Title : Use of NMDA antagonists for the treatment of TBI
Abstract:
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among individuals under 45 years of age worldwide. In the United States alone, approximately 1.7 million traumatic events occur annually, resulting in 50,000 deaths. This high prevalence of TBI poses a significant socioeconomic and healthcare burden due to its association with long-term disability and death in young adults.
The mechanisms underlying secondary brain injury in TBI are complex and involve various processes. These include alterations in cerebral perfusion, activation of inflammatory cytokines, and excitotoxicity. The kinetic energy generated during TBI causes mechanical deformation of the axons, leading to the depolarization of cell membranes and the release of neurotransmitters, such as glutamate. This excessive release of glutamate initiates a process called excitotoxicity, wherein there is a rapid influx of calcium into the cell cytoplasm caused by ionotropic receptors activated. This influx of calcium activates harmful signaling cascades, ultimately leading to cell apoptosis.
Thus, the neurotoxicity generated by glutamate release could be avoided by N-methyl-D-aspartate receptor antagonists. As there is a theoretical potential for administration to this intervention improving outcomes following traumatic brain injury, clinical pre clinical research has focused on the role of NMDA receptors (NMDAR) in TBI
In this presentation the results of clinical and preclinical studies on the use of NMDA antagonists for the treatment of TBI will be discussed. The data and the protocol of a systematic review in progress will be discussed.
Audience Take Away
- Gain a deep understanding of the complex mechanisms underlying secondary brain injury in traumatic brain injury (TBI), including alterations in cerebral perfusion, inflammatory cytokine activation, and excitotoxicity
- Recognize the role of glutamate release and excitotoxicity in TBI, and how they contribute to harmful signaling cascades and cell apoptosis
- Understand the potential benefits of N-methyl-D-aspartate receptor antagonists in preventing neurotoxicity caused by glutamate release and improving outcomes in TB
- Identify new targets and strategies for developing effective interventions and therapeutic approaches for TBI
