EXPRESS: Stroke Is Associated with Temporally Ordered Neuromotor Dysfunction from Cortex to Muscle in a Translational Mouse Model
Arsh Ketabforoush, Meifang Wang, Vaibhav Oberoi, Charles Brennan, Gabriella Meier, Jose Viteri, Harper Snyder, Leena Suleiman, Ishan Pathak, Lixin Ma, Vaibhav Goswami, Ryan Castoro, William David ArnoldBackground:
Stroke is a major cause of long-term disability, yet the effects of cortical injury on downstream spinal and peripheral neuromuscular systems remain incompletely understood and have not been comprehensively evaluated in translational models. We aimed to longitudinally characterize post-stroke neuromotor dysfunction across cortical, spinal, and peripheral levels using clinically derived electrophysiological biomarkers in a mouse model of focal ischemia.
Methods:
Adult male C57BL/6J mice underwent 60-minute transient middle cerebral artery occlusion (tMCAO) or sham surgery. Electrophysiological assessments, including motor-evoked potentials (MEPs), H-reflexes, compound muscle action potentials (CMAP), and motor unit number estimation (MUNE), were performed at days 7 and 21 after stroke.
Results:
Stroke was associated with early suppression of infarct-side cortical output, reflected by reduced MEP amplitudes at day 7, while contralateral cortical excitability increased over time. Spinal excitability increased persistently after stroke and correlated with infarct size (r = 0.67, p = 0.024). At day 7, infarct-side MEP amplitudes were inversely associated with H-reflex (r = –0.66, p = 0.029). MUNE declined at day 7, followed by reduced CMAP amplitudes at day 21.
Conclusions:
Stroke was associated with temporally ordered neuromotor abnormalities across cortical, spinal, and peripheral systems, supporting a translational electrophysiological framework for testing recovery strategies.