ee-581 and Epilepsy

In vivo observation of the ictal events are thought to help understanding the etiology and pathology in both epilepsy and migraine. While simultaneous recording of EEG and fMRI is actively conducted for the former, in some cases, epileptogenic activity is undetectable by EEG. Attempts to detect such abnormal brain activity by using fMRI are underway. Analysis methods for resting-state fMRI can be applicable for such purposes. For migraine, fMRI is also highly valuable in detecting series of ictal events. However, since the disease is suspected to involve abnormal neuro-vascular coupling, it is not always straightforward how to interpret the observation by vascular-dependent methods. Therefore development of non-vascular methods is critical for future advances.

Topics: Azides; Brain; Epilepsy; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Migraine Disorders; Octreotide

In vivo and in vitro evidence from animals suggesting that gap junctions (GJs) play a role in the spreading of epileptiform activity. We have examined the influence of the gap junction opener trimethylamine (TMA) and the connexin 36 (Cx36) gap junctional blocker, quinine, on epileptiform activity induced by 4-aminopyridine (4-AP) in the rat entorhinal cortex (EC) and the CA1 hippocampal region. A cannula and surface electrodes were implanted into the brain to administer drugs and to monitor electrical activity. Injection of 4-AP (10 nmol) produced epileptiform discharge trains of high amplitude and frequency associated with seizure behavior rated between 0 and 3 in the Racine scale. In the presence of TMA (500 nmol), 4-AP produced distinct epileptiform patterns with continuous, long epileptiform discharges of high amplitude and frequency associated with seizure behavior of 0, 1, 3 and 5 during the first 30 min post-drug administration that diminished after 90 min. Quinine injection (35 pmol) into the EC of seizing animals decreased the amplitude and frequency of the discharge trains in the EC and CA1 regions, which were completely blocked after 34 min. Indeed, the seizure behavior of the animals was completely blocked in five of the six rats 53.2s after quinine administration. We suggest that the intensity of the proepileptic effect of TMA on epileptiform activity depends on the time and route of drug administration, and that neural Cx36-dependent GJs are important structures in the generation of epileptiform activity, as well as in the seizure behavior induced by 4-AP.

Topics: 4-Aminopyridine; Animals; Azides; Behavior, Animal; CA1 Region, Hippocampal; Entorhinal Cortex; Epilepsy; Gap Junctions; Male; Methylamines; Octreotide; Potassium Channel Blockers; Quinine; Rats; Rats, Wistar; Wakefulness