Monosialogangliosides, neuroprotection, and neuronal repair processes

Gangliosides play important roles in the physiologic operations of the nervous system, in particular that of the brain. Changes in ganglioside composition occur in the mammalian brain not only during development, but also in aging and in several neuropathologic situations. Gangliosides may modulate the ability of the brain to modify its response to signals from the surrounding environment. For example, cultured neurons respond to exogenous gangliosides with changes characteristic of differentiation; these sialoglycosphingolipids also amplify the response of neurons to neurotrophic factors. Additional in vitro studies have shown that monosialogangliosides like GM1 protect against excitatory amino acid-related neurotoxicity by limiting the downstream consequences of receptor overstimulation. Systemic administration of GM1 is efficacious in reducing acute nerve cell damage and in facilitating medium- and long-term functional recovery following various types of injury to the adult mammalian central nervous system. The GM1 protective effects in the acute injury phase likely result, at least in part, from attenuation of excitotoxicity, while long-term functional recovery may reflect GM1 potentiation of neurotrophic factors. The potential therapeutic efficacy of GM1 is encouraged by recent positive clinical findings in acute human stroke, subarachnoid hemorrhage, and spinal cord injury.