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Corbett, D.

Publications and source records attributed to Corbett, D..

2 recordsLinked to original sources

Sarcomere length, fascicle length, and serial sarcomere number are preserved in paretic hindlimb muscles following chronic stroke in rats despite persistent motor impairment

Stroke causes motor impairments that are commonly attributed to altered neural control, but chronic changes in neural activation and muscle use may also influence skeletal muscle structure. This study examined whether chronic stroke alters sarcomere length and dispersion, fascicle length, or serial sarcomere number in adult skeletal muscle. Twenty-four female Sprague-Dawley rats underwent photothrombotic stroke or sham surgery. Limb-specific motor impairment was assessed longitudinally using a beam traversal task. At 4.5 months post-surgery, the lateral gastrocnemius and extensor digitorum longus muscles were harvested from paretic and non-paretic limbs. We measured fascicle length directly from isolated fascicle bundles and quantified sarcomere length and dispersion using laser diffraction. Stroke animals exhibited persistent impairment of the paretic limb during beam traversal with elevated misstep rates. Despite this persistent motor impairment, sarcomere length and dispersion did not differ between stroke and sham animals or between limbs. Fascicle length and serial sarcomere number were greater in stroke than sham animals, but these differences were not limb-specific and were therefore unlikely to reflect stroke-related changes. Fascicle length, sarcomere length and dispersion, and serial sarcomere number differed between the lateral gastrocnemius and extensor digitorum longus, consistent with differences in architecture or relative length at the selected joint angles. These findings indicate that persistent neural impairment following adult-onset stroke does not necessarily result in substantial changes in sarcomere length or sarcomeres in series. Instead, sarcomere changes may depend on additional factors, including the timing of neural injury relative to growth and the mechanical environment experienced by the muscle.

physiology↗

CCR5 antagonists as neuroprotective and stroke recovery enhancing agents: a preclinical systematic review and meta-analysis

C-C chemokine receptor type 5 (CCR5) antagonists may improve both acute stroke outcome and long-term recovery. Despite their evaluation in ongoing clinical trials, gaps remain in the evidence supporting their use. With a panel of patients with lived experiences of stroke, we performed a systematic review of animal models of stroke that administered a CCR5 antagonist and assessed infarct size or behavioural outcomes. MEDLINE, Web of Science, and Embase were searched. Article screening and data extraction were completed in duplicate. We pooled outcomes using random effects meta-analyses. We assessed risk of bias using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool and alignment with the Stroke Treatment Academic Industry Roundtable (STAIR) and Stroke Recovery and Rehabilitation Roundtable (SRRR) recommendations. Five studies representing 10 experiments were included. CCR5 antagonists reduced infarct volume (standard mean difference -1.02; 95% confidence interval -1.58 to -0.46) when compared to stroke-only controls. Varied timing of CCR5 administration (pre- or post-stroke induction) produced similar benefit. CCR5 antagonists significantly improved 11 of 16 behavioural outcomes reported. High risk of bias was present in all studies and critical knowledge gaps in the preclinical evidence were identified using STAIR/SRRR. CCR5 antagonists demonstrate promise; however, rigorously designed preclinical studies that better align with STAIR/SRRR recommendations and downstream clinical trials are warranted. Prospective Register of Systematic Reviews (PROSPERO CRD42023393438).

neuroscience↗