RT Journal Article
SR Electronic
T1 Antiepileptic Effects of Botulinum Neurotoxin E
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1943
OP 1951
DO 10.1523/JNEUROSCI.4402-04.2005
VO 25
IS 8
A1 Laura Costantin
A1 Yuri Bozzi
A1 Cristina Richichi
A1 Alessandro Viegi
A1 Flavia Antonucci
A1 Marcella Funicello
A1 Marco Gobbi
A1 Tiziana Mennini
A1 Ornella Rossetto
A1 Cesare Montecucco
A1 Lamberto Maffei
A1 Annamaria Vezzani
A1 Matteo Caleo
YR 2005
UL http://www.jneurosci.org/content/25/8/1943.abstract
AB 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.