Qin Lai

Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin

There is increasing evidence that physical activity is associated with a decreased stroke risk. The purpose of this study was to determine if exercise could also reduce brain damage in rats subjected to transient middle cerebral artery (MCA) occlusion, and if the reduced brain injury is associated with angiogenesis as well as cellular expression of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in regions supplied by the MCA. Adult male Sprague Dawley rats (n=36) exercised 30 min each day for 3 weeks on a treadmill on which repetitive locomotor movement was required. Then, stroke was induced by a 2-h MCA occlusion using an intraluminal filament, followed by 48 h of reperfusion. In addition to the two exercised groups of animals with or without MCA occlusion, there were two other groups of animals, with or without MCA occlusion, housed for the same duration and used as non-exercised controls. Brain damage in ischemic rats was evaluated by neurologic deficits and infarct volume. Exercise preconditioned and non-exercised brains were processed for immunocytochemistry to quantify the number of microvessels or NGF- and BDNF-labeled cells. Pre-ischemic motor activity significantly (P<0.01) reduced neurologic deficits and infarct volume in the frontoparietal cortex and dorsolateral striatum. Cellular expressions of NGF and BDNF were significantly (P<0.01) increased in cortex (neuron) and striatum (glia) of rats under the exercise condition. Significant (P<0.01) increases in microvessel density were found in striatum. Physical activity reduced stroke damage. The reduced brain damage may be attributable to angiogenesis and neurotrophin overexpression in brain regions supplied by the MCA following exercise.

Spacing practice sessions across days benefits the learning of motor skills

The effects of distributing practice sessions across days, compared to within days, on the learning of motor skills were examined. In Experiment 1, a continuous dynamic balance task was practiced in two sessions of seven trials each. For one group, sessions were separated by 20 min while for the other group the sessions were separated by 24 h. In Experiment 2, three variations of a key-press timing task were practiced in three sessions, one session for each task variation. Again, practice for one group was distributed within days and the other across days. In both experiments, a retention test was administered 24 h after the completion of practice. The results indicated that spacing practice sessions over relatively long intervals (days) resulted in the enhancement of performance during the remaining practice sessions and enhanced learning as assessed by the delayed retention test. The results are consistent with the memory consolidation hypothesis and suggest that this interval may play a substantial role in the learning of motor skills.

Generalized Motor Program (GMP) Learning: Effects of Reduced Frequency of Knowledge of Results and Practice Variability.

The effects of reduced frequency of presentation of relative-liming knowledge of results (KR) on constant and serial practice and whether response stability is associated with increased generalized motor program (GMP) learning were examined. Participants (N = 40) were asked to sequentially depress 4 keys (2, 4, 8, and 6) on the numeric pad portion of the computer keyboard by using the index fingers of their right hands. The frequency (50% and 100%) with which relative-timing KR was presented was manipulated in constant and in serial practice conditions. The tasks used in both the constant and the serial conditions had the same relative-timing structure, but serial practice had 3 different absolute-timing requirements. The results, which indicated that reduced KR frequency enhances GMP learning in the serial practice condition, replicate the findings of Wulf, Lee, and Schmidt (1994). The reduced frequency of KR effect was not evident for the constant practice groups, however. More interesting was the finding that constant practice was significantly better than serial practice for the development and learning of the GMP. The data also showed that after either constant practice or reduced frequency of KR, response stability was enhanced in comparison with the stability of responses following serial practice and frequent KR. Those findings suggest that when response stability is improved either by reducing the frequency with which KR is presented or by reducing the number of task variations practiced, the development of the GMP is enhanced but parameter specification in transfer tasks tends to be degraded.

Increased astrocyte proliferation in rats after running exercise

The aim in this study was to investigate whether physical exercise could induce astroglial proliferation in the frontoparietal cortex and dorsolateral striatum where extensive angiogenesis had been found after exercise in previous studies. Adult male Sprague Dawley rats (n=48) were used in four experimental groups. Animals were exercised 30 min each day on a treadmill on which repetitive locomotor movement was required, for 0 (n=12), 3 (n=12) or 6 (n=12) weeks, as well as 3-week exercise plus 3-week rest (n=12). Brain tissues of the exercised and non-exercised rats were processed for glial fibrillary acidic protein (GFAP) immunocytochemistry (n=6 x 4) and Western blotting (n=6 x 4) to evaluate regional astrocyte proliferation in the frontoparietal cortex and dorsolateral striatum. By using GFAP immunocytochemistry and stereological methods, we compared the density of astrocytes in the animals with or without exercise. In comparison to non-exercised animals, a significant (p<0.01) increase in the number of astrocytes was observed in both cortex and striatum of rats exercised for 3 or 6 weeks. Our data also indicated that astrocytic density continued to increase up to 6 weeks either with an additional 3 weeks of exercise (p<0.01) or 3 weeks of rest (p<0.01). In addition, Western blotting analysis showed an obvious increase in GFAP protein from cortex and striatum of exercised animals. Astrocytosis after exercise, coupled with angiogenesis, is thought to provide strength to the neurovascular unit (a construct consisting of microvascular endothelium, astroglia, neurons and the extracellular matrix). Strengthening of this unit by exercise may protect blood-brain-barrier function following brain injury, such as that occurring after stroke.

Consistent and Variable Practice Conditions: Effects on Relative and Absolute Timing

Abstract The authors conducted the present experiments to resolve the discrepancy between studies in which relative-timing learning has been found to be enhanced by consistent practice conditions and contextual interference experiments in which relative-timing learning has been found to be enhanced more by random practice than by blocked practice. There were 40 participants in Experiment 1 and 48 in Experiment 2. The results of Experiment 1 extended previous findings: The learning of the relative-timing pattern was systematically enhanced by the degree to which the practice conditions promoted movement consistency (constant > blocked > serial > random). Experiment 2 provided evidence that the discrepancy between the relative-timing effects in the 2 groups of studies was a product of the way in which relative-timing goals and feedback were presented. When the feedback was presented as segment times, random practice resulted in generally more stable relative-timing patterns during acquisition than blocked practice did. Thus, in both experiments, the learning of the relative-timing pattern was enhanced by more stable relative-timing conditions during acquisition. Absolute-timing learning, as indexed by the transfer tests, was enhanced by serial or random practice as compared with constant or blocked practice, and was relatively unaffected by feedback conditions directed at the relative-timing pattern. In terms of motor programming theory, those findings are taken as additional evidence for the disassociation of memories supporting generalized motor program (GMP) performance, as indexed by relative timing, and parameter performance, as indexed by absolute timing.

Motor balance and coordination training enhances functional outcome in rat with transient middle cerebral artery occlusion

The goal of this study was to determine if relatively complex motor training on Rota-rod involving balance and coordination plays an essential role in improving motor function in ischemic rats, as compared with simple locomotor exercise on treadmill. Adult male Sprague-Dawley rats with (n=40) or without (n=40) ischemia were trained under each of three conditions: (1) motor balance and coordination training on Rota-rod; (2) simple exercise on treadmill; and (3) non-trained controls. Motor function was evaluated by a series of tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and at 14 or 28 days after training procedures in both ischemic and normal animals. Infarct volume in ischemic animals was determined with Nissl staining. Compared with both treadmill exercised and non-trained animals, Rota-rod-trained animals with or without ischemia significantly (P<0.01) improved motor performance of all tasks except for foot fault placing after 14 days of training, with normal rats having better performance. Animals trained for up to 28 days on the treadmill did not show significantly improved function. With regard to foot fault placing task, performance on foot placing was improved in ischemic rats across the three measurements at 0, 14 and 28 days regardless of training condition, while the normal group reached their best performance at the beginning of measurement. No significant differences in infarct volume were found in rats trained either with Rota-rod (47+/-4%; mean+/-S.E.), treadmill (45+/-5%) or non-exercised control (45+/-3%). In addition, no obvious difference could be detected in the location of the damage which included the dorso-lateral portion of the neostriatum and the frontoparietal cortex, the main regions supplied by the middle cerebral artery. The data suggest that complex motor training rather than simple exercise effectively improves functional outcome.

Long-term neuroprotective effect of inhibiting poly(ADP-ribose) polymerase in rats with middle cerebral artery occlusion using a behavioral assessment

Poly(ADP-ribose) polymerase (PARP) can initiate an energy-consuming and inefficient repair cycle following cerebral ischemia/reperfusion by transferring ADP ribose units to nuclear proteins eventually leading to cellular dysfunction and neuronal death. 3-Aminobenzamide (3-AB) is a selective inhibitor of PARP that can significantly reduce brain damage after focal ischemia in rats and displays a low toxicity in vivo. The goals of this study were to determine if inhibiting PARP with 3-AB has a long-term neuroprotective effect and if functional outcome improves in rats following focal ischemia and treatment with 3-AB. Focal ischemia was induced by a 2-h occlusion of the middle cerebral artery (MCA), using an intraluminal filament. Motor functions were evaluated from 5 to 28 days after reperfusion in four groups of rats: stroke without treatment; stroke treated with 3-AB at doses of 15 mg/kg, stroke treated with 3-AB at doses of 55 mg/kg; and the non-ischemic control rats. Functional behaviors were tested by a series of motor function tasks (foot placing, parallel bar crossing, rope and ladder climbing), as well as a neurological examination. Infarct volume of stroke brain in the same rat was determined by Nissl staining 28 days after surgery. Comparison of the untreated stroke group (n=11) and the treated stroke groups indicates that impairment of motor function was significantly (P<0.001) reduced by administration of 3-AB at doses of 15 mg/kg (n=9) or 55 mg/kg (n=10). Neurological outcome was also improved significantly (P<0.001). Infarct volume was significantly (P<0.01) reduced in both treated groups. Long-term neuroprotection following ischemia/reperfusion injury to the brain can be obtained by administration of a PARP inhibitor. The motor tests employed in this study can be used as sensitive, objective and reproducible measurements of functional impairment in rats following an ischemic stroke.

Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion.

OBJECTIVEThe neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole-body surface cooling, has been limited primarily because of management problems and severe side effects (e.g., pneumonia). The goal of this study was to determine whether local infusion of saline into ischemic territory could induce regional brain cooling and neuroprotection. METHODSA novel procedure was used to block the middle cerebral artery of rats for 3 hours with a hollow filament and locally infuse the middle cerebral artery-supplied territory with 6 ml cold saline (20°C) for 10 minutes before reperfusion. RESULTSThe cold saline infusion rapidly and significantly reduced temperature in cerebral cortex from 37.2 ± 0.1 to 33.4 ± 0.4°C and in striatum from 37.5 ± 0.2 to 33.9 ± 0.4°C. The significant hypothermia remained for up to 60 minutes after reperfusion. Significant (P < 0.01) reductions in infarct volume (approximately 90%) were evident after 48 hours of reperfusion. In ischemic rats that received the same amount of cold saline systemically through a femoral artery, a mild hypothermia was induced only in the cerebral cortex (35.3 ± 0.2°C) and returned to normal within 5 minutes. No significant reductions in infarct volume were observed in this group or in the ischemic group with local warm saline infusion or without infusion. Furthermore, brain-cooling infusion significantly (P < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion. This improvement continued for up to 28 days after reperfusion. CONCLUSIONLocal prereperfusion infusion effectively induced hypothermia and ameliorated brain injury from stroke. Clinically, this procedure could be used in acute stroke treatment, possibly in combination with intra-arterial thrombolysis or mechanical disruption of clot by means of a microcatheter.

Impaired motor learning and diffuse axonal damage in motor and visual systems of the rat following traumatic brain injury

Abstract Cognitive-motor functioning or motor skill learning is impaired in humans following traumatic brain injury. A more complete understanding of the mechanisms involved in disorders of motor skill learning is essential for any effective rehabilitation. The specific goals of this study were to examine motor learning disorders, and their relationship to pathological changes in adult rats with mild to moderate closed head injury. Motor learning deficits were determined by comparing the ability to complete a series of complex motor learning tasks with simple motor activity. The extent of neuronal damage was determined using silver impregnation. At all post-injury time points (day 1 to day 14), statistically significant deficits were observed in parallel bar traversing, foot placing, ladder climbing, and rope climbing. Performance improved with time, but never reached control levels. In contrast, no deficits were found in simple motor activity skills tested with beam balance and runway traverse. Histologically, axonal degeneration was widely distributed in several brain areas that relate to motor learning, including the white matter of sensorimotor cortex, corpus callosum, striatum, thalamus and cerebellum. Additionally, severely damaged axons were observed in the primary visual pathway, including the optic chiasm, optic tract, lateral geniculate nuclei, and superior colliculus. These findings suggest that motor learning deficits could be detected in mild or moderate brain injury, and this deficit could be attributed to a diffuse axonal injury distributed both in the motor and the visual systems. [Neurol Res 2001; 23: 193-202]

The Role of Reduced Frequency of Knowledge of Results during Constant Practice

Two experiments were conducted to further examine the effects of reduced knowledge of results (KR) frequency on the learning of motor skills during constant practice. In Experiment 1, participants in five KR conditions (100% KR, 50% KR-fade, 50% KR-reverse fade, 50% KR-alternative, and 50% KR-random) practiced a movement timing task. In Experiment 2, participants in two KR conditions (100% KR and 50% KR-fade) practiced a waveform reproduction task. The results of both experiments failed to indicate that reduced KR frequency was more effective in promoting learning than the 100% KR conditions. The present study adds to the increasing number of experiments that do not find a benefit of reduced KR frequency on learning in constant practice.