Preischemic Treadmill Exercise Ameliorates Memory Impairment and Microvasculature Damage in Rat Model of Chronic Cerebral Hypoperfusion

Abstract

Purpose: Silent information regulator 1 (SIRT1) in the brain is essential for maintaining cellular homeostasis and plays a neuroprotective role in cerebral ischemia and neurodegenerative disorders. The effect of preischemic treadmill exercise on chronic cerebral hypoperfusion (CCH)-induced spatial learning memory impairment, microvascular injury, and blood-brain barrier (BBB) disruption in relation with SIRT1 expression was evaluated.Methods: Prior to bilateral common carotid artery occlusion (BCCAO) surgery, the rats in the exercise groups performed low-intensity treadmill running for 30 minutes once daily during 8 weeks. BCCAO surgery was performed on male Wistar rats at 12 weeks of age. Spatial learning memory was measured using the Morris water maze test. Neuronal nuclear antigen, SIRT1, and rat endothelial cells antigen 1 were determined by immunohistochemistry and platelet-derived growth factor receptor beta was determined by immunofluorescence.Results: Preischemic treadmill exercise ameliorated spatial learning memory impairment and enhanced SIRT1 expression in the BCCAO rats. Preischemic treadmill exercise ameliorated BCCAO-induced damage to microvasculature and pericytes that make up the BBB. The effect of preischemic treadmill exercise was lost with sirtinol treatment.Conclusions: These results can apply treadmill exercise prior to cerebral ischemia as a rational preventive and therapeutic intervention strategy to improve cognitive dysfunction in CCH patients.

Intrinsic diving reflex enhances cognitive performance by alleviating microvascular dysfunction in vascular cognitive impairment

“…Importantly, microvascular damage, as opposed to macrovascular damage, correlates with gradual impairments in both short-term recognition and long-term spatial memories, leading to a maximal loss of 50% in memory capacity. Our findings are consistent with prior research demonstrating microvascular thinning and shortening [15], decreased perfused capillaries and microvascular density [11,49–52], and diminished vasodilatory response [14] at the later stage of 2VO. This study underscores the importance of microvascular dysfunction in VCI, elucidating the relationship between its gradual progression and the development of cognitive dysfunction.…”

“…From a mechanistic perspective, the effects of DR may be attributed to a combination of trigeminal nerve stimulation, apnea, and peripheral vasoconstriction (Fig 10). While physical activities such as running and swimming can induce an angiogenic response, these interventions necessitate a certain level of physical exertion to achieve efficacy [15,51,52,[66][67][68][69]. In human subjects, only high-intensity physical exercise, not moderate-intensity exercise, promotes an elevation in VEGF and nitric oxide, a key vasodilator [70].…”