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The biochemical and cellular events that lead to secondary neural damage after traumatic brain injury (TBI) contribute to long-term disabilities, including memory deficits. There is a need to search for single and/or combined treatments aimed at reducing these TBI-related dysfunctions. The effects of citicoline and of voluntary physical exercise in a running wheel (3 weeks), alone or in combination, on TBI-related short-term (3 h) and long-term (24 h) object recognition memory (ORM) deficits, and on neurogenesis and neuroprotection were examined using a rodent model of TBI (controlled cortical impact injury). Citicoline improved memory deficits at the two times tested, while physical exercise only in the long-term test. Physical exercise had a clear neuroprotective effect as indicated by reduced interhemispheric differences in hippocampal formation and lateral ventricle volumes and in density of mature neurons in the hilus of the dentate gyrus and the perirhinal cortex. Physical exercise also increased cell proliferation and neurogenesis in the granular cell layer of the dentate gyrus. Some degree of neuroprotection of citicoline was suggested by reduced interhemispheric differences in the volume of the hippocampal formation. Contrary to what was expected, the effects of citicoline and physical exercise did not sum up.Furthermore, a negative interference between both treatments was found in several behavioral and histological variables. The promising profiles of both treatments as therapeutic tools in TBI when applied singly, underscore the need to carry out further works looking for other combined treatment regimens that increase the benefit of each treatment alone.4

The present experiment investigated the effects of aging on emotional behavior, without concomitant influences from any previous behavioral manipulation apart from weighing the rats. Anxiety-related behaviors were measured in the elevated plus-maze (EPM). Performance in the open field (OF) was also assessed to control for any effect of aging on exploratory behavior that could account for changes in emotional behavior. Fifty-two naïve male Wistar rats of 3 (3MO), 17 (17MO), or 24 (24MO) months, were submitted to two sessions (5 min each) of EPM, followed by two sessions (2 min each) of OF, on 4 consecutive days. The main emotional indices (open arm entries, ratio of open arm entries to total entries, time spent in open arms, ratio of time in open arms to time in four arms, open arm ends, and head dips) measured in the EPM indicated a lower level of anxiety in aged (24MO) than in young (3MO) rats, whereas middle-aged (17MO) rats showed intermediate values between those of 3MO and 24MO rats; 3MO rats showed higher general motor activity (number of rearings in closed arms of EPM and in OF, and higher number of areas crossed in OF) than 17MO and 24MO rats. We conclude that aging is associated with a decrease in anxiety and in general motor activity.

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