Monosialoganglioside GM1 treatment after a hypoxic-ischemic episode reduces the vulnerability of the fetal sheep brain to subsequent injuries.

OBJECTIVE: A transient hypoxic-ischemic episode can markedly sensitize regions of the fetal brain, particularly the striatum, to further insults occurring in close succession. The purpose of this study was to determine whether ganglioside GM1 given to the fetus after a hypoxic-ischemic episode can counteract this sensitization and protect against subsequent insults. STUDY
DESIGN: Chronically instrumented near-term fetal sheep (119 to 133 days) were subjected to three 10-minute episodes of reversible cerebral ischemia at 1-hour intervals. Six were given 30 mg/kg ganglioside GM1 through the umbilical vein, commencing immediately after the release of the occluder, over the next 2 hours, followed by a continuous infusion of 30 mg/kg/day over 60 hours after ischemia; these were compared with seven vehicle-treated controls. The time course of electrocorticographic activity and cytotoxic edema within the parasagittal cortex were determined with real-time spectral analysis and continuous impedance measurements, respectively. The degree and distribution of neuronal death was assessed histologically 72 hours later.
RESULTS: Ganglioside GM1 improved recovery of primary edema and markedly reduced histologic damage (p < 0.001), particularly in the striatum, hippocampus, and cortex. At 72 hours after ischemia electrocorticographic activity had returned to normal in the ganglioside GM1-treated group but was still depressed (p < 0.001) in the control group.
CONCLUSION: These results showed that ganglioside GM1 treatment initiated immediately after a transient hypoxic-ischemic episode stabilized membrane function and markedly improved neuronal outcome after subsequent insults, suggesting its potential therapeutic value in acute situations of repeated hypoxia-ischemia in the perinatal period.