Efficacy of Lacosamide and Rufinamide as Adjuncts to Midazolam-Ketamine Treatment Against Cholinergic-Induced Status Epilepticus in Rats.

Benzodiazepine pharmacoresistance develops when treatment of status epilepticus (SE) is delayed. This response may result from gamma-aminobutyric acid A receptors (GABAR) internalization that follows prolonged SE; this receptor trafficking results in fewer GABAR in the synapse to restore inhibition. Increase in synaptic N-methyl-D-aspartate receptors (NMDAR) also occurs in rodent models of SE.

Evaluation of Midazolam-Ketamine-Allopregnanolone Combination Therapy against Cholinergic-Induced Status Epilepticus in Rats.

Status epilepticus (SE) is a life-threatening development of self-sustaining seizures that becomes resistant to benzodiazepines when treatment is delayed. Benzodiazepine pharmacoresistance is thought in part to result from internalization of synaptic GABA receptors, which are the main target of the drug. The naturally occurring neurosteroid allopregnanolone is a therapy of interest against SE for its ability to modulate all isoforms of GABA receptors.

Fifty years of research on status epilepticus: Seizures use hippocampal memory circuits to generate status epilepticus and disrupt brain development.

This is a review of my laboratory's interest in status epilepticus (SE), which spanned five decades. It started with a study of the role of brain mRNAs in memory, and with the use of electroconvulsive seizures to disrupt recently acquired memories. This led to biochemical studies of brain metabolism during seizures, and to the serendipitous development of the first model of self-sustaining SE.