Cerebral microhemorrhages impair gait coordination in mice

Abstract

Impairment in gait coordination and the consequent risk of falling are important problems in the rapidly aging population of the Western world: clinically diagnosable gait abnormalities affect approximately 35% of adults over age 70. While musculoskeletal mechanisms and processes have been extensively studied, factors affecting central neural control of gait coordination in older adults without overt neurological diseases are much less understood. Recent studies raise the possibility that in addition to causing cognitive decline, age‐associated cerebromicrovascular pathologies also contribute to mobility disability. However, the specific microvascular mechanisms underlying the loss of gait coordination in aging are not completely understood. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and cause focal disruption of neuronal networks. While there is growing evidence that CMHs predict cognitive impairment, the association between CMHs and gait abnormalities have not been investigated. The present study was designed to provide proof‐of‐concept that CMHs are causally linked to progressive gait dysfunction. To achieve this goal, we adapted a model of hypertension‐induced CMHs in mice (treatment with angiotensin II plus the NO synthase inhibitor L‐NAME). Computerized gait analysis was performed daily (Noldus CatWalk). CMHs were verified histologically. Mice with CMHs showed significantly altered gait function as measured by stride length, stride time and stride length variability, changes in phase‐dispersion and gait speed. CMH burden also correlated changes in the regularity index (a measure of inter‐paw coordination). Collectively, hypertension‐induced CMHs result in detectable impairment of gait function in mice. Further studies to analyze association of CMHs with gait abnormalities in human patients are warranted.Support or Funding InformationThis work was supported by grants from the American Heart Association, the National Center for Complementary and Alternative Medicine, and the National Institute on AgingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.