Dataset Information

Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice.

ABSTRACT: Brain lesions caused by cerebral ischemia or hemorrhage lead to a local breakdown of energy homeostasis followed by irreversible cell death and long-term impairment. Importantly, local brain lesions also generate remote functional and structural disturbances, which contribute to the behavioral deficit but also impact the recovery of function. While spontaneous recovery has been associated with endogenous repair mechanisms at the vascular, neural, and immune cell levels, the impact of structural plasticity on sensory-motor dysfunction and recovery thereof remains to be elucidated by longitudinal imaging in a mouse model. Here, we applied behavioral assessments, in vivo fiber tracking, and histological validation in a photothrombotic stroke mouse model. Atlas-based whole-brain structural connectivity analysis and ex vivo histology revealed secondary neurodegeneration in the ipsilesional brain areas, mostly in the dorsal sensorimotor area of the thalamus. Furthermore, we describe for the first time a lesion size-dependent increase in structural connectivity between the contralesional primary motor cortex and thalamus with the ipsilesional cortex. The involvement of the contralesional hemisphere was associated with improved functional recovery relative to lesion size. This study highlights the importance of in vivo fiber tracking and the role of the contralesional hemisphere during spontaneous functional improvement as a potential novel stroke biomarker and therapeutic targets.

SUBMITTER: Aswendt M

PROVIDER: S-EPMC7803721 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice.

Aswendt Markus M Pallast Niklas N Wieters Frederique F Baues Mayan M Hoehn Mathias M Fink Gereon R GR

Translational stroke research 20200312 1

Brain lesions caused by cerebral ischemia or hemorrhage lead to a local breakdown of energy homeostasis followed by irreversible cell death and long-term impairment. Importantly, local brain lesions also generate remote functional and structural disturbances, which contribute to the behavioral deficit but also impact the recovery of function. While spontaneous recovery has been associated with endogenous repair mechanisms at the vascular, neural, and immune cell levels, the impact of structural ...[more]

PMID: 32166716

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Project description:BackgroundDespite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery.MethodsWe performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures.ResultsWe enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P=0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P=0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P=0.0494). There were no serious adverse events.ConclusionsTen daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center.RegistrationURL: https://trialsearch.who.int/; Unique identifier: NTR6133.

Dataset Information

Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice.

Publications

Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice.

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