MONOSIALOGANGLIOSIDE (GM1) RESTORES MEMBRANE FATTY-ACID LEVELS IN ISCHEMIC TISSUE AFTER CORTICAL FOCAL ISCHEMIA IN RAT

Using a consistent, reproducible and reliable cortical focal ischemia in rat (permanent unilateral occlusion of the left middle cerebral art ery & the ipsilateral common carotid artery MCAo + CCAo! with a 1 h t emporary occlusion of the contralateral CCA), the levels of four major membrane fatty acids (palmitic, C16 : 0 : stearic, C18 : 0; Oleic, C1 8 : 1 and arachidonic, C20 : 4) were analyzed at 3, 36 and 72 h, and 2 and 4 wk following ischemia to determine the critical point of irreve rsibility of the cellular plasma membrane disorganization in primary i schemic (Area 1, parietal cortex) and peri-ischemic (Area 2, tempero-o ccipital cortex) areas. The cortical focal ischemia resulted in time d ependent differential loss in four of these major membrane fatty acids . The quantitative differences among primary and peri-ischemic areas r eflected the different degree of ischemic injury inflicted to these re gions. Acute treatment with ganglioside GM1 protected the further loss es of all of these fatty acids and differentially restored their level s in these various injury sites over periods of time. The changes in l evels of these membrane fatty acids indicate that the primary ischemic area suffers an irreversible injury and peri-ischemic area suffers re versible injury. After acute treatment (<2 h) with ganglioside GM1, a partial recovery was observed in primary ischemic area and complete re covery was observed in peri-ischemic areas. These studies support the hypothesis that, ischemia leads to a irreversible plasma membrane diso rganization which underlies the eventual cell death, and protection an d restoration of these membrane changes by drugs, such as ganglioside GM1 leads to neuroprotection against ischemic injury.