Action of botulinum neurotoxins in the central nervous system: Antiepileptic effects

Bozzi, Yuri; Costantin, Laura; Antonucci, Flavia; Caleo, Matteo

doi:10.1007/bf03033939

Cited by 42 publications

(23 citation statements)

References 52 publications

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“…The action of BoNT/E is completely reversible, because the protease is inactivated with time and intact SNAP-25 is wholly replenished (Keller et al, 1999;Costantin et al, 2005). Thus, BoNT/E combines a potent and long-lasting action with full reversibility at the cellular level (Bozzi et al, 2006). These features make BoNT/E an ideal tool to address the role of synaptic activity in the brain.…”

Section: Discussionmentioning

confidence: 99%

Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

Caleo¹,

Restani²,

Gianfranceschi³

et al. 2007

J. Neurosci.

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Neural circuits in the cerebral cortex are shaped by experience during "critical periods" early in life. For example, visual cortex is immature at the time of eye opening and gradually develops its functional properties during a sensitive period. Very few reports have addressed the role of intrinsic neural activity in cortical maturation. Here we have exploited the bacterial enzyme botulinum neurotoxin E (BoNT/E) to produce a unilateral, reversible blockade of neural activity in rat visual cortex during the sensitive period. BoNT/E is a highly selective protease that interferes with transmitter release via cleavage of the synaptic protein SNAP-25 (synaptosomal-associated protein of 25 kDa). Unilateral, intracortical injections of BoNT/E were made at the time of eye opening and resulted in the silencing of the treated, but not contralateral, hemisphere for a period of 2 weeks. We found that visual acuity was permanently reduced in the blocked hemisphere, and the critical period for ocular dominance plasticity persisted into adulthood. Unexpectedly, these effects extended equally to the contralateral, uninjected side, demonstrating a fundamental role for interhemispheric connections in cortical maturation.

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Section: Discussionmentioning

confidence: 99%

Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

Caleo¹,

Restani²,

Gianfranceschi³

et al. 2007

J. Neurosci.

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“…Intrahippocampal injection of botulinum toxin E resulted in inhibition of seizure activity in rat models of epilepsy (Costantin et al, 2005;Bozzi et al, 2006). Botulinum toxin A2 reduces incidence of seizures in mouse models of temporal lobe epilepsy (Kato et al, 2013).…”

Section: B Cleavage Of Snares By Clostridial Toxinsmentioning

confidence: 99%

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Kavalali

2017

Pharmacol Rev

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“…Unilateral intrahippocampal bolus injections of botulinum neurotoxin E have been shown to attenuate electrographic seizure activity in rats produced by intrahippocampal kainic acid 57,58. The toxin also reduced behavioral limbic seizures resulting from systemic kainic acid injection.…”

Section: Cedmentioning

confidence: 99%

Convection-Enhanced Delivery in the Treatment of Epilepsy

Rogawski

2009

Neurotherapeutics

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Summary: Convection-enhanced delivery (CED) is a novel drug-delivery technique that uses positive hydrostatic pressure to deliver a fluid containing a therapeutic substance by bulk flow directly into the interstitial space within a localized region of the brain parenchyma. CED circumvents the blood-brain barrier and provides a wider, more homogenous distribution than bolus deposition (focal injection) or other diffusion-based delivery approaches. A potential use of CED is for the local delivery of antiseizure agents, which would provide an epilepsy treatment approach that avoids the systemic toxicities of orally administered antiepileptic drugs and bystander effects on nonepileptic brain regions. Recent studies have demonstrated that brief CED infusions of nondiffusible peptides that inhibit the release of excitatory neurotransmitters, including -conotoxins and botulinum neurotoxins, can produce long-lasting (weeks to months) seizure protection in the rat amygdala-kindling model. Seizure protection is obtainable without detectable neurological or behavioral side effects. Although conventional diffusible antiepileptic drugs do confer seizure protection when administered locally by CED, the effect is transitory. CED is a potential approach for seizure protection that could represent an alternative to resective surgery in the treatment of focal epilepsies that are resistant to orally-administered antiepileptic drugs. The prolonged duration of action of nondiffusible toxins would allow seizure protection to be maintained chronically with infrequent reinfusions.

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Action of botulinum neurotoxins in the central nervous system: Antiepileptic effects

Cited by 42 publications

References 52 publications

Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets

Convection-Enhanced Delivery in the Treatment of Epilepsy

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