Cerebral tissue pO2 response to treadmill exercise in awake mice

Abstract

We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO 2 response to forced treadmill exercise in awake mice. to our knowledge, this is the first study performing both direct measure of brain tissue pO 2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO 2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5-15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease.

Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO2, and pO2

“…Based on studies in awake rats under hypoxic breathing conditions (Dunn et al, 2011;Ortiz-Prado et al, 2010), there is a similar percentage drop between arterial and tissue pO 2 that lasts for exposures of 1-2 days. The theoretical prediction of tissue pO 2 being maintained during activation within 10% boundaries during activation is in agreement with recent measurements in activated brain regions in awake mice (Moeini et al, 2019(Moeini et al, , 2020Zhang et al, 2019), and previous fitting of experimental CBF versus CMRO 2 data (Buxton, 2010;Buxton et al, 2014;Herculano-Houzel & Rothman, 2022;Ji et al, 2021).…”

“…Another limitation of this study is that the calculations of average tissue and , do not provide information on their microscopic blood and tissue distribution within a neurovascular unit. Based upon recent studies using high resolution optical imaging, regional levels within a neurovascular unit vary between approximately 2.0–0.5 times the mean value (Gould et al, 2017; Li et al, 2019; Lyons et al, 2016; Mächler et al, 2022; Moeini et al, 2018, 2019, 2020), The lower end of this range may explain the sensitivity of brain function to decreases in being greater than anticipated from average values. Due to its 20‐fold higher diffusivity, the range of is anticipated to be similar to the difference in arteriole and venule values (see Equation 34).…”

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation

“…could be in part due to an increase in Hct level due to exercise. (Moeini et al, 2020) We observed a moderate but statistically insignificant increase in Hct in the exercise group compared with sedentary mice (Figure 4c). No difference in the capillary RBC line-density between two groups was found (Figure 3 -Figure supplement 2).…”

Behavioral and Neural Activity-Dependent Recanalization of Plugged Capillaries in the Brain of Adult and Aged Mice

“…The idea that components of enrichment, such as exercise, can augment cerebral blood flow and therefore could affect capillary recanalization, is not new. Many rodent studies have shown that exercise can increase capillary blood flow, tissue oxygenation, and microvascular density in the cerebral cortex (Swain et al, 2003;Murugesan et al, 2012;Huang et al, 2013;Moeini et al, 2020). Indirect evidence that exercise might improve recanalization comes from the fact that it could prevent the inevitable consequence of recanalization failure (Reeson et al, 2018), namely, vessel pruning and the appearance of string vessels (Leardini-Tristão et al, 2020;Trigiani et al, 2020).…”