Dataset Information

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

ABSTRACT:

Unlabelled

Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH.

Significance statement

The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the effect of intensive limb use.

SUBMITTER: Ishida A

PROVIDER: S-EPMC4710769 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

Ishida Akimasa A Isa Kaoru K Umeda Tatsuya T Kobayashi Kazuto K Kobayashi Kenta K Hida Hideki H Isa Tadashi T

The Journal of neuroscience : the official journal of the Society for Neuroscience 20160101 2

PMID: 26758837

Similar Datasets

Project description:Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH.SIGNIFICANCE STATEMENT This study aimed to clarify the interaction between the cortico-rubral and the cortico-reticular tract during intensive rehabilitation and functional recovery after capsular stroke. Pathway-selective disturbance by two sets of viral vectors revealed that the cortico-rubral tract was involved in rehabilitation-induced recovery of forelimb function from an early phase after internal capsule hemorrhage, but that the cortico-reticular tract was not. The sequential disturbance of both tracts revealed that the cortico-reticular tract was recruited and involved in rehabilitation-induced recovery when the cortico-rubral tract failed to function. Our data demonstrate a dynamic compensatory action of individual cortico-brainstem pathways for recovery through poststroke rehabilitation.

Project description:BackgroundSince birth, during the exploration of the environment to interact with objects, we exploit both the motor and sensory components of the upper limb (UL). This ability to integrate sensory and motor information is often compromised following a stroke. However, to date, rehabilitation protocols are focused primarily on recovery of motor function through physical therapies. Therefore, we have planned a clinical trial to investigate the effect on functionality of UL after a sensorimotor transcranial stimulation (real vs sham) in add-on to robot-assisted therapy in the stroke population.MethodsA randomised double-blind controlled trial design involving 32 patients with a single chronic stroke (onset > 180 days) was planned. Each patient will undergo 15 consecutive sessions (5 days for 3 weeks) of paired associative stimulation (PAS) coupled with UL robot-assisted therapy. PAS stimulation will be administered using a bifocal transcranial magnetic stimulator (TMS) on the posterior-parietal cortex and the primary motor area (real or sham) of the lesioned hemisphere. Clinical, kinematics and neurophysiological changes will be evaluated at the end of protocol and at 1-month follow-up and compared with baseline. The Fugl-Meyer assessment scale will be the primary outcome. Secondly, kinematic variables will be recorded during the box-and-block test and reaching tasks using video analysis and inertial sensors. Single pulse TMS and electroencephalography will be used to investigate the changes in local cortical reactivity and in the interconnected areas.DiscussionThe presented trial shall evaluate with a multimodal approach the effects of sensorimotor network stimulation applied before a robot-assisted therapy training on functional recovery of the upper extremity after stroke. The combination of neuromodulation and robot-assisted therapy can promote an increase of cortical plasticity of sensorimotor areas followed by a clinical benefit in the motor function of the upper limb.Trial registrationClinicalTrials.gov NCT05478434. Registered on 28 Jul 2022.

Project description:Background: Research imaging costs limit lesion-based analyses in already expensive large stroke rehabilitation trials. Despite the belief that lesion characteristics influence recovery and treatment response, prior studies have not sufficiently addressed whether lesion features are an important consideration in motor rehabilitation trial design. Objective: Using clinically-obtained neuroimaging, evaluate how lesion characteristics relate to upper extremity (UE) recovery and response to therapy in a large UE rehabilitation trial. Methods: We reviewed lesions from 297 participants with mild-moderate motor impairment in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study and their association with motor recovery, measured by the UE Fugl-Meyer (UE-FM). Significant lesion features identified on correlational and bivariate analysis were further analyzed for associations with recovery and therapy response using longitudinal mixed models. Results: Prior radiographic stroke was associated with less recovery on UE-FM in participants with motor impairment from subsequent subcortical stroke (-5.8 points) and in the overall sample (-3.6 points), but not in participants with cortical or mixed lesions. Lesion volume was also associated with less recovery, particularly after subcortical stroke. Every decade increase in age was associated with 1 less point of recovery on UE-FM. Response to specific treatment regimens varied based on lesion characteristics. Subcortical stroke patients experienced slightly less recovery with higher doses of upper extremity task-oriented training. Participants with cortical or mixed lesions experienced more recovery with higher doses of usual and customary therapy. Other imaging features (leukoaraiosis, ischemic vs. hemorrhagic stroke) were not significant. Conclusions: ICARE clinical imaging revealed information useful for UE motor trial design: stratification of persons with and without prior radiographic stroke may be required in participants with subcortical stroke, the majority of motor rehabilitation trial participants. Most of the prior radiographic strokes were small and cortically-based, suggesting even minor prior brain injury remote to the acute stroke lesion may limit spontaneous and therapy-related recovery. Lesion location may be associated with response to different therapy regimens, but the effects are variable and of unclear significance.

Project description:Background and purposeEarly studies have indicated that the cortico-rubro-spinal tracts play important roles in motor dysfunction after stroke. However, the differential involvement of the rubral branches in capsular and pontine stroke, and their associations with the motor impairment are still unknown.MethodsThe present study recruited 144 chronic stroke patients and 91 normal controls (NC) from three hospitals, including 102 cases with capsular stroke (CS) and 42 cases with pontine stroke (PS). The rubral branches, including bilateral corticorubral tracts (CRT), dentatorubral tracts (DRT), and rubrospinal tracts (RST), and the cortico-spinal tract (CST) were reconstructed based on the dataset of the Human Connectome Project. Group differences in diffusion scalars of each rubral branch were compared, and the associations between the diffusion measures of rubral branches and the Fugl-Meyer assessment (FMA) scores were tested.ResultsThe bilateral CRT of the CS cases showed significantly lower factional anisotropy (FA) than in the NC. The bilateral DRT of the PS cases had lower FA than in the NC. Both CS and PS cases had significantly lower FA of the bilateral RST than the NC. Besides, the stroke patients demonstrated significantly lower FA in bilateral CSTs than the NC. Partial correlation analysis identified significantly positive correlations between the FA of the ipsilesional and CRT and the FMA scores in the CS group, and significantly positive correlations between the FA of the RST bilaterally and the FMA scores in the CS and PS groups. Furthermore, the association between RST integrity and FMA scores still survived after controlling for the effect of the CST. Finally, multiple regression modelling found that rubral tract FA explained 39.2% of the variance in FMA scores for CS patients, and 48.8% of the variance in FMA scores for PS patients.ConclusionsThe bilateral rubral branches were differentially involved in the chronic capsular and pontine stroke, and the impairment severity of each rubral branch was dependent on lesion locations. The integrity of the rubral branches is related to motor impairment in both the chronic capsular and pontine stroke.

Dataset Information

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

Unlabelled

Significance statement

Publications

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets