Sprouting of brainstem-spinal tracts in response to unilateral motor cortex stroke in mice.

After a stroke to the motor cortex, sprouting of spared contralateral corticospinal fibers into the affected hemicord is one mechanism thought to mediate functional recovery. Little is known, however, about the role of the phylogenetically old, functionally very important brainstem-spinal systems. Adult mice were subjected to a unilateral photothrombotic stroke of the right motor cortex ablating 90% of the cross-projecting corticospinal cells.

Rewiring of the corticospinal tract in the adult rat after unilateral stroke and anti-Nogo-A therapy.

Adult Long Evans rats received a photothrombotic stroke that destroyed >90% of the sensorimotor cortex unilaterally; they were subsequently treated intrathecally for 2 weeks with a function blocking antibody against the neurite growth inhibitory central nervous system protein Nogo-A. Fine motor control of skilled forelimb grasping improved to 65% of intact baseline performance in the anti-Nogo-A treated rats, whereas control antibody treated animals recovered to only 20% of baseline scores. Bilateral retrograde tract tracing with two different tracers from the intact and the denervated side of the cervical spinal cord, at different time points post-lesion, indicated that the intact corticospinal tract had extensively sprouted across the midline into the denervated spinal hemicord.

Deep brain stimulation of the midbrain locomotor region improves paretic hindlimb function after spinal cord injury in rats.

In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center for locomotion in the brain, markedly improved hindlimb function in rats with chronic, severe, but incomplete spinal cord injury. The medial medullary reticular formation was essential for this effect.

Back seat driving: hindlimb corticospinal neurons assume forelimb control following ischaemic stroke.

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur.