Experimental studies suggest that the delivery of antiepileptic agents into the seizure focus might be of potential utility for the treatment of focal-onset epilepsies. Botulinum neurotoxin E (BoNT/E) causes a prolonged inhibition of neurotransmitter release after its specific cleavage of the synaptic protein synaptosomal-associated protein of 25 kDa (SNAP-25). Here, we show that BoNT/E injected into the rat hippocampus inhibits glutamate release and blocks spike activity of pyramidal neurons. BoNT/E effects persist for at least 3 weeks, as determined by immunodetection of cleaved SNAP-25 and loss of intact SNAP-25. The delivery of BoNT/E to the rat hippocampus dramatically reduces both focal and generalized kainic acid-induced seizures as documented by behavioral and electrographic analysis. BoNT/E treatment also prevents neuronal loss and long-term cognitive deficits associated with kainic acid seizures. Moreover, BoNT/E-injected rats require 50% more electrical stimulations to reach stage 5 of kindling, thus indicating a delayed epileptogenesis. We conclude that BoNT/E delivery to the hippocampus is both antiictal and antiepileptogenic in experimental models of epilepsy.
Antiepileptic effects of botulinum neurotoxin E / L. Costantin, Y. Bozzi, C. Richichi, A. Viegi, F. Antonucci, M. Funicello, M. Gobbi, T. Mennini, O. Rossetto, C. Montecucco, L. Maffei, A. Vezzani, M. Caleo. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - 25:8(2005), pp. 1943-1951.
Titolo: | Antiepileptic effects of botulinum neurotoxin E | |
Autori: | ||
Parole Chiave: | neurotransmitter release; kainic acid; seizures; Morris water maze; neuronal death; hippocampal kindling | |
Settore Scientifico Disciplinare: | Settore BIO/14 - Farmacologia | |
Data di pubblicazione: | 2005 | |
Rivista: | ||
Tipologia: | Article (author) | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1523/JNEUROSCI.4402-04.2005 | |
Appare nelle tipologie: | 01 - Articolo su periodico |
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