Targeting Cholinergic Neuromodulation in Stroke Recovery

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After ischemic stroke, patients can have significant deficits that limit their daily function. Most patients experience some degree of spontaneous recovery in the weeks after stroke. However, this recovery is often incomplete, and there are no treatment approaches which have been established to substantially restore lost function. Better functional assessment in the mouse model and investigation into controlling functional plasticity in the injured brain could each be key to producing better recovery in stroke patients. To work toward better functional assessment of stroke deficit and recovery in the mouse model, I developed an automated reach task in the mouse model that produces a longer lasting behavioral deficit after cortical infarct than most tests. A modified version of this test demonstrates that cortical ischemic stroke in the mouse recapitulates human-typical patterns of precise distal forelimb muscle control deficits. After developing, validating, and characterizing this task I used it to investigate the role of neuromodulation on stroke recovery. The results of these studies show that NB cholinergic cells in the mouse are necessary for typical recovery from stroke, and increasing their activation during successful rehabilitation movements may improve recovery.

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