Functional recovery from tactile stimulation after perinatal cortical injury is mediated by FGF-2

The consequences of perinatal brain injury can be devastating but currently there are few effective treatments. We sought to determine if tactile stimulation (TS) or exogenous application of fibroblast growth factor-2 (FGF-2) following injury could reverse the behavioral loss. Infant rats received frontal cortex removals on postnatal day 4 (P4) or a sham surgery. The TS animals received thrice-daily 15-minute bouts of stimulation (Experiment 1) on the day following surgery until weaning. In Experiment 2, treated animals received subcutaneous injections of FGF-2 once daily for one week, postsurgery. Behavioral testing began on postnatal day 60. Brains were later processed for Golgi analysis. We show in Experiment 1, that tactilely stimulating infant rats with perinatal cortical injury stimulates functional recovery and reverses injury-related changes in neuronal morphology in the cerebral cortex. The TS induction of recovery is associated with changes in expression of FGF-2 in both the skin and brain. Direct administration of FGF-2 (Experiment 2) is also effective in facilitating recovery, although not as completely as TS. These results suggest that early behavioral intervention after perinatal cortical injury can stimulate plastic neuronal changes that can underlie functional recovery and that these changes are mediated, in part, through an upregulation of FGF-2.