Factors affecting septal graft amelioration of differential reinforcement of low rates (DRL) and activity deficits after fimbria-fornix lesions

Abstract

Wound-derived trophic factors released by the injured brain are thought to reach a peak 1–2 weeks after injury. It has been proposed that such factors can promote the survival, growth and functional capacity of embryonic tissue grafts. To test the generality of this hypothesis, control rats and rats with aspirative fimbria-fornix lesions were compared with 5 groups of rats with lesions and septal grafts implanted either in the same session as the lesion or after delays from 10 days to 9 months. Animals were assessed 3 months post-transplantation on an operant differential reinforcement of low rates (DRL) task and on a test of spontaneous locomotor activity. Lesions produced impairments on all measures of DRL performance. Two graft groups showed amelioration of the DRL deficits, one graft group was unchanged, and the deficits were exacerbated in two others. There was no clear relationship between lesion–graft interval and recovery. An inverse relationship was seen, however, between recovery and the developmental age of the donor tissue. In contrast, significant recovery from lesion-induced hyperactivity was observed in the two graft groups with tissue derived from the oldest embryos. There were no clear relationships between recovery on either test, lesion–graft interval, and AChE-positive reinnervation of the host brain. The results provide further evidence that septal grafts can reverse behavioural deficits induced by fimbria-fornix lesions under some conditions, but suggest that the timing of graft surgery may not be as important a factor as donor age in this model system.