Analysis of the consequences of injury to the LP nucleus of the thalamus in epilepsy. A possible biological marker for SUDEP?

Abstract

The possible contribution of the thalamus to the onset and spreading of epileptic discharges has been extensively discussed and thalamic atrophy has been found in patients with temporal lobe epilepsy (TLE), with the anterior and posterior thalamic nuclei being mainly affected. In this sense, it is necessary to elucidate whether structural changes in the lateral-posterior (LP) nucleus occurs during the process of epileptogenesis or whether these changes occurs after epilepsy startup. As a first objective, this project aims to map the neuronal and glial expression in the thalamic LP nuclei during different periods of the pilocarpine model of epilepsy, through analysis of optical densitometry. Another question is whether these thalamic changes reported previously may be associated with functional and structural cardiovascular alterations such changes in heart rate variability (HRV), changes in intrinsic neural network of the heart or changes in miRNAs expression in myocardial tissue. These points may be related with the mechanisms behind sudden unexpected death in epilepsy (SUDEP). Furthermore changes in the ECG of patients with epilepsy may be different from each other. So one may ask what are the mechanisms and structures responsible for this finding. May the thalamus have an important role in this scenario? In this sense, we have previously performed HRV analysis before and after injury of the LP nucleus of the thalamus in animals without epilepsy, and we have found changes in HR, RMSSD and SDNN parameters. The present project also aims to extend these findings, by investigating HRV parameters before and after injury of the LP nucleus of the thalamus in animals with epilepsy. Therefore, given the role of thalamic LP nucleus in the course of epilepsy and the effective participation of the LP nucleus in controlling cardiac functions, the present project aims to investigate whether HRV and cardiac morphological and molecular parameters are altered in animals with repeated spontaneous seizures associated with lesions in the LP nucleus. The results are expected to contribute to a better understanding of the pathophysiological mechanisms involved in epilepsy, especially with regard to the mechanisms involved in the occurrence of SUDEP. Furthermore, the results may provide the basis for possible interventions to control cardiovascular changes thereby decreasing the risk of SUDEP.