Affiliations: [a]
Department of Neurological Surgery, Vanderbilt University, Nashville, TN, USA
| [b]
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA
| [c] San Bio, Inc. Mountain View, California, CA, USA
| [d]
Department of Physical Medicine and Rehabilitation, University of Kansas Medical Center, Kansas City, Kansas, KS, USA | [e]
Department of Neurological Surgery, Mount Sinai Health, New York, NY, USA
Correspondence:
[*]
Corresponding author: J. Mocco, Klingenstein Clinical Center. 1 North 1450 Madison Avenue, New York, NY 10029, USA. E-mail: j.mocco@mountsinai.org.
Abstract: Hematopoietic stem cells (HSC) are recruited to ischemic areas in the brain and contribute to improved functional outcome in animals. However, little is known regarding the mechanisms of improvement following HSC administration post cerebral ischemia. To better understand how HSC effect post-stroke improvement, we examined the effect of HSC in ameliorating motor impairment and cortical dysfunction following cerebral ischemia. Methods:Baseline motor performance of male adult rats was established on validated motor tests. Animals were assigned to one of three experimental cohorts: control, stroke, stroke + HSC. One, three and five weeks following a unilateral stroke all animals were tested on motor skills after which intracortical microstimulation was used to derive maps of forelimb movement representations within the motor cortex ipsilateral to the ischemic injury. Results:Stroke + HSC animals significantly outperformed stroke animals on single pellet reaching at weeks 3 and 5 (28±3% and 33±3% versus 11±4% and 17±3%, respectively, p < 0.05 at both time points). Control animals scored 44±1% and 47±1%, respectively. Sunflower seed opening task was significantly improved in the stroke + HSC cohort versus the stroke cohort at week five-post stroke (79±4 and 48±5, respectively, p < 0.05). Furthermore, Stroke + HSC animals had significantly larger forelimb motor maps than animals in the stroke cohort. Overall infarct size did not significantly differ between the two stroked cohorts. Conclusion:These data suggest that post stroke treatment of HSC enhances the functional integrity of residual cortical tissue, which in turn supports improved behavioral outcome, despite no observed reduction in infarct size.
