Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia

Abstract

Physical exercise is known to be a beneficial factor by increasing the cellular stress tolerance. In ischemic stroke, physical exercise is suggested to both limit the brain injury and facilitate behavioral recovery. In this study we investigated the effect of physical exercise on brain damage following global cerebral ischemia in mice. We aimed to study the effects of 4.5 weeks of forced treadmill running prior to ischemia on neuronal damage, neuroinflammation and its effect on general stress by measuring corticosterone in feces. We subjected C57bl/6 mice (n = 63) to either treadmill running or a sedentary program prior to induction of global ischemia. Anxious, depressive, and cognitive behaviors were analyzed. Stress levels were analyzed using a corticosterone ELISA. Inflammatory and neurological outcomes were analyzed using immunohistochemistry, multiplex electrochemoluminescence ELISA and Western blot. To our surprise, we found that forced treadmill running induced a stress response, with increased anxiety in the Open Field test and increased levels of corticosterone. In accordance, mice subjected to forced exercise prior to ischemia developed larger neuronal damage in the hippocampus and showed higher cytokine levels in the brain and blood compared to non-exercised mice. The extent of neuronal damage correlated with increased corticosterone levels. To compare forced treadmill with voluntary wheel running, we used a different set of mice that exercised freely on running wheels. These mice did not show any anxiety or increased corticosterone levels. Altogether, our results indicate that exercise pre-conditioning may not be beneficial if the animals are forced to run as it can induce a detrimental stress response.

Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum

“…The extent of the ischaemic brain injuries is assessed in separate studies (pMCAO and CCH (Deierborg, unpublished); GCIR (Svensson et al . )). No lesions or abnormalities were noted upon inspection of the visceral organs at necropsy.…”

“…; Svensson et al . ). The prevailing view is that central neuronal losses in all three stroke models used involve activation of a common gal‐3/TLR4 pathway.…”

“…; Svensson et al . ). Mice (sham n = 5, GCIR n = 5) had a cut made parallel to the trachea, and the common carotid arteries were exposed bilaterally.…”

“…; Svensson et al . ; Liu et al . ), and no impact on enteric neurons is to be expected until after the brain injury.…”

Caloric restriction suppresses exercise-induced hippocampal BDNF expression in young male rats

“…From these observations, we assume that the increase in 4-HNE levels of CR and ExCR might be attenuated by elevating CORT. Furthermore, acute mild (15 m/min) treadmill exercise did not affect CORT induction 36) , whereas chronic exercise at the same load accumulated serum CORT levels 38) . Accordingly, treadmill exercise training could enhance the CORT production induced by 40% caloric restriction, which might lead to greater suppression of the increase in hippocampal 4-HNE levels in ExCR rats.…”