Characterizing Spontaneous Motor Recovery Following Cortical and Subcortical Stroke in the Rat

Abstract

Background. Stroke is a leading cause of neurological disability, often resulting in long-term motor impairments due to damage to cortical or subcortical motor areas. Despite the high prevalence of subcortical strokes in the clinical population, preclinical research has primarily focused on investigating and treating cortical strokes. Moreover, while both humans and animals show spontaneous recovery following stroke, little is known about how injury location affects this process. Objective. To capture the heterogeneity of human stroke and examine how stroke location affects spontaneous motor recovery following damage to cortical, subcortical, or a combination of both areas. Methods. Endothelin-1 (ET-1), a potent vasoconstrictor, was used to produce focal infarcts in the forelimb motor cortex (FMC), the dorsolateral striatum (DLS) or both the FMC and DLS in male Sprague-Dawley rats. The spontaneous recovery profile of animals was followed over an 8-week period using a battery of behavioral tasks assessing motor function and limb preference. Results. All 3 groups showed significant impairments on the Montoya staircase, beam, and cylinder tests following stroke, with the combined group (FMC + DLS) having the largest and most persistent impairments. Importantly, spontaneous recovery was not simply dependent on lesion volume, but on location, and the behavioral test employed. Conclusions. Stroke location markedly and differentially influences the level of spontaneous functional recovery, which is only captured by using multiple outcome measures. These results illustrate the need for preclinical stroke models to align with the heterogeneity of human stroke, especially with respect to lesion location, size, and outcome measures.

Poststroke Impairment and Recovery Are Predicted by Task-Specific Regionalization of Injury

“…This combination of biomarkers more accurately predicted final outcome than initial impairment alone, including animals with profound impairments (Jeffers et al, 2018b). In a subsequent rodent study, the extent of poststroke impairment and recovery varied in relation to both cortical versus subcortical lesion location and the functional domain assessed (Karthikeyan et al, 2019), suggesting that lesion location may influence the level of recovery. In humans, both lesion location and volume have been shown to affect recovery (Chen et al, 2000), but volume, without consideration for location, is a relatively poor predictor of recovery (Chen et al, 2000;Page et al, 2013).…”

Compensatory Relearning Following Stroke: Cellular and Plasticity Mechanisms in Rodents

“…It is still to be answered if this is the case for skilled trained animals, and also for post-stroke reemergence and reorganization of motor maps. In a recent study, it was shown that striatal lesions are important for spontaneous recovery of non-skilled tasks (i.e., cylinder task) but not for dexterous reaching behavior (i.e., staircase task) (Karthikeyan et al, 2018). This is in accordance with the emerging consensus on the concept of cortical control over skilled motor behavior (Papale and Hooks, 2018).…”

Intermittent Skill Training Results in Moderate Improvement in Functional Outcome in a Mouse Model of Ischemic Stroke

“…However, the tasks were untrained assessments of motor performance (eg, cylinder test, hanging wire test, pole test, and adhesive removal test), which typically show fewer deficits and more spontaneous recovery than skilled reaching tasks. 28 The animals in the study by Li et al 27 were also tested up to 8 weeks poststroke, and the majority of group differences were seen at this time point. According to these data, the Control mice in the present study should not demonstrate significant spontaneous recovery given that only 2 weeks of poststroke behavior were assessed.…”