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

Cortical focal ischemia in the rat was induced by middle cerebral artery occlusion (MCAo) together with permanent occlusion of the ipsilateral common carotid artery (CCAo) and a temporary (1 hr) occlusion of the contralateral CCA. By using a defined cortical tissue sampling procedure at 3, 6, 24, 72, 96, and 120 hr after the MCAo + CCAo, patterns of edema and ion (Na⁺, K⁺, and Ca⁺⁺) changes in a primary and three peri‐ischemic cortical areas are described. Ionic imbalances and edema formation have distinct patterns, are time dependent, and are different when comparing primary and peri‐ischemic areas. Calcium increases to “neurotoxic” levels appear temporally independent of edema formation, reaching magnitudes 20 times greater than basal levels in the pri‐mary infarct area. Na⁺ increases correlate with increases in water, while K⁺ losses do not appear to be directly related to edema formation or Na⁺ and Ca⁺⁺ increases. K⁺ losses are only significant in the primary infarct area. Rats treated with GM1 ganglioside (10 mg/kg, i.m.) daily showed significant reductions in edema, Na ⁺ and Ca ⁺⁺ increases. These ganglioside effects were evident as early as 24 hr after the ischemic injury. Ca⁺⁺ increases, which was maximal at 72 hr after the ischemic injury, was reduced by greater than 50% in GM1‐treated animals. The mechanism by which GM1 is an effective neuroprotective agent may be evidenced by its effects on Ca⁺⁺ influx/efflux processes in injury.