1. ¹Departments of Neuroscience and Neurosurgery, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA
2. ²Department of Neurology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA
3. ³Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA

Correspondence: Nicholas M Boulis, Center for Neurological Restoration, Departments of Neurosciences and Neurosurgery, Lerner Research Institute: NB2-126, Cleveland Clinic Lerner College of Medicine, 9500 Euclid Ave., Cleveland, Ohio 44195, USA. E-mail: boulisn@ccf.org

Received 11 July 2006; Accepted 5 October 2006; Published online 9 January 2007.

Abstract

Restraining excitatory neurotransmission within a seizure focus provides a nondestructive treatment strategy for intractable neocortical epilepsy. Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a critical vesicle-docking protein, synaptobrevin, without directly altering neuronal health. This study tests the treatment efficacy of adenoviral vector delivered LC (AdLC) on a model of seizures in rats induced by motor cortex penicillin (PCN) injection. LC expression significantly reduced electroencephalogram (EEG) frequency, amplitude, duration, and latency compared to control groups injected with either an adenoviral vector bearing green fluorescent protein (AdGFP) or phosphate buffered solution (PBS). Correspondingly, LC gene expression improved behavioral manifestations including seizure severity and latency. There was no statistical difference in motor function before and after vector administration between treatment and control groups. Histological analysis revealed spatially discrete LC expression with corresponding synaptobrevin depletion in the cortex surrounding the injection site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG and behavioral manifestations of PCN-induced focal neocortical seizures through synaptobrevin depletion.