Abstracts

The testing of the effectiveness of novel drugs and other therapeutic modalities using reproducible focal animals epilepsy models is of major importance. Few models of reproducible acute focal neocortical seizures have been described. Penicillin (topical application) was previously used in cats, rabbits, and sheep to induce acute seizures. We developed a model of acute induction of long lasting focal motor seizures using small focal intracortical injections of penicillin in the motor cortex of the rats. Five adult male Sprague Dawley rats (Charles River, MA, USA) weighing 260-300 g were used according to a protocol approved by the CCF ARC. Under ketamine anesthesia (0.1ml/100 g i.p.), a stainless-steel canula (Plastic One,VA, USA) with an inner needle (0.3mm in diameter) was stereotaxically inserted into the right motor cortex (A= 3mm, L = 2mm, D = -1mm). For EEG recordings, the canula was also used as a recording electrode and a screw electrode was implanted 1mm lateral. Four additional epidural screw electrodes were implanted (bi-parietal and bi-frontal areas, the right frontal electrode used as reference). Seven days after surgery, under light ketamine general anesthesia (0.05ml/100 g), penicillin (2,250 units in 7.5[mu]l) was injected over 15 minutes using a Hamilton syringe. Fifteen video EEG recording sessions (total of 3 injections/rat every 3 days) were performed using the Vangard digital EEG system (Lamont Inc, USA). All the rats exhibited focal seizures that typically started 5 to 10 min after the start of penicillin injection and lasted for 2 to 5 hours. We identified 4 consecutive electro-clinical patterns: I consisted of irregular focal spiking ([lt]800 [mu]V in amplitude, 5 to 20 min in duration) with no behavior manifestation; II consisted of burst of rhythmic focal spiking (800 to 1200 [mu]V in amplitude, 3 to 20 mn in duration) associated with controlateral forelimb clonic movements; III consisted of continuous rhythmic focal or lateralized (ipsilateral parietal area) spikes or polyspikes (1200 to 3000 [mu]V in amplitude, 1 to 4 hours in duration); IV consisted of secondary generalization of EEG electrical patterns (occurred once in one rat). The intracortical injection of penicillin leads to reproducible and stereotypical electro-clinical patterns in the rat. This model may be ideal for the testing of novel therapeutics or surgical intervention designed for the control of focal neocortical seizures. (Supported by a grant from the French league against Epilepsy, the French society for Neurosurgery and the city of Vias, France. IN was supported by R21 NS42354 and K08 NS02046 grants from the national institute of Healths (NIND))