EFFECT OF STATUS EPILEPTICUS ON HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE IMMATURE RAT

Seven-day postnatal rats were subjected to unilateral common carotid a rtery ligation, 3 h after which they were subjected to hypoxia with 8% oxygen at 37 degrees C for 2 h. Thereafter, they received multiple s. c. injection(s) of bicuculline (6 mg/kg) adequate to produce behaviora lly apparent siezures lasting greater than 1 h (status epilepticus). R epeated episodes of status epilepticus at 2, 6, and 12 h of recovery f rom hypoxia-ischemia (HI) produced a mortality rate of 53%. Among the survivors, there was no statistically significant difference in the ex tent of brain damage between convulsing and nonconvulsing HI controls, analyzed at 30 d of age. Histopathologic examination for acute lesion s also indicated no difference in the severity of brain damage between dead and surviving rat pups subjected to status epilepticus, indicati ng that mortality was not related to the severity of prior HI brain da mage. Those immature rats that died during status epilepticus exhibite d lower blood glucose concentrations (1.75 +/- 0.35 mmol/L) compared w ith surviving, convulsing animals (4.25 +/- 0.51 mmol/L; p = 0.016). G lucose supplementation (0.1 mt of 50% glucose) early during status epi lepticus improved survival and significantly prolonged seizure activit y (90 +/- 14 min) compared with nonglucose treated, convulsing litterm ates (47 +/- 10 min; p = 0.02). Glucose supplementation did not increa se the extent of brain damage despite improved survival and increased duration of seizure activity. The findings indicate that even repetiti ve episodes of status epilepticus in immature rats previously subjecte d to cerebral HI do not accentuate brain damage despite a substantial mortality. Hypoglycemia contributes to death arising from status epile pticus, and both survival and seizures can be prolonged by glucose sup plementation without risk of increasing the severity of any existing b rain damage.