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.

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Background: Previous studies on the novel Coronavirus (COVID-19) have found strong correlations between online searches and the epidemiology of the disease. Aim: Our aim was to determine if online searches for COVID-19 related to international media announcements or national epidemiology. Methods: Searches for "coronavirus" were made on Google Trends from December 31, 2019 to April 13, 2020 for 40 European countries. The online COVID-19 searches for all countries were correlated with each other. COVID-10 epidemiology (i.e. incidence and mortality) was correlated with the national online searches. Major announcements by the World Health Organization (WHO) were taken into consideration with peaks in online searches. Correlations were made using Spearman's rank correlation coefficient. Results: Overall, the online searches for COVID-19 were not correlated with the actual incidence and mortality of COVID-19. The mean Spearman correlation for incidence was 0.20 (range À0.66 to 0.76) and for mortality was 0.35 (range À0.75 to 0.85). Online searches in Europe were all strongly synchronized with each other; a mean Spearman correlation of 0.93 (range 0.62 to 0.99). Conclusions: Online searches for COVID-19 in Europe are not correlated with epidemiology but strongly correlated with international WHO announcements. Our study challenges previous Google Trends studies and emphasizes the role of the WHO in raising awareness of a new disease.

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