Abstract

Background: Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity.Objective: We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala rapid kindling (ARK).Materials and Methods: Wistar male rats (280–300 g) underwent stereotaxic surgery for electrode implantation in piriform cortex (PC), hippocampal formation (HIP), and amygdaloid complex (AMYG). Part of the animals was exposed to a saturated chamber with water or TMT, while others had ARK and olfactory exposure prior to the 21st stimulus. Behavioral responses were measured by traditional seizure severity scales (Racine and Pinel and Rovner) and/or by sequential analysis/neuroethology. The electrographic activity of epileptogenic limbic networks was quantified by the occurrence of the first and second EEG afterdischarges, comparing the 1st and 21st stimulus. The spectral analysis [Fast Fourier Transform (FFT)] of the first afterdischarge was performed at the 21st stimulus.Results: TMT olfactory exposure reduced the seizure severity in kindled rats, altering the displayed behavioral sequence. Moreover, TMT decreased the occurrence of first and second afterdischarges, at the 21st stimulus, and altered the spectral features.Conclusions: Both behavioral and EEGraphic evaluations indicated that TMT, a potent molecule with strong biological relevance, in fact, “predator odor,” suppressed the epileptiform activity in limbic networks.

Highlights

  • Epilepsy is a hyperexcitable brain disease, characterized by the persistent predisposition to generate epileptic seizures [for full definition, see [1]] and by the neurobiological, psychological, cognitive, and social consequences [2]

  • We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala rapid kindling (ARK)

  • TMT (Stimulus and TMT) significantly reduced the Limbic index (LI) compared to the 20th stimulus, but there was no difference for the Stimulus and Water group in the 5 min after electrical stimulation (POST)-period

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Summary

Introduction

Epilepsy is a hyperexcitable brain disease, characterized by the persistent predisposition to generate epileptic seizures [for full definition, see [1]] and by the neurobiological, psychological, cognitive, and social consequences [2]. A promising alternative in the pool of therapeutic approaches is olfactory stimulation (odor therapy) capable to modulate, block, or even induce seizures. Experimental data evidenced promising results, as shown by Ebert and Löscher [17], utilizing the olfactory stimulation with toluene (TOL), an aversive odor, capable of decreasing the seizures’ susceptibility in amygdala kindling, even with electrical stimulation 20% above of threshold. The latter report was strongly supported by our experimental findings, confirming the TOL anticonvulsant effects, in the acute and chronic (kindled) audiogenic seizures, in Wistar Audiogenic Rat (WAR) animals [18]. The induction of seizures by olfactory stimulation has been reported, in both animal models and in the clinic [19,20,21,22]. Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity

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