Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent.
ABSTRACT We recently found that an exercise-induced increase in hippocampal brain-derived neurotrophic factor (BDNF) is dependent when exercise is initiated after traumatic brain injury (TBI). When voluntary exercise was delayed by 2 weeks after a mild fluid-percussion injury (FPI) in rats, an increase in BDNF and an improvement in behavioral outcome were observed. This suggests that following FPI there is a therapeutic window for the implementation of voluntary exercise. To determine if more severely injured animals require more time after TBI before voluntary exercise can increase neuroplasticity, adult male rats with a moderate lateral FPI or sham injury were housed with or without access to a running wheel from post-injury-day (PID) 0-6, 14-20 or 30-36. Rats with a mild injury only had access to the running wheel from PID 0-6 or 14-20. Rats were sacrificed at PID 7, 21, or 37. BDNF, synapsin I, and cyclic AMP response element binding protein (CREB) were analyzed within the ipsilateral hippocampus. Whereas BDNF levels significantly increased with exercise in the mild FPI rats that were exercised from PID 14 to 20, the moderate FPI rats only showed significant increases in BDNF when exercised from PID 30 to 36. In addition, moderate FPI rats that were allowed to exercise from PID 30 to 36 also exhibited significant increases in synapsin I and CREB. These results indicate that the time window for exercise-induced increases in BDNF, synapsin I, and CREB is dependent on injury severity.
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ABSTRACT: The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of “diversity” (total number of activities), “intensity” (hours per month), and “percentage intensity” (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65–5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20–39) to middle adulthood (40–60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.Proceedings of the National Academy of Sciences 03/2001; · 9.74 Impact Factor
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ABSTRACT: Voluntary exercise leads to an upregulation of brain-derived neurotrophic factor (BDNF) and associated proteins involved in synaptic function. Activity-induced enhancement of neuroplasticity may be considered for the treatment of traumatic brain injury (TBI). Given that during the first postinjury week the brain is undergoing dynamic restorative processes and energetic changes that may influence the outcome of exercise, we evaluated the effects of acute and delayed exercise following experimental TBI. Male Sprague-Dawley rats underwent either sham or lateral fluid-percussion injury (FPI) and were housed with or without access to a running wheel (RW) from postinjury days 0-6 (acute) or 14-20 (delayed). FPI alone resulted in significantly elevated levels of hippocampal phosphorylated synapsin I and phosphorylated cyclic AMP response element-binding-protein (CREB) at postinjury day 7, of which phosphorylated CREB remained elevated at postinjury day 21. Sham and delayed FPI-RW rats showed increased levels of BDNF, following exercise. Exercise also increased phosphorylated synapsin I and CREB in sham rats. In contrast to shams, the acutely exercised FPI rats failed to show activity-dependent BDNF upregulation and had significant decreases of phosphorylated synapsin I and total CREB. Additional rats were cognitively assessed (learning acquisition and memory) by utilizing the Morris water maze after acute or delayed RW exposure. Shams and delayed FPI-RW animals benefited from exercise, as indicated by a significant decrease in the number of trials to criterion (ability to locate the platform in 7 s or less for four consecutive trials), compared with the delayed FPI-sedentary rats. In contrast, cognitive performance in the acute FPI-RW rats was significantly impaired compared with all the other groups. These results suggest that voluntary exercise can endogenously upregulate BDNF and enhance recovery when it is delayed after TBI. However, when exercise is administered to soon after TBI, the molecular response to exercise is disrupted and recovery may be delayed.Neuroscience 02/2004; 125(1):129-39. · 3.12 Impact Factor
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ABSTRACT: Traumatic coma was produced in 45 monkeys by accelerating the head without impact in one of three directions. The duration of coma, degree of neurological impairment, and amount of diffuse axonal injury (DAI) in the brain were directly related to the amount of coronal head motion used. Coma of less than 15 minutes (concussion) occurred in 11 of 13 animals subjected to sagittal head motion, in 2 of 6 animals with oblique head motion, and in 2 of 26 animals with full lateral head motion. All 15 concussioned animals had good recovery, and none had DAI. Conversely, coma lasting more than 6 hours occurred in one of the sagittal or oblique injury groups but was present in 20 of the laterally injured animals, all of which were severely disabled afterward. All laterally injured animals had a degree of DAI similar to that found in severe human head injury. Coma lasting 16 minutes to 6 hours occurred in 2 of 13 of the sagittal group, 4 of 6 in the oblique group, and 4 of 26 in the lateral group, these animals had less neurological disability and less DAI than when coma lasted longer than 6 hours. These experimental findings duplicate the spectrum of traumatic coma seen in human beings and include axonal damage identical to that seen in sever head injury in humans. Since the amount of DAI was directly proportional to the severity of injury (duration of coma and quality of outcome), we conclude that axonal damage produced by coronal head acceleration is a major cause of prolonged traumatic coma and its sequelae.Annals of Neurology 01/1983; 12(6):564-74. · 11.19 Impact Factor