Plasma biomarkers for epileptogenesis and epileptic seizures

Introduction: Epilepsy is a devastating neurological disorder that affects around 50 million people worldwide. Patients with acquired epilepsy, one of the most common forms of epilepsies, often suffer from comorbid neuropsychiatric and cognitive disorders. Around 1/3rd of the cases are not effectively controlled by current epilepsy therapy, which is only symptomatic and do not inhibit the progression of disorder. These patients acquire epilepsy as a consequence of a brain insult (e.g. head trauma, encephalitis, glioma, stroke or status epilepticus (SE)) following a period of months to years. This period of epileptogenesis (disease development) clearly represents an important therapeutic window for preventative treatment and therefore, a large body of preclinical epilepsy research has invested heavily on developing preventive disease-modifying therapy for epilepsy. However, the reliable identification of patients at high risk is an unmet urgent clinical need, to be able to effectively target these preventive therapies. Studies in animal model have characterised in details various pathological events during the epileptogenesis process including neuro-inflammation, neurodegeneration as well as modulation of neuronal circuitry via axonal/ dendritic modifications. The aim of this project is to identify those neuropathological changes in blood with the goal of developing them as a biomarker for epileptogenesis and chronic seizures. We have collected blood samples from different cross sectional time points covering the period of epileptogenesis as well as during the established epilepsy phase in a rat model of temporal lobe epilepsy following kainic acid induced SE. The histological evaluations covering the neuroinflammation and neurodegeneration during the epileptogenesis as well as the seizure burden using video/EEG monitoring during the chronic period has already been investigated. This project will involve evaluating the time course of mRNA or protein expression levels for neuroinflammatory (mainly the M1 and M2 markers)/neurodegeneration/axonal damage markers in blood samples and compare them to control animals. In addition, we will relate them to acute pathological findings during epileptogenesis phase as well as to the seizure burden/severity during chronic epilepsy. Expected outcome: 1. We will be able to identify the time course for the development of blood levels of mRNA/protein markers for brain pathology. 2. Identify if the blood markers during the chronic epilepsy phase are predictive of seizure burden 3. Identify appropriate time points to target for future blood and brain imaging studies for evaluating predictive biomarker of epilepsy. 4. Potentially identify the time points to direct preventive therapies against epileptogenesis- including neuro-inflammation modulating therapies altering the M/M2 balance within the brain glia.