Abstracts

Direct injection of a drug onto a seizure focus might improve the therapeutic ratio of the treatment. We previously have shown that focal drug injection can interrupt ongoing spiking and seizures. Such treatments might be even more useful if given before seizures. We describe an[italic] in vivo[/italic] assay methodology for screening potential anti-epileptic medications by prophylactic injection onto a seizure focus.
The left hippocampi of 15 rats were implanted with an injection cannula and bipolar recording electrodes, and five bone screws were used to record neocortical activity. The experimental paradigm consisted of prophyactic treatment with control solution or diazepam via the hippocampal cannula, followed five minutes later by an infusion of 0.01 cc of 0.1 mM bicuculline methiodide (BMI) through the same cannula. The control group received 0.02 cc of dimethyl sulfoxide (DMSO), and treatment groups received 0.02 cc of 1.0, 10, 100 or 400 mM diazepam (DZP) dissolved in DMSO. In random order, each animal received one of each of the five treatments for five days in a row. Following each treatment, we recorded video-EEG for 15 minutes. A board-licensed electroencephalographer, unaware of treatment group, reviewed the records digitally and scored them for the outcomes shown in Table 1. Comparison was performed by a linear regression model using SPSS.
Table 1 summarizes the mean and standard error for each group, with respect to the number of spikes, total number of seizures, latency to the first spike, and latency to the first seizure.[table1]
This study establishes a methodology to evaluate potential anti-seizure medications as locally infused therapy in advance of spikes and seizures. The study also demonstrates an effective dose-response curve for intracranial injection of DZP to prevent epileptiform events induced by BMI.
[Supported by: The National Epi-Fellows Foundation, The CURE Foundation, the Maslah Saul Chair, and the James and Carrie Anderson Epilepsy Research Fund.]