Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex.

Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats.

Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.

Low-speed treadmill running exercise improves memory function after transient middle cerebral artery occlusion in rats.

Physical exercise may enhance the recovery of impaired memory function in stroke rats. However the appropriate conditions of exercise and the mechanisms underlying these beneficial effects are not yet known. Therefore, the purpose of this study was to investigate the effect exercise intensity on memory function after cerebral infarction in rats. The animals were subjected to middle cerebral artery occlusion (MCAO) for 90 min to induce stroke and were randomly assigned to four groups; Low-Ex, High-Ex, Non-Ex and Sham. On the fourth day after surgery, rats in the Low-Ex and High-Ex groups were forced to exercise using a treadmill for 30 min every day for four weeks. Memory functions were examined during the last 5 days of the experiment (27-32 days after MCAO) by three types of tests: an object recognition test, an object location test and a passive avoidance test. After the final memory test, the infarct volume, number of neurons and microtubule-associated protein 2 (MAP2) immunoreactivity in the hippocampus were analyzed by histochemistry. Memory functions in the Low-Ex group were improved in all tests. In the High-Ex group, only the passive avoidance test improved, but not the object recognition or object location tests. Both the Low-Ex and High-Ex groups had reduced infarct volumes. Although the number of neurons in the hippocampal dentate gyrus of the Low-Ex and High-Ex groups was increased, the number for the Low-Ex group increased more than that for the High-Ex group. Moreover hippocampal MAP2 immunoreactivity in the High-Ex group was reduced compared to that in the Low-Ex group. These data suggest that the effects of exercise on memory impairment after cerebral infarction depend on exercise intensity.

Early onset of forced impaired forelimb use causes recovery of forelimb skilled motor function but no effect on gross sensory-motor function after capsular hemorrhage in rats.

Intensive use of the impaired forelimb promotes behavioral recovery and induces plastic changes of the central nervous system after stroke. However, the optimal onset of intensive use treatment after stroke is controversial. In this study, we investigated whether early forced impaired limb use (FLU) initiated 24h after intracerebral hemorrhage (ICH) of the internal capsule affected behavioral recovery and histological damage. Rats were subjected to ICH via low-dose collagenase infusion or sham stroke. One day after surgery, the ipsilateral forelimbs of half of the ICH and sham rats were casted for a week to induce the use of their contralateral forelimbs. Behavioral assessments were performed on days 10-12 and 26-28 after the surgery and followed by histological assessments. Improvements in skilled reaching and coordinated stepping function were found in the FLU-treated group in comparison with the untreated group after ICH. Additionally, FLU-treated ICH animals showed more normal and precise reaching and stepping movements as compared with ICH control animals. In contrast, FLU did not have a significant impact on gross sensory-motor functions such as the motor deficit score, contact placing response and spontaneous usage of the impaired paw. The volume of tissue lost and the number of spared corticospinal neurons in lesioned motor cortex were not affected by early FLU after ICH. These findings demonstrate the efficacy of early focused use of an impaired limb after internal capsule hemorrhage.