Subcutaneous injection of carbachol enhances brain graft-induced recovery of memory-function by circumventing the blood-brain barrier.

After bilateral neurotoxic hippocampectomy adult rats received bilateral fetal suspension grafts at the lesion sites. Functional efficacy of fetal grafted tissue was substantially improved by subcutaneous administration of carbachol at a dose of 0.01 mg/kg s.c. The drug caused an almost complete restitution of performance in grafted animals in a Morris water-maze test. The progress of behavioral recovery was studied over 3 months postoperatively. Grafts of fetal hippocampal neurons alone improved lesion-induced spatial learning deficits to a limited degree. These results suggest that peripheral administration of carbachol may be of use in the treatment of central lesions associated with cognitive impairments, allowing or enhancing the development of graft-induced amelioration of behavioral deficits. The data also support the view that grafts of embryonic neural tissue may produce a local opening of the blood-brain barrier allowing drugs which normally act only peripherally to exert central effects. These central effects are probably limited to the graft site because the rest of the brain has a blood-brain barrier which is still intact.