietary Restriction Against Stroke

Abstract

Dietary restriction (DR) protects against neuronal dysfunction and degeneration, and reduces the risk of ischemic stroke. This study examined the role of silent information regulator T1 (SIRT1) and arterial baroreflex in the beneficial effects of DR against stroke, using two distinct stroke models: stroke-prone spontaneously hypertensive rats (SP-SHRs) and Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Sirt1 knockout (KO) mice were used to examine the involvement of sirt1. Sinoaortic denervation was used to inactivate arterial baroreflex. Dietary restriction was defined as 40% reduction of dietary intake. Briefly, DR prolonged the life span of SP-SHRs and reduced the infarct size induced by MCAO. Dietary restriction also improved the function arterial baroreflex, decreased the release of proinflammatory cytokines, and reduced end-organ damage. The beneficial effect of DR on stroke was markedly attenuated by blunting arterial baroreflex. Lastly, the infarct area in sirt1 KO mice was significantly larger than in the wild-type mice. However, the beneficial effect of DR against ischemic injury was still apparent in sirt1 KO mice. Accordingly, arterial baroreflex, but not sirt1, is important in the protective effect of DR against stroke.

Mitochondrial function in hypoxic ischemic injury and influence of aging

“…A direct role for SIRT1 in ischemic stroke is suggested by the fact that SIRT1 knockout mice have increased infarct size when subjected to middle cerebral artery occlusion (Hernandez-Jimenez et al , 2013; Liu et al , 2013a). SIRT1 activators decrease infarct size (Gao et al , 2006; Huang et al , 2001; Li et al , 2012; Lu et al , 2006; Tsai et al , 2007; Yousuf et al , 2009) while SIRT1 inhibitors had an adverse effect (Hernandez-Jimenez et al , 2013).…”

Sirtuin regulation in aging and injury

“…Additionally the expression of SIRT1, PGC-1α and phosphorylation of cyclic AMP-response-element-binding protein were augmented with a reduction in anti-apoptotic Bcl2 transcription [281]. A direct role for SIRT1 in stroke is evident from studies that show greater infarct size in SIRT1 knockout mice that underwent middle cerebral artery occlusion compared to wild type mice [282, 283]. The infarct volume was also affected by pharmacologic modulation of SIRT1; SIRT1 activator A3 decreased infarct volume whereas sirtinol increased the infarct volume.…”

Dietary restriction in cerebral bioenergetics and redox state

“…However, the role of SIRT1 in the brain remains unclear since, although SIRT1 knockout animals show larger infarct sizes than wild type mice, these animals can still respond to a 40% FR diet by decreasing both the extent of the infarct volume and the neurological deficit [62]. In addition, NAD + consumption due to SIRT1 activation could be detrimental to stroke outcome [83].…”