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Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behaviour within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke.

Rehabilitation, consisting of enriched environment and skilled reach training, improves recovery after intracerebral hemorrhage (ICH) in rats. We tested whether rehabilitation influences dendritic morphology (Golgi-Cox staining-experiment 1) or cell proliferation (immunohistochemistry-experiment 2). In the latter experiment, BrdU was given from 14 to 18 days post stroke, and cells were labeled for BrdU along with NeuN, Iba1 or GFAP. One week after a striatal ICH, via collagenase infusion, the rats were given rehabilitation for 2 weeks or control treatment (group housing in standard cages). Behavioral outcome (e.g., skilled reaching, walking) was assessed at multiple times. Rats were euthanized at 5 (experiment 2) or 6 (experiment 1) weeks post-ICH. As expected, rehabilitation significantly improved skilled reaching and walking ability. There was also a concomitant increase in dendritic length in peri-hematoma striatum and ipsilateral cortex as well as in the contralateral striatum. Lesion volume did not differ between groups, nor did cell proliferation. There was no evidence of neurogenesis, but there was increased Iba1 and GFAP labeling in the injured hemisphere. Thus, rehabilitation likely improves outcome after ICH though a plasticity response (e.g., increased dendritic growth) that does not involve neurogenesis.

Rehabilitation improves recovery after intracerebral hemorrhage (ICH) in rats. In some cases, brain damage is attenuated. In this study, we tested whether environmental enrichment (EE) combined with skilled reach training improves recovery and lessens brain injury after ICH in rats. Collagenase was injected stereotaxically to produce a moderate-sized striatal ICH. One week after ICH rats were either placed into a rehabilitation (REHAB) or control (CONT) condition. The REHAB rats received 15 h of EE and four 15-minute reach-training sessions daily over 5 days a week for 2 weeks. The CONT rats stayed in standard group cages. Skilled reaching (staircase test), walking (horizontal ladder) and forelimb use bias (cylinder test) were assessed at 4 and 6 weeks after ICH. Lesion volume, corpus callosum volume and cortical thickness were calculated 46 days after ICH. The REHAB treatment reduced lesion volume by 28% (p=0.019) without affecting the corpus callosum volume (p=0.405) or cortical thickness (p=0.300), thus indicating that protection was due to lessening striatal injury. As well, REHAB significantly improved skilled reaching ability in the staircase apparatus at 4 (p=0.002) and 6 weeks (p0.001) post-ICH. Transient benefit was obtained in the ladder test at 4 weeks (p=0.021). Unexpectedly, REHAB treatment lessened spontaneous use of the contralateral-to-ICH limb at 4 (p=0.045) and 6 weeks (p=0.041). In summary, the combination of EE and reach training significantly attenuates lesion volume (striatal injury) while improving skilled reaching and walking ability. These findings encourage the use of early rehabilitation therapies in patients suffering from basal ganglia hemorrhaging.

d -amphetamine (AMP) paired with physical activity (e.g., beam walking) improves recovery after ischemic injury to the cortical motor system of rodents. We tested whether AMP promotes recovery after intracerebral hemorrhage (ICH) in rats. A moderate-sized ICH was produced by stereotaxically injecting collagenase into the striatum. Five days later rats were placed into either environmental enrichment cages (EE) or a control condition (group housing in standard cages) until euthanasia at 4 weeks post-ICH. Animals were injected with either AMP (2 mg/kg i.p.) or sterile saline on days 7, 9 and 11 after ICH. Rats in EE also received training on beam (walking) and tray (skilled reaching) tasks 30 min after each injection. Walking (beam and ladder task), skilled reaching (tray and staircase tasks) and neurological deficits (NDS) were repeatedly assessed. We predicted that EE would improve recovery and that AMP would further enhance it. Results showed that EE, but not AMP, significantly and consistently improved recovery on the beam and ladder task. Neither treatment significantly affected skilled reaching. Lesion volume was not significantly different among groups (overall average: 44.6 mm3 of tissue lost ±15.3 S.D.). In conclusion, EE provides modest benefit for striatal ICH whereas AMP does not. This suggests that AMP will not provide substantial benefit to those patients with severe ICH affecting the basal ganglia.

Exercise can improve recovery following ischemia and intracerebral hemorrhage (ICH) in rodents. We tested whether forced exercise (EX; running wheel) prior to and/or following ICH in rats would reduce lesion volume and improve functional outcome (walking, skilled reaching, spontaneous paw usage) at 7 weeks post-ICH. A striatal hemorrhage was produced by infusing collagenase. First, we compared animals that received EX (2 weeks; 1 h/day) ending two days prior to ICH and/or starting two weeks following ICH. EX did not improve functional recovery or affect lesion size. Doubling the amount of EX given per day (two 1-h sessions) both prior to and following ICH did not alter lesion volume, but worsened recovery. We then determined if EX (1 h/day) prior to and following ICH would affect outcome after a somewhat milder insult. There were no differences between the groups in lesion volume or recovery. Finally, we used a hemoglobin assay at 12 h following ICH to determine if pre-stroke EX (2 weeks; 1 h/day) aggravated bleeding. It did not. These observations suggest that EX does not improve outcome when given prior to and/or when delayed following ICH. Effective rehabilitation for ICH will likely require more complex interventions than forced running.