Effect of the ganglioside GM1, on cerebral metabolism, microcirculation, recovery kinetics of ECoG and histology, during the recovery period following focal ischemia in cats.

Abstract

SUMMARY The effect of the ganglioside GM1 on the recovery of local cerebral glucose metabolism QCMRgl), recovery kinetics of cerebrocortical electrical activity, cerebral blood flow and redox state as well as histological changes following focal ischemia has been studied in the cat. Ischemia was produced by occlusion of the left middle cerebral artery (MCA), and GM1 (30 mg/kg) was injected intravenously at 30 min after the MCA occluson or at the time of release of the occlusion, at 120 min. Another group of animals were subjected to the same ischemic insult, but without GM1 treatment, and sham-operated treated and not treated cats were also studied. The animals of both GM1-treated and non-treated stroke groups were classified into 2 groups (severe and moderate) depending on the depression of electrocortical activity in the ischemic hemisphere at 30 min of the ischemia. There was a significant increase in local cerebral blood flow in the ischemic area in the treated animals. Additionally there was a significant treatment effect on the left peripheral MCA territory for ICMRgl in the 30 min treated moderate group, (p < .05). This group of animals showed decreased ICMRgl accompanied by less severe histological damage suggesting that GM1 may produce metabolic depression so as to maintain a normal flow-metabolism couple and prevent ischemic structural damage. The possible mechanism of metabolic depression induced by GM1 is briefly discussed.

Effect of GM1 ganglioside after focal cerebral ischemia in halothane-anesthetized cats.

“…[K + ] e indicates an absence of "complete membrane failure," which is usually accompanied by excessive K + leakage to the extracellular space. 22 In previous experiments we studied the effect of GM1 on glucose metabolism, 8 and a decrease in lCMRgl was found in the P MCA of the moderate treated cats, with a significant morphologic improvement, perhaps due to a reduction of glycolytic activity in the periphery of the focal ischemic zone, in this region. During focal ischemia, a region of increased glucose utilization frequently surrounds the central ischemic core, 23 due most likely to the presence of anaerobic glycolysis.…”

“…24 - 23 Anaerobic glycolysis persists even during recirculation, although to a lesser degree. 26 The decreased glycolysis seen in the GM1-treated cats with barbiturate anesthesia 8 probably leads to less lactic acid accumulation, diminishing the acidotic pH shift that has been indicated as one of the significant detrimental factors in ischemic cell damage. 2728 The overall metabolic activity in the shamoperated group in this light halothane/N 2 Oanesthetized series was approximately 30% higher than that in our previous study in which pentobarbital was used as the anesthetic.…”

“…8 Histologic damage was also attenuated by GM1, suggesting that this natural membrane constituent may have a protective effect against ischemic brain damage. However, since in the above-mentioned study ICMRgl values even in the sham-operated group were low due to barbiturate anesthesia, it seemed reasonable to measure ICMRgl using halothane/N 2 O anesthesia.…”

“…In addition to the variables measured in our previous study 8 (electrocortical activity [ECoG], cerebrocortical blood flow (CBF), nicotinamide adenine dinucleotide [NAD/NADH] redox state changes), in the present study we also measured [K + ] e , a sensitive indicator of neuronal membrane damage, in the central MCA territory (C MCA) of the brain cortex of cats during 120 minutes of focal cerebral ischemia as well as during the first 240 minutes of reperfusion. We also studied the changes of lCMRgl at the end of recirculation.…”

Influence of monosialoganglioside inner ester on neurologic recovery after global cerebral ischemia in monkeys.

“…In cats with transitory focal ischemia, a single dose of GM 1 increases CBF in the ischemic area, and GM 1 depresses local CMRGlu in the peripheral middle cerebral artery territory, in which the morphologic damage is less severe in treated cats. 8 Thus, we hypothesize that the improved neurologic recovery we observed may result from the ganglioside's ability to maintain structural integrity and/or blood flow-metabolism coupling adapted to the needs of the brain. Which of these two possibilities plays the predominant role is currently under investigation.…”