Effects of exercise on cerebrovascular and brain function in the setting of heart failure

Background: Heart failure (HF) is associated with reduced cerebral perfusion, which may lead to impaired neurogenesis. Exercise training (EX) has been proven to increase cerebral perfusion and neurogenesis. Using a rodent model of HF, this study tested two hypotheses: EX recovers (1) reduced cerebral perfusion and (2) reduced neurogenesis in the subventricular zone of the lateral ventricle in the setting of HF. This region was selected as newborn neurons generated there may be involved in neuroplasticity and repair. Methods: Male Sprague Dawley rats underwent either a sham ( n =13) or left anterior descending coronary artery ligation (model of HF; n=25 ). HF rats were subdivided into sedentary (HF-SED; n =11) or EX (HF-EX ; n =14). Exercise consisted of progressive treadmill running (3-days/week). Internal carotid artery blood flow (BF; perivascular flow probe) and cardiac output (CO; echocardiography) were measured at 6- or 12-weeks post-ligation. Injections of 5-ethynyl-2’-deoxyuridine (EdU; 50ug/kg/day for 3-days) were performed two weeks prior to euthanasia at 6- or 12-weeks. EdU is a thymine analogue used to assess cell proliferation. Following euthanasia, rat brains were harvested, stained for EdU, and counterstained for neuronal N (NeuN) to quantify neurogenesis. Results: Internal carotid artery BF was not lower in the HF-SED vs. the Sham-SED groups at either time point (6- and 12-weeks pooled: HF-SED: 8.6±3.8 ml/min and 12.3±4.8 %CO, Sham-SED: 11.1±3.1 ml/min and 14.4±4.5 %CO, HF-EX: 11.2±6.1 ml/min and 15.9±10.3 %CO, P≥0.44). However, absolute internal carotid artery BF and BF scaled as a percentage of total CO were greater in the HF-EX group compared to both the Sham-SED and HF-SED groups at the 12-week timepoint (12-weeks: HF-SED: 9.7±5.0 ml/min and 12.3±6.2 %CO, Sham-SED: 12.0±3.9 ml/min and 15.0±5.0 %CO, HF-EX: 17.8±1.8 ml/min and 23.5±9.4 %CO, P≤0.03). In the anterior lateral ventricle, the total number of EdU + cells were similar across groups (Sham-SED: 369±129 mm 2 , HF-SED: 309±119 mm 2 , HF-EX: 363±166 mm 2 , P≥0.24). However, at 12 weeks the number of EdU + cells co-labeled with NeuN + was lower in the HF-SED vs. Sham-SED group (Sham-SED: 157±102 mm 2 , HF-SED: 41±26 mm 2 , P=0.02), but approached significance in the HF-EX vs. Sham-SED group (HF-EX: 76±60 mm 2 , P=0.07). Conclusions: The major novel finding of this work shows that HF alone results in deficits in neurogenesis in the subventricular zone of lateral ventricle, suggestive perhaps of reduced neuroplasticity. Further, we show EX provides modest protection against HF-induced deficits, highlighting its critical role in cardiac rehabilitation. Heart & Stroke Foundation, NSERC This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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