TITLE:
In Vitro Hippocampal Electrophysiology and in Vivo Quantitative EEG Revealed Robust Neurophysiological Effects of the Antivertigo-Agent Vertigoheel® in a Rat Study
AUTHORS:
Wilfried Dimpfel, Bernd Seilheimer, Leonie Schombert
KEYWORDS:
EEG, Rat Model, Central Nervous System, Vertigo, VH-04, Neurophysiology, Hippocampus, Multitarget, Fast Fourier Transformation
JOURNAL NAME:
Neuroscience and Medicine,
Vol.10 No.4,
December
27,
2019
ABSTRACT: Vertigo is a common symptom with impact on daily life. Vertigoheel® (VH-04) has demonstrated to be effective for Vertigo in former studies. This paper aims to investigate the mode of action of the medicinal product VH-04 in the rat brain. In an in vitro study neurophysiological recording from hippocampal slices from adult male Sprague Dawley® rats was performed in order to substantiate a possible direct effect on the brain of VH-04 in different concentrations. In an in vivo cross-over study with 11 Fischer 344®rats, a neurophysiological method was applied to systemically analyse VH-04’s activity in the rat brain. This method combines quantitative assessments of telemetrically transmitted field potentials after drug treatment with subsequent discriminant analysis to classify the compound. The database used for the analysis of classification contained numerous chemicals and medicinal products of different dosages, all tested in the same paradigm, which is continuous wireless monitoring of the EEG of freely moving rats before and after drug intake. Following single stimuli on the Schaffer collaterals in the presence of VH-04 in different concentrations, in vitro responses of pyramidal cells increased depending on the VH-04 concentration (0.25 - 4 ml/L). Results were statistically significant for concentrations above 2.5 ml/L. Long-term potentiation was only marginally affected. Out of several specific glutamate receptor antagonists the effect of VH-04 was only antagonized by AMPA and kainic acid receptor-mediated signalling. Their enhancement indicates better information processing in the hippocampus, a brain structure primarily involved in memory processes. The in vivo characterisation of VH-04-induced changes in EEG-signatures of four brain areas (the frontal cortex (FC), the hippocampus (HC), the striatum (ST) and the reticular formation (RF)) revealed a dose-dependent attenuation of delta, theta, alpha 2 and beta 1 waves. The subsequent discriminant function analysis classified the VH-04 EEG-signature into a subset of cognition-enhancing medicinal products.