Intense olfactory stimulation blocks seizures in an experimental model of epilepsy

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.

Behavioral and EEGraphic Characterization of the Anticonvulsant Effects of the Predator Odor (TMT) in the Amygdala Rapid Kindling, a Model of Temporal Lobe Epilepsy

“…Taken together, the results of this study are associated to the multinational research consortium Epilepsies with External Modification of Ictogenesis ( EpExMo ), aimed at collaborating with the knowledge associated to basic mechanisms and clinical features of epilepsy inhibited or triggered by external sensory or cognitive stimuli. Our current experiments are in fact absolutely coherent with previous studies ( 7 , 8 , 15 – 18 , 20 , 57 , 90 – 92 ), adding consistent data to the literature. Furthermore, our findings certainly represent a partial component that will collaborate to the understanding of efficacy of odorants in the seizure response, with potential translational impact.…”

“…Similarly, experimental data also 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). Conversely, the induction of seizures by olfactory stimulation has also been reported, in both animal models and in the clinic (19)(20)(21)(22).…”

“…The olfactory stimulus occurred in the same chamber of the electrical stimulus, for this, 5 μl of liquid (water or TMT) was soaked under a piece of filter paper and kept inside the chamber completely closed during 30 min [temporal and chemical parameters assessed in a previous study ( 18 )]. Subsequently, the filter paper was removed and the animals were placed inside the chamber.…”

Rodent Brain Pathology, Audiogenic Epilepsy

“…This phenomenon is the result of ascending influences from the (abnormally functioning) brain-stem structures of AE-prone animals. At the same time there are two clear indications that the reverse influences (i.e., from the forebrain to brain stem) also exist, as strong olfactory stimulation resulted in the decrease of AE-seizure intensity [ 101 , 102 ].…”

Efeitos do tratamento com canabidiol (CBD) em modelos genéticos de epilepsias: estudos comportamentais, farmacológicos e eletrofisiológicos

“…Análise neuroetológica foi aplicada a fim de se comparar detalhes da expressão comportamental das crises audiogênicas dos grupos WAR-KA-CBD e WAR-KA-Vei. O método de análise neuroetológica utilizado se baseia na análise segundo à segundo, providenciando, portanto, resultados comportamentais que vão além de meros índices, como a sequência e o poder de interação entre os pares de comportamentos (DELFINO-PEREIRA et al, 2018;GARCIA-CAIRASCO et al, 1992)…”