Markers of Inflammation in Brain and Blood as Predictors of Post-Traumatic Epilepsy Risk?
Abstract
Epilepsy is a common chronic brain disorder in which patients have frequent seizures and often also suffer from mental health conditions, such as depression and anxiety, as well as memory loss. Post-traumatic epilepsy is epilepsy that occurs after a brain injury, and its incidence depends on how severe the brain injury was and the age of the person at the time. The incidence of post-traumatic epilepsy is much higher in people from the military. Post-traumatic epilepsy produces a large, lifelong burden affecting individuals’ quality of life, as well as having an impact on the economics of society. There is a strong need for therapies that are designed to prevent the development of post-traumatic epilepsy. However, at present there are no means to predict who will develop epilepsy after brain injury, providing a challenge in performing or trying any such preventive treatments. This is because around 20% of people develop epilepsy after moderate-severe head injury, and although some risk factors have been identified, it is impossible to direct treatment only to the patients that would benefit, making the trial very expensive and unachievable. There is increasing evidence that inflammation of the brain after a traumatic brain injury leads to changes in its structure and function that lead to the development of epilepsy. Our experiments, along with those of other researchers, using animal models suggest that measuring the level of inflammation in the brain and blood soon after brain injury can predict the later development of post-traumatic epilepsy and any associated behavioral problems. The research hypothesis I am looking to test in this project is that inflammation in the brain (measured by imaging techniques) and in the blood (measured using biochemical techniques) will predict the development of post-traumatic epilepsy and neuropsychiatric comorbidities. To test this hypothesis, we will use a rat model that mimics what is seen in the clinical setting for people who develop post-traumatic epilepsy (i.e., in around 25%-30% of rats). After modeling brain injury in rats, we will perform brain imaging and collect blood samples at early time points after brain injury to measure the brain and blood inflammation markers. We will also perform behavioral tests 6 months after the initial injury and then classify if rats have epileptic or not. The pattern of inflammation observed during the early period after brain injury will then be related to the animals that develop epilepsy and behavioral abnormalities in the chronic disease phase. The blood tests and brain imaging being evaluated in our animal study are highly translatable to the clinic. One of the imaging techniques (magnetic resonance imaging) is already part of clinical practice in hospitals for patients with moderate-to-severe brain injuries. Based on the outcomes of our study the parameters of measurement could be adjusted to include brain inflammation. Similarly, our second proposed imaging technique (positron emission tomography) is also use clinically to measure brain inflammation in patients with other brain diseases. Although this is not part of standard clinical practice for acutely injured patients with brain injury, our study outcomes could lead to its inclusion in current clinical practice. Prof. O’Brien, who is the mentor for this project, is a world-leading neurologist and is running several clinical trials testing biomarkers for post-traumatic epilepsy and trials of new therapy for epilepsy. He is in an opportune position to advise on the pathway to translate the outcomes of this study into clinical practice. Moreover, our findings also have the potential to influence epilepsy research in pharmaceutical companies developing and testing preventive treatments for epilepsy. Currently, the focus is mainly in models where all animals develop epilepsy; therefore, no consideration is given to post-traumatic epilepsy where only 20%-30% animals develop epilepsy. Fo
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110927
Entities
People
- Idrish Ali
Organizations
- Monash University
- United States Army