Prevention of Post-Traumatic Epilepsy by Inhibiting the Initiation of Innate Immune Reaction
Abstract
Posttraumatic epilepsy (PTE) is a disabling neurological disorder that develops in some patients after a traumatic brain injury (TBI). It is poorly controlled by the currently available antiepileptic drugs and constitutes one of the major conditions that compromise functional outcome and quality of life in TBI patients. Because the mechanism is not well understood, this disease is difficult to control and cannot be prevented at present. There is an urgent need to develop novel treatments for PTE prevention. Inflammation has been found to play an important role in epilepsy development and seizure induction, but our knowledge on this is limited. Recently, we made a novel finding that a type of immune cell called natural killer T cells (NKT) may be critical for PTE development. These cells are important in inflammatory responses, but we found that these cells may play an important role in inducing PTE. For example, if we genetically delete these cells in mice, the development of PTE is also prevented. More importantly, our early study showed that statins, a type of widely used lipid lowering medicines, can block the signal that activates these NKT cells. Therefore, we will further study how these immune cells cause epilepsy development and how statins may prevent PTE. The goal of this project is to study where and how NKT cells cause PTE development and how to target these cells for PTE prevention. In our research team, Dr. Xiaoming Jin is an experienced neuroscientist with expertise in studying the mechanism and prevention of PTE; Dr. Randy Brutkiewicz is an immunologist with expertise in innate immune function, particularly the signaling and activation of NKT cells. This highly interdisciplinary collaboration brings innovation and supports the success of the project. The current project will make several contributions to the PTE research field. It will reveal a new mechanism about whether and how NKT cells cause the development of PTE after a TBI, so that we can obtain new knowledge and develop new approaches to prevent or treat it. Because inflammation is such a universal response after brain injuries, our study will be generally applicable to epilepsy development after different types of TBI. The study on statins will not only discover how this drug may control inflammation, but also provide a new method using statins for the prevention of PTE. Particularly, because statins are a U.S. Food and Drug Administration (FDA)-approved medication and are quite tolerable with few adverse effects, our studies may be quickly translated into the clinic, so that Soldiers and patients with a TBI may use statins for preventing PTE. Therefore, this project will have a strong potential for translational applications to the military, Veteran, and civilian communities.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310213
Entities
People
- Xiaoming Jin
Organizations
- Indiana University
- United States Army