Plasma biomarkers for epileptogenesis and epileptic seizures

Research Opportunity
PhD, Masters by Research, Honours
Project Status
Future
Department
Medicine and Radiology
Location
Royal Melbourne Hospital
Supervisor Email Number Webpage
Dr. Idrish Ali idrish.ali@unimelb.edu.au
Prof. Terence O'Brien

Project Details

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 neuroinflammation, 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 expression in blood or protein expression levels in plasma 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 timepoints to direct preventive therapies against epileptogenesis- including neuroinflammation modulating therapies altering the M/M2 balance within the brain glia.

Research Opportunities

This research project is available to PhD, Masters by Research, Honours students to join as part of their thesis.
Please contact the supervisor to discuss your options.



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

Royal Melbourne Hospital