Induction of Prolonged Electrographic Seizures In Vitro Has a Defined Threshold and Is All or None: Implications for Diagnosis of Status Epilepticus

Summary:  

Summary:   Purpose: To study whether induction of prolonged (>30-min duration) in vitro electrographic seizure discharges resembling status epilepticus (SE) is graded or all-or-none, and to determine the critical factors mediating SE induction.

Methods: Prolonged electrographic seizure discharges were induced in combined hippocampal–entorhinal cortical (HEC) brain slices by electrical stimulation of the Schaeffer collaterals. Discharges were recorded by using field-potential electrodes in the dentate gyrus, CA3, CA1, and entorhinal cortex. Slices were prepared from rats that were (a) 21- to 30-day-old naive, (b) 60- to 120-day old naive, (c) epileptic, and (d) status post a prior traumatic brain injury.

Results: Induction of SE discharges was dependent on the duration, but not amplitude of the preceding stimulus train–induced afterdischarge in HEC slices from 21- to 30-day-old control, brain-injured, and epileptic animals, but not from 60- to 120-day-old animals. In slices from 21- to 30-day-old control animals, once afterdischarges exceeded 4 min in duration, SE was induced in 50% of slices, and after ≥6 min 37 s seizure activity; SE was induced in 95% of slices. A defined SE threshold also was evident in brain-damaged rats, including rats in which an epileptic condition was induced by pilocarpine injection 4–16 weeks before recording, and rats subjected to a fluid percussive head trauma 1–8 weeks before recording. However, in these brain-damaged animals, mean SE threshold was considerably lower (24 and 44 s, respectively). HEC slices from 60- to 120-day-old controls for the brain-injured and epileptic animals did not develop SE even after 20 stimulations, demonstrating the pronounced effect of brain injury and epilepsy on the development of SE in the HEC slice preparation compared with that in age-matched controls.

Conclusions: In vitro, SE discharges have a defined temporal threshold for initiation. Once a seizure exceeds 6–7 min in duration in control animals, and 30–55 s in brain-damaged animals, the probability of SE induction is greatly increased. This demonstrates that brain injury lowers the afterdischarge duration required to produce SE and suggests that brains injured from trauma or SE are more susceptible to develop status epilepticus.