Contralesional axonal remodeling of the corticospinal system in adult rats after stroke and bone marrow stromal cell treatment.
OBJECTIVE
Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells.


METHODS
Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke.


RESULTS
In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P<0.05).


CONCLUSIONS
Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery.
Liu
Zhongwu
Z
Neurology Research, E&R Building, Room 3056, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Li
Yi
Y
Zhang
Xueguo
X
Savant-Bhonsale
Smita
S
Chopp
Michael
M
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives; D016026:Bone Marrow Transplantation / Q000379:methods*; D020520:Brain Infarction / Q000503:physiopathology / Q000628:therapy*; D001931:Brain Mapping; D003911:Dextrans; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality / Q000502:physiology; D011558:Herpesvirus 1, Suid; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009044:Motor Cortex / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D011712:Pyramidal Tracts / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation*
D003911:Dextrans; C076397:biotinylated dextran amine; D001710:Biotin