Combinational Antioxidant Therapy to Prevent the Development of PTE
Abstract
Head trauma, or traumatic brain injury, is the worldwide leading cause of disability and death among children and young adults, as well as a growing problem in the elderly. Traumatic brain injury can result in the death of nerve cells and changes in brain tissue that may eventually lead to the development of epilepsy (chronic seizures), termed post-traumatic epilepsy. This has not only acute but also long-term detrimental consequences affecting proper thinking and memory, increasing the risks of developing disabilities and comorbidities in patients’ later lives, affecting their life span. In recent years, traumatic brain injury has been recognized as a significant and growing problem among military personnel and Veterans who are highly exposed to head injury and are at high risk for developing post-traumatic epilepsy. Despite enormous scientific efforts to explore the mechanisms underlying long-term consequences of traumatic brain injury and to develop therapies that can preserve brain tissue, no specific therapeutic options are yet available for patients. Importantly, post-traumatic epilepsy is one of the only brain diseases in which people at risk can be identified, and yet there is no prophylactic treatment to prevent the development of the disease in those at risk. Moreover, currently there are no diagnostic markers available to predict patients at risk to develop epilepsy following head injury. Recent studies indicate that free radicals, unstable atoms that can damage cells, also play a part in aging and cancer, are key players in such cell and tissue damage. Excessive free radical production starts within hours and continues over days after injury. Therefore, blocking the processes that contribute to the free radical’s production and increasing the antioxidant defenses of nerve cells may be effective in preventing the consequence damage following brain injury, including the development of epilepsy. We have some compelling early evidence that free radical-induced brain damage can be prevented by blocking a specific source of free radicals within the brain and by increasing the nerve cells’ ability to mop up these free radicals. Therefore, a group of epilepsy researcher, traumatic brain injury researchers and imaging scientists joined forces and formed a research group to investigate the role of oxidative stress following traumatic brain injury in experimental animals. The goals of the proposed research are to develop novel biomarkers (that can distinguish healthy subjects from diseased ones) and therapeutic options by comparing the two approaches and a combination of both, to determine the most effective way of preventing cell death and tissue damage following brain injury induced in rats. For this purpose, the research group will use a unique telemetry system, which allows video-and-wireless electrocorticography recording enabling monitoring of both behavior and brain activity, and novel brain imaging technology, enabling depiction of subtle changes in brain vascular function. These technologies will be applied in combination with state-of-the-art cognitive tests and histological analysis. Rats will be studied for a very long term (12 months) post-injury in order to provide a comprehensive understanding of the mechanisms leading to the development of epilepsy in an attempt to apply the new knowledge for developing novel means for early prediction of the disease as well as means to suppress the damage along the way. The pharmacological drugs applied in this study are in advanced clinical investigations for indications other than epilepsy and will be tested as a therapy to prevent the development of epilepsy and memory problems following weight drop in animals, a condition that mimics focal brain injury. Vascular dysfunction will be assessed with our novel translational magnetic resonance imaging (MRI) technology, already U.S. Food and Drug Administration (FDA)-approved, thus translation to the clinical scenario may
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210677
Entities
People
- Tawfeeq Shekh-Ahmad
Organizations
- Hebrew University of Jerusalem
- United States Army