Skaper S D, Leon A
FIDIA Research Laboratories, Abano Terme, Italy.
J Neurotrauma. 1992 May;9 Suppl 2:S507-16.
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.
神经节苷脂在神经系统，尤其是大脑的生理活动中发挥着重要作用。神经节苷脂的组成变化不仅发生在哺乳动物大脑的发育过程中，也出现在衰老过程以及一些神经病理情况下。神经节苷脂可能会调节大脑改变其对周围环境信号反应的能力。例如，培养的神经元对外源性神经节苷脂的反应具有分化特征性变化；这些唾液酸糖鞘脂还会增强神经元对神经营养因子的反应。更多的体外研究表明，像GM1这样的单唾液酸神经节苷脂通过限制受体过度刺激的下游后果来预防兴奋性氨基酸相关的神经毒性。全身给予GM1可有效减少急性神经细胞损伤，并促进成年哺乳动物中枢神经系统遭受各种类型损伤后的中长期功能恢复。GM1在急性损伤期的保护作用至少部分可能源于兴奋性毒性的减轻，而长期功能恢复可能反映了GM1对神经营养因子的增强作用。近期在急性人类中风、蛛网膜下腔出血和脊髓损伤方面的积极临床研究结果，为GM1的潜在治疗效果提供了支持。
