Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells

Background and Purpose-Grafts of,MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy af ter focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient i ntraluminal middle cerebral artery occlusion (tMCAO) in rats. Methods-MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 muL of cell suspension (25 000 cells per micr oliter). Sham grafted mts received equivalent volumes of vehicle. Three gro ups, sham-operated controls (n=11), MCAO+ sham grafts (n=10), and MCAO+MHP3 6 grafts (n=11), were compared in 3 behavioral tests. Results-In the bilateral asymmetry test? MCAO+MHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAO+sham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAO+sham grafted rats demonstrated spontaneou s motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either sponta neous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 g rafted rats showed no improvement relative to MCAO+sham grafted rats in spa tial learning and memory in the water maze. MCAO produced large striatal an d cortical cavitations in both occluded groups. Lesion volume was significa ntly reduced (P<0.05) in the MCAO+MHP36 grafted group. The majority of,MHP3 6 cells were identified within the intact grafted hemisphere. However, MHP3 6 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere. Conclusions-MHP36 cells may improve functional outcome after MCAO by assist ing spontaneous reorganization in both the damaged and intact hemispheres.