Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions

We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF.