Status Epilepticus in Immature Rats

Abstract

The role of glucose metabolism in alleviating the complications of status epilepticus (SE) was investigated in developing rats. Pretreatment with glucose reduced mortality from SE by 90% in rats under 1 week of age, 80% in 10-day-old rats, 50% in 15- to 20-day-olds, and not at all in adults. In 4-day-old animals, brain DNA synthesis during seizures, and in survivors, brain weight, DNA, RNA, protein, and cholesterol contents at 7 days of age were reduced less in glucose-treated than in saline-treated littermates. In the saline group, seizures caused a progressive fall in brain glucose level but no fall in blood glucose level, suggesting that glucose transport from blood to brain could not keep pace with glycolytic demands. In glucose-treated rats, blood and brain glucose concentrations remained elevated throughout the convulsive period. There was no reduction of brain adenosine triphosphate levels in either group. Thus, the protection by glucose appears to be related to its roles as a carbon source rather than an energy source. It is concluded that in immature animals, depletion of brain glucose can occur in the absence of hypoglycemia, and may be an important and potentially treatable complication of status epilepticus.

Prolonged Neonatal Seizures Exacerbate Hypoxic-Ischemic Brain Damage: Correlation with Cerebral Energy Metabolism and Excitatory Amino Acid Release

“…The combination of metabolic alterations that occurs with hypoxicischemic injury followed by prolonged seizures results in the enhanced damage displayed in the hippocampus. In the immature brain, normally resistant to the cell death following KA-induced seizures [Carmant et al, 1995;Wasterlain and Duffy, 1976;Wirrell et al, 2001;Fernandes et al, 1999], a prolonged depletion of high-energy phosphates is required as a prerequisite to the release of high enough concentrations of glutamate during seizures to enhance neuronal damage.…”

A selective and critical review of neuropsychological deficits and the frontal lobes

“…Dodrill (1981) reviewed reports of patients with refractory seizures whose neuropsychological functions deteriorated over time. He noted that Harris (1972) and Wasterlain and Duffy (1976) demonstrated neuronal degeneration associated with repeated seizures in animals, and that seizures also have an inhibitory effect on brain protein synthesis, on brain growth, and eventually on behavioral development. Citing Arieff and Yacorzynski (1942), De Haas and Magnus (1958), and Lennox and Lennox (1960), Dodrill commented that "with these studies as a background, it is not surprising that several investigators do implicate a gradual deterioration of abilities" in patients who experience epileptic attacks repeatedly.…”

Brain Energy Metabolism During Experimental Neonatal Seizures

“…Studies in newborn dogs showed reductions of brain phosphocreatine and prolonged elevations of inorganic phosphate and lactate after seizures induced by electroshock [55] or bicuculline [32], suggesting enhanced glycolysis. In a previous study [52], we found that in 4-day-old rats, an age roughly comparable to a human premature or term neonate, brain ATP concentrations measured 1 min after the end of exposure to the convulsant flurothyl did not show the progressive depletion of energy reserves with repeated seizures during the course of status epilepticus which has been described in adults. These results, however, did not rule out a transient decline during seizures.…”

“…Our previous investigations [52] showed no decline in post-ictal ATP during the course of status epilepticus in 4-day-old rats, but the animals were frozen during the post-ictal period, 1 min after removal of the convulsant. ATP concentrations were not measured during the seizures in that study.…”