FGF-2-induced functional improvement from neonatal motor cortex injury via corticospinal projections

Abstract

The administration of basic fibroblast growth factor (FGF-2) to rats with postnatal 10 (P10) motor cortex (MCx) lesions results in functional improvements accompanied with filling of the previously lesioned area with tissue. In the present experiment, we tested the prediction that FGF-2 induces functional recovery by promoting meaningful reconnection of neurons from the filled region to the periphery. Rats received bilateral MCx lesions on P10 and subcutaneous injections of either vehicle or FGF-2 for 7 days beginning on P11. In adulthood, we evaluated the physiology and anatomy of corticospinal projections using intracortical microstimulation together with recordings of evoked electromyographic (EMG) activity in wrist extensors, and anterogradely tracing projecting axons using biotin dextran amine. We found that activity could be induced in the wrist extensors following stimulation of the filled region with onset delays comparable to undamaged corticospinal tract fibers in 5 out of 7 lesioned, FGF-2 treated rats. Furthermore, in the rats in which EMG activity could be elicited, long descending axons were labeled with projections into the spinal cord comparable to corticospinal tracts from undamaged motor cortex. Our results demonstrate that FGF-2 treatment restores the connectivity of the filled region in neonatal rats. This provides a possible mechanism for FGF-2-induced functional recovery.