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Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Purpose: An injury to the forelimb sensorimotor cortex results in the impairment of motor function in animals. Recent research has suggested that intranasal administration of nerve growth factor (NGF), a protein naturally found in the brain, and placement into enriched environments (EE) improves motor and cognitive function after traumatic brain injury (TBI). The purpose of this study was to determine whether NGF, EE, or the combination of both was beneficial in the recovery of motor function following TBI., Results: Uninjured animals had fewer foot faults than injured animals, displaying a lesion effect. Injured animals housed in EE were shown to have fewer foot faults whether or not they received NGF. Injured animals also displayed an increased reliance on the non-impaired limb further validating a lesion effect., Conclusion: EE is an effective treatment on the recovery of motor function after a TBI. Intranasal administration of NGF was found to not be an effective treatment for functional motor recovery after a TBI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II-III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Previous studies demonstrated that administering extradural cortical stimulation (ECS) to rats during the acute phase of a photothrombotic infarct enhances motor recovery. However, the effect of ECS during the subacute phase was unknown. We aimed to evaluate the effects of ECS on motor recovery in a rat model of subacute photothrombotic stroke., Methods: Photothrombotic ischemic injury to the left sensorimotor cortex (SMC) was induced in 41 male Sprague-Dawley rats using Rose-bengal dye (20 mg/kg) and cold light. The rats were randomly divided into two groups: ECS on infarcted SMC (ECS group) and no ECS on infarcted SMC (non-stimulated group). The ECS group received continuous ECS for 14 days starting from day 5 after the stroke onset. Behavioral training with the single-pellet reaching task (SPRT) was performed daily for all of the rats from the fifth day after stroke onset. After 19 days, brain sections were immunostained to allow the quantification of infarct volumes and the evaluation of the neuronal markers., Results: The SPRT scores showed significantly faster and greater improvement in the ECS group than in the non-stimulated group. There were no significant differences in infarct size. However, in the ECS group, significantly more doublecortin-labeled cells were identified close to the penumbra region of the cerebral cortex., Conclusions: ECS in the subacute phase improved the behavior motor function in the stroke rat model, and induced a significant axonal sprouting in the peri-infarct area.