The Use of Fourier Transform Infrared Microspectroscopy for the Determination of Biochemical Anomalies of the Hippocampal Formation Characteristic for the Kindling Model of Seizures.

Marzena M Rugiel,Joanna G Chwiej,Agnieszka K Drozdz,Justyna Kutorasińska,Zuzanna K Setkowicz,Krzysztof J Janeczko

doi:10.1021/acschemneuro.1c00642

Marzena M Rugiel, Joanna G Chwiej + Show 4 more

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https://doi.org/10.1021/acschemneuro.1c00642

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Abstract

The animal models of seizures and/or epilepsy are widely used to identify the pathomechanisms of the disease as well as to look for and test the new antiseizure therapies. The understanding of the mechanisms of action of new drugs and evaluation of their safety in animals require previous knowledge concerning the biomolecular anomalies characteristic for the particular model. Among different models of seizures, one of the most widely used is the kindling model that was also applied in our study. To examine the influence of multiple transauricular electroshocks on the biochemical composition of rat hippocampal formation, Fourier transform infrared (FT-IR) microspectrosopy was utilized. The chemical mapping of the main absorption bands and their ratios allowed us to detect significant anomalies in both the distribution and structure of main biomolecules for electrically stimulated rats. They included an increased relative content of proteins with β-sheet conformation (an increased ratio of the absorbance at the wavenumbers of 1635 and 1658 cm–1), a decreased level of cholesterol and/or its esters and compounds containing phosphate groups (a diminished intensity of the massif of 1360–1480 cm–1 and the band at 1240 cm–1), as well as increased accumulation of carbohydrates and the compounds containing carbonyl groups (increased intensity of the bands at 1080 and 1740 cm–1, respectively). The observed biomolecular abnormalities seem to be the consequence of lipid peroxidation promoted by reactive oxygen species as well as the mobilization of glucose that resulted from the increased demand to energy during postelectroshock seizures.

Highlights

Animal models of seizures are used both to develop new anticonvulsants and to observe processes associated with epileptogenesis.[1,2] An optimal experimental model of epileptic seizures should provide a reliable way of inducing a stable, epileptic-like condition as well as predictability of response to treatment.[2,3] Among different animal models of seizures, post status epilepticus (SE) models and kindling models should be mainly distinguished
Characteristic feature of post SE models is amygdala damage and hippocampal sclerosis, including cytoarchitectonic disorganization and death of pyramidal neurons.[1,4−6] Numerous studies have indicated that these changes resemble anomalies occurring in the temporal lobe areas of patients suffering from temporal lobe epilepsy (TLE).[3,5,7−10]
For animals subjected to electrical stimulation, we observed significantly increased intensity of the 1740 cm−1 absorption band originating from the compounds containing carbonyl groups, which may point at the elevated concentration of aldehydes as a result of lipid peroxidation and, the same, seem to confirm the hypothesis concerning the kindling-induced oxidative stress

Summary

Introduction

Animal models of seizures are used both to develop new anticonvulsants and to observe processes associated with epileptogenesis.[1,2] An optimal experimental model of epileptic seizures should provide a reliable way of inducing a stable, epileptic-like condition as well as predictability of response to treatment.[2,3] Among different animal models of seizures, post status epilepticus (SE) models and kindling models should be mainly distinguished. Kindling models are based on chronic exposure to a subliminal stimulus (chemical or electrical) of proconvulsive nature.[3] As a result of 1−3 weeks of electrical stimulation of the limbic system structures or repeated administration of the proconvulsive agent, the seizure threshold is reduced and seizures with a gradually increasing severity and duration appear.[1,3] The occurrence of spontaneous convulsions in this model is a rare phenomenon; stimulus-induced seizures are usually the subject of research. The nature of recorded seizures as well as their sensitivity to pharmaceuticals are very similar in post SE and kindling models.[1,3,11] in the latter, neuropathological changes typical for TLE such as hippocampal sclerosis are not noted.[12,13] On the other hand, in the brains of rats subjected to repeated stimulation, as observed

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