Toward a unified theory of ganglioside-mediated functional restoration after brain injury: lesion size, not lesion site, is the primary factor determining efficacy.

Pharmacological intervention is receiving increasing attention as a strategy to promote recovery of function after central nervous system injury. In this review we describe numerous studies indicating that gangliosides have been particularly successful in promoting CNS repair across a wide spectrum of brain areas and behavioral paradigms. A detailed comparison of these studies reveals common features among those studies where ganglioside treatment was found to be beneficial and those where no effect was observed. Specifically, treatment efficacy was only seen in those paradigms where recovery occurs naturally after the injury and not in those where either the behavioral deficit was too small ("ceiling effect") or too extensive for spontaneous recovery to occur ("floor effect"). Thus, ganglioside treatment is only effective in cases of moderate (partial) injury and/or when behavioral recovery occurs naturally. The effect is independent of lesion site or lesion type. On the basis of these observations, we propose a model based on the relationships of neural aggregates (cell groups) which have either a primary or modulatory role in brain function. Our model may provide a heuristic basis for future research efforts aimed at elucidating the mechanism(s) whereby gangliosides enhance brain repair.