GM1 Ganglioside treatment after global ischemia protects changes in membrane fatty acids and properties of Na+, K+‐ATPase and Mg2+‐ATPase

Abstract

An examination was made of the effects of ganglioside GM1 (i.m.) on the losses of membrane fatty acids (palmitic, stearic, oleic, linoleic, and arachidonic), the plasma membrane enzyme Na+, K+-ATPase, and the mitochondrial membrane enzyme Mg2+-ATPase, associated with global ischemia 24 hr after permanent unilateral occlusion of the carotid artery in Mongolian gerbils. While there was a significant loss of fatty acids in saline controls, no loss was detected in membranes from GM1-injected gerbils. Rather, we found an increase in membrane fatty acid content, indicative of altered turnover. A 38% loss of Na+, K+-ATPase and a 36% loss of mitochondrial Mg2+-ATPase observed in membranes from saline controls was reduced in membranes from GM1-injected animals to losses of 15% and 8% respectively. These effects are further described by analyses of enzyme kinetics (apparent Vmax and apparent Km). After 1 week of storage, the activities of both membrane ATPases from saline controls decreased substantially more than from GM1-injected animals, suggesting that the GM1 membranes were better "preserved." Since there was a minimal loss in protein content after 24 hr of ischemia, these results indicate that systemically injected GM1 may protect structure and function of plama membranes during the acute phases of ischemic injury.

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

“…These GM1 effects were observed as early as 24 hr after the ischemic insult and occur in both primary infarct and peri-ischemic cortical tissue. We have previously reported that GM1 ganglioside treatment reduces tissue plasma membrane damage as evidenced by analyses of plasma membrane Na, K-ATPases in inschemic tissue from animals with global ischemia (Karpiak et al, 1987a,b;Mahadik et al, 1989) as well as focal cortical ischemia (Bharucha et al, 1991). 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).…”

“…Recent clinical studies support the efficacy of ganglioside treatment for CNS ischemia (Argentino et al, 1989). The ability of GM1 ganglioside treatment to reduce CNS injury has been detailed by many research reports (reviewed by Karpiak et al, 1990;Mahadik et al, 1989). The mechanism(s) by which these glycosphingolipids are neuroprotective agents remain( s) unclear.…”

“…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).…”

Oxidative damage and cerebral aging

“…Ganglioside GM!, a membrane-stabilizing agent effective within the CNS, may also mitigate some components of oxidative damage to neural tissue. This ganglioside has been reported protective against ischemia (Mahadik et al, 1989), edema (Koga et al, 1990, Skaper et al, 1989, and direct oxidative activity (Bondy and McKee, 1990). The therapeutic application of macromolecular proteins as a means of reducing ROS production is obviously somewhat limited.…”

Avanços no uso de células-tronco em ortopedia

“…Methylprednisolone administered within the first eight hours after the trauma was the first agent to produce a significant improvement in the recovery from spinal cord trauma in human beings (4,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) . Other drugs, like tirilazad (47)(48)(49) and GM-1 (50)(51)(52)(53)(54)(55)(56)(57) have presented promising preliminary results. These advances may provide a great improvement in the quality of life of patients with spinal cord injuries, if they are brought into clinical practice.…”