EMERGING LEADER FELLOWSHIP AWARD
£249,569 over 39 months, awarded in 2022
Investigating the role of microglia in drug-resistant seizures, sudden death and memory function in epilepsy
Dr Amol Bhandare
University of Warwick
Epilepsy is characterized by seizures – sudden bursts of electrical activity in the brain. Epilepsy affects half a million people in the UK. One-third live with uncontrolled seizures and many suffer from cognitive disabilities. Tragically, each year approximately 600 people die from sudden unexpected death in epilepsy (SUDEP).
Microglia – the brain’s immune cells – regulate the function of neurons. However, research including Dr Bhandare’s previous work suggests that microglia initially protect neurons during seizures, but their activation is detrimental during chronic epilepsy.
"Microglia – the non-neuronal brain cells – are the double‑edged sword in epilepsy. Seizures activate microglia that either act like a security system or produce excessive neuroinflammation and eat neuronal branches called synapses. Using advanced imaging technique, I will find out how microglia function changes during progression of epilepsy and contribute to drug-resistant seizures, memory loss and sudden unexpected death in epilepsy (SUDEP). Marketed drug (minocycline) can stop microglia activation and could provide immediate benefits to people with epilepsy.
The research team will investigate whether microglial function changes in epilepsy, leading to a progressive decrease in seizure threshold, memory disruption and compromised activity of the brain cells that control the function of the heartbeat and breathing. The underlying mechanism of this change in microglial function, from normal to detrimental, needs to be better understood.
The researchers will use advanced imaging techniques in experimental models of epilepsy to record the actions of neurons and microglia. The team will then use the commonly prescribed antibiotic minocycline, to see if it can prevent epileptic activity in microglia. This drug has been previously shown to have an anticonvulsant effect in people with drug resistant epilepsy, so if successful it could be rapidly translated into clinical practice.
This project’s findings will provide the rationale to repurpose the commonly prescribed drug, minocycline, to modify microglial action, and potentially prevent seizures. This will allow testing of this drug in clinical settings and could provide a new treatment for patients at increased risk of SUDEP and those with drug-resistant seizures and cognitive abnormalities.
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