Gangliosides (GM1 and AGF2) reduce mortality due to ischemia: protection of membrane function.

Abstract

As evidenced by their ability to reduce cerebral edema, exogenous ganglioside administration exerts acute effects on CNS injury processes. We report here that ganglioside (GMI or AGF2) treatment results in a 52% decrease in mortality 48 hours after the Induction of ischemia in gerbils by permanent unilateral ligation of the common carotid artery. By comparing the occluded vs. nonoccluded sides of the brain (cortex and hippocampus) we found a significant loss of membrane Na, K-ATPase activity due to ischemia in control «niipals, but no such differences were found between the hemispheres of ganglioside-treated gerbils. We hypothesize that gangliosides may be "protecting" membrane function as indicated by these ATPase analyses, reducing local CNS damage at the time of injury (i.e., reduced cell loss, fiber degeneration, membrane failure). By acutely limiting the extent of CNS tissue damage, conditions may be optimized for any subsequent CNS regrowth and functional recovery.

Inhibition of protein kinase C induces differentiation in Neuro-2a cells.

“…Based on their neural regenerative effect, gangliosides have been used successfully in animal models for the treatment of certain neurological disorders, such as diabetic neuropathy (18)(19)(20), and for acceleration of functional recovery after central nervous system damage (21)(22)(23) (24,25) and is capable of spontaneously differentiating or maturing to a benign ganglioneuroma (26 therefore agents that modify its activity might be of importance in the treatment of certain neuropathies and tumors, especially neuroblastomas.…”

Temporal changes in edema, Na+, K+, and Ca++ in focal cortical stroke: GM1 ganglioside reduces ischemic injury

“…These acute effects may underlie the multiple reports of longterm improved functional recovery in animals with CNS damage that were treated with GMl ganglioside Karpiak et al, 1989). Since the focus of ischemic injury is the CNS cell plasma membrane, we have hypothesized that exogenous gangliosides are likely to protect or maintain the "physiological potential" of the injured CNS cell to defend against, or recover from, acute injury processes (e.g., ionic changes, edema, free radical formation) by preserving membrane structure/ function (Karpiak et al, 1983(Karpiak et al, , 1984(Karpiak et al, , 1987a(Karpiak et al, ,b, 1990Li et al, 1986;Mahadik et al, 1989;Mazzari et al, 1990).…”

Mechanistic Basis for the Development of Anti-Ischemic Drugs

“…N a \ K* and Mg:+ ATPase...). In a model of unilateral carotid ligature in the gerbil, GM1 (or AG 12) reduced by 52% the mortality at 48 h and reduced the size of the infarction [68], These results have been controlled in man. The role of scavengers trapping free radicals remains controversial [62,[69][70][71], New molecules have appeared in the literature, such as MCI 186 [72], Finally, the protective role of RX 77368. a thyrotropin-releasing hormone analog, through possible vascular action is mentioned [73].…”