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Neuroscience. 2013 Nov 12;252:253-61. doi: 10.1016/j.neuroscience.2013.07.050. Epub 2013 Jul 29.

Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat.

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1
Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, USA.

Abstract

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target SNAP-25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1,000 unit) by convection-enhanced delivery caused a reduction in myoclonic twitch and clonic seizure thresholds in response to intravenous PTZ beginning about 6 days after the infusion. Handling-evoked and spontaneous convulsive seizures were observed in many BoNT/B-treated animals but not in vehicle-treated controls. Spontaneous electrographic seizure discharges were recorded in the dentate gyrus of animals that received local BoNT/B infusion. In addition, there was an increased frequency of interictal epileptiform spikes and sharp waves at the same recording site. BoNT/B-treated animals also exhibited tactile hyperresponsivity in comparison with vehicle-treated controls. This is the first demonstration that BoNT/B causes a delayed proconvulsant action when infused into the hippocampus. Local infusion of BoNT/B could be useful as a focal epilepsy model.

KEYWORDS:

ANOVA; BoNT; CED; EEG; PEEK; PTZ; SNAP-25; U; VAMP2; analysis of variance; botulinum neurotoxin; convection-enhanced delivery; electroencephalogram; epilepsy; hippocampus; pentylenetetrazol; polyaryletheretherketone; seizure; synaptosomal-associated protein of 25 kDa; unit; vesicle-associated membrane protein 2

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