Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)




College of Graduate Studies

First Advisor

DeAnna L. Adkins

Second Advisor

Andy Shih

Third Advisor

Colleen A. Hanlon

Fourth Advisor

Jens H. Jensen

Fifth Advisor

Rick Schnellmann


The primary goal of these studies is to enhance recovery of motor function following stroke and to understand the relationship between dMRI measures and the cellular, functional, and behavioral changes acutely and chronically following rehabilitation. We hypothesize that dMRI will be a sensitive tool to identify microstructural changes acutely and chronically following stroke and that promoting mitochondria biogenesis will lead to better functional recovery and induce structural and functional plasticity following rehabilitative training. Towards this goal, we used a combination of sensitive behavioral, immunohistochemical and mitochondrial-related molecular markers, and diffusion magnetic resonance imaging (dMRI) to investigate the time course of acute and chronic stroke effects. We were able to detect acute changes in dMRI metrics and correlate those changes with functional and morphological plasticity following stroke. Our work has shown that mean kurtosis, a dMRI metric, increased acutely after stroke and persists days poststroke in the lesion core. We found strong correlations between mean diffusivity and astrogliosis in the perilesional stroke area. There were no correlations between dendritic and axonal surface densities and dMRI metrics acutely following stroke. However, behavioral-induced and learning-induced neural plasticity was not detected with dMRI changes chronically in perilesional grey matter or white matter. Our studies have revealed mitochondria dysfunction that persists for at least six days post stroke in ipsilesional cortex and striatum following a focal sensorimotor (SMC) ischemic lesion. Therefore, we proposed that pharmacologically enhancing mitochondria function and biogenesis would promote recovery after stroke when administered early after stroke. We found that giving a drug known to induce mitochondria biogenesis, formoterol, a FDA approved long-lasting β2-adrenergic receptor agonist, twenty-four hours after SMC ischemic lesions caused a full restoration of markers of mitochondria function in the striatum three days post stroke and stimulates a partial recovery of functional markers in the cortex six days post-stroke. Our studies revealed that animals given formoterol (0.1mg/kg) combined with motor rehabilitative training (RT) daily for 15 days leads to better recovery of motor function than animals given vehicle treatment and RT. These data demonstrate that stimulating mitochondria biogenesis acutely after stroke enhances functional motor recovery.


All rights reserved. Copyright is held by the author.