14 Sep 2017

Potential breakthrough in treating post-traumatic epilepsy in children

Dr Bridgette Semple researches children's epilepsy
Researchers have discovered that an anti-inflammatory compound may help improve cognitive function and reduce vulnerability to epileptic seizures in children who have suffered a brain injury. They have described a new animal model of epilepsy that develops after brain injury, particularly in young brains, that will hopefully enable doctors to better target treatment.

Published in The Journal of Neuroscience, the study was led by Dr Bridgette Semple from the University of Melbourne & Department of Medicine at the Royal Melbourne Hospital, and Melbourne Brain Centre.  Bridgette will be moving to the Central Clinical School as part of the new Department of Neurosciences headed by Professor Terry O'Brien in October 2017.


Dr Semple worked with colleagues in Melbourne and the University of California San Francisco to
improve the medical understanding of epilepsy following traumatic brain injury in childhood.

Post-traumatic epilepsy (PTE) is relatively common after paediatric traumatic brain injury. It involves two or more unprovoked seizures more than one week after traumatic brain injury (TBI), and is difficult to manage and treat.

Until now, knowledge of PTE has been limited. Using an animal model, the researchers found that
following paediatric trauma the brain reproduces many neuropathological and seizure-like hallmarks
characteristic of epilepsy.

“Secondly, we demonstrated that targeting the acute inflammatory response reduces cognitive
impairments, the degree of neuropathology and seizure susceptibility after paediatric brain injury in
mice,” Dr Semple says.

“More specifically, this study also tests the ability of an anti-inflammatory compound, IL-1Ra, to prevent epilepsy after early life brain injury. We found that treatment within the first week after injury was sufficient to improve cognitive function and reduce vulnerability to seizures when mice had reached adulthood.

“As this drug is clinically approved for other uses, and in clinical trial for adult traumatic brain injury, our findings provide evidence that its use in brain-injured children may improve long-term outcomes in these patients.”

From a scientific perspective, this research also confirms an important link between the inflammatory
response and seizure development after injury.

The researchers are now investigating another anti-inflammatory drug to evaluate if it has a similar
benefit in this model, and future studies aim to understand the precise biological mechanisms by which such treatments may influences PTE.

The research was funded by an NHMRC Early Career Fellowship, a University of Melbourne Early Career Grant and funding from the Rebecca L. Cooper Medical Research Foundation.

Reference
Semple BD, O'Brien TJ, Gimlin K, Wright DK, Kim SE, Casillas-Espinosa PM, Webster KM, Petrou S, Noble-Haeusslein LJ. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain. 2017 Aug 16;37(33):7864-7877. doi: 10.1523/JNEUROSCI.0982-17.2017. Epub 2017 Jul 19.
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