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.
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 humanstroke 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 humanstroke, especially with respect to lesion location, size, and outcome measures.
Entities:
Keywords:
animal models; endothelin-1; functional recovery; motor cortex; striatum; stroke
Authors: Matthew S Jeffers; Boris Touvykine; Allyson Ripley; Gillian Lahey; Anthony Carter; Numa Dancause; Dale Corbett Journal: J Neurosci Date: 2020-06-30 Impact factor: 6.167
Authors: Sergiy Chornyy; Aniruddha Das; Julie A Borovicka; Davina Patel; Hugh H Chan; John K Hermann; Thomas C Jaramillo; Andre G Machado; Kenneth B Baker; Hod Dana Journal: Biomed Opt Express Date: 2021-07-16 Impact factor: 3.732
Authors: Hardeep Ryait; Edgar Bermudez-Contreras; Matthew Harvey; Jamshid Faraji; Behroo Mirza Agha; Andrea Gomez-Palacio Schjetnan; Aaron Gruber; Jon Doan; Majid Mohajerani; Gerlinde A S Metz; Ian Q Whishaw; Artur Luczak Journal: PLoS Biol Date: 2019-11-21 Impact factor: 8.029