Long-lasting attenuation of amygdala-kindled seizures after convection-enhanced delivery of botulinum neurotoxins A and B into the amygdala in rats

Maciej Gasior, Rebecca Tang, Michael A Rogawski

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convectionenhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64- day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally,maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.

Original languageEnglish (US)
Pages (from-to)528-534
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume346
Issue number3
DOIs
StatePublished - Sep 2013

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Convection
Type A Botulinum Toxins
Neurotoxins
Amygdala
Synaptic Transmission
Seizures
Brain
Brain Diseases
Body Temperature
Cholinergic Agents
Epilepsy
Electrodes
Protein Isoforms
Observation
Weights and Measures
Muscles
rimabotulinumtoxinB

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

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title = "Long-lasting attenuation of amygdala-kindled seizures after convection-enhanced delivery of botulinum neurotoxins A and B into the amygdala in rats",
abstract = "Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convectionenhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64- day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally,maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.",
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