Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells.
OBJECTIVE
Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats.


METHODS
MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 microL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (n=11), MCAO+sham grafts (n=10), and MCAO+MHP36 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 spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 grafted rats showed no improvement relative to MCAO+sham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (P<0.05) in the MCAO+MHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 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 assisting spontaneous reorganization in both the damaged and intact hemispheres.
ReNeuron Ltd, Department of Psychology, Institute of Psychiatry, King's College, London.
T
T
Veizovic
J S
JS
Beech
R P
RP
Stroemer
W P
WP
Watson
H
H
Hodges
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000637:transplantation*; D006085:Graft Survival; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D018782:Maze Learning; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D020521:Stroke / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D013696:Temperature; D016896:Treatment Outcome
D015259:Dopamine Agents; D000661:Amphetamine; D001058:Apomorphine