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Published on: February 14, 2025
Intense olfactory stimulation blocks seizures in an experimental model of epilepsy
Polianna Delfino-Pereira1, Poliana Bertti-Dutra2, Eduardo Henrique de Lima Umeoka2
1Neurosciences and Behavioral Sciences Department, Ribeirão Preto School of Medicine, Universiy of São Paulo, Hospital das Clínicas, Campus Universitário S/N, 4° Andar, Ribeirão Preto, SP CEP: 14048-900, Brazil.
Abstract:
There are reports of patients whose epileptic seizures are prevented by means of olfactory stimulation. Similar findings were described in animal models of epilepsy, such as the electrical kindling of amygdala, where olfactory stimulation with toluene (TOL) suppressed seizures in most rats, even when the stimuli were 20% above the threshold to evoke seizures in already kindled animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic seizures induced by acute acoustic stimulation, although it also expresses limbic seizures when repeated acoustic stimulation occurs - a process known as audiogenic kindling (AK). The aim of this study was to evaluate whether or not the olfactory stimulation with TOL would interfere on the behavioral expression of brainstem (acute) and limbic (chronic) seizures in the WAR strain. For this, animals were exposed to TOL or saline (SAL) and subsequently exposed to acoustic stimulation in two conditions that generated: I) acute audiogenic seizures (only one acoustic stimulus, without previous seizure experience before of the odor test) and II) after AK (20 acoustic stimuli [2 daily] before of the protocol test). We observed a decrease in the seizure severity index of animals exposed only to TOL in both conditions, with TOL presented 20s before the acoustic stimulation in both protocols. These findings were confirmed by behavioral sequential analysis (neuroethology), which clearly indicated an exacerbation of clusters of specific behaviors such as exploration and grooming (self-cleaning), as well as significant decrease in the expression of brainstem and limbic seizures in response to TOL. Thus, these data demonstrate that TOL, a strong olfactory stimulus, has anticonvulsant properties, detected by the decrease of acute and AK seizures in WARs.
Insights
Olfactory stimulation with toluene suppressed seizures in Wistar Audiogenic Rats. This finding suggests toluene has anticonvulsant properties, reducing both acute and kindled seizures in this epilepsy model.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Olfactory stimulation is reported to prevent epileptic seizures in humans and animal models.
- Toluene (TOL) has previously shown anticonvulsant effects in amygdala-kindled rats.
- The Wistar Audiogenic Rat (WAR) strain exhibits acute tonic-clonic and chronic limbic seizures.
Purpose of the Study:
- To investigate the anticonvulsant potential of olfactory toluene stimulation in the WAR strain.
- To assess TOL's effect on acute audiogenic seizures and audiogenic kindling (AK).
Main Methods:
- WARs were exposed to toluene (TOL) or saline (SAL) before acoustic stimulation.
- Seizure severity was evaluated under two conditions: acute audiogenic seizures and after AK.
- Neuroethological analysis was used to examine behavioral changes.
Main Results:
- Toluene exposure significantly decreased seizure severity in both acute and AK conditions.
- TOL, presented 20 seconds before acoustic stimuli, reduced brainstem and limbic seizures.
- Behavioral analysis showed increased exploration and grooming, and decreased seizure expression.
Conclusions:
- Olfactory stimulation with toluene exhibits significant anticonvulsant properties in the WAR strain.
- Toluene effectively reduces both acute and chronic seizure manifestations in this epilepsy model.
- These findings highlight the therapeutic potential of olfactory stimulation in epilepsy management.
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