Blood Glutamate Scavenging: First Emergency Neuroprotective Treatment for Spinal Cord Injury
Abstract
Neurotrauma, especially traumatic brain and spinal cord injuries (SCI), are a common and unfortunate consequence of modern life. A combination of the enemy s increasingly extensive use of explosive devices as well as the enhanced survivability among combat-injured Soldiers has led to higher incidents of SCI in recent combat compared with past wars. Most Soldiers usually live with the consequences of their injury for decades. Currently, no efficient treatment can reduce the neurological damage. Therefore, an urgent need exists for novel strategies and drugs to alleviate the devastating conditions of neurotrauma victims and to help their families. Glutamate is the most widely distributed neurotransmitter in the brain. Numerous studies over the past decades have consistently shown that high levels of glutamate in the brain can damage and kill neurons. Recognition of this phenomenon (excitotoxicity) has spawned intensive research in the fields of neurotrauma and has demonstrated that high levels of extracellular glutamate in the brain lead to an overload of calcium within the first few hours, resulting in the deaths of neurons and significant motor impairment. Reducing central nervous system (CNS) glutamate levels shortly after the injury will inhibit the cascade of toxic events and significantly reduce secondary damage, improve the functional recovery, and the regenerative process after neurotrauma. However, there are currently no clinical treatments available to promote neuronal regeneration and functional recovery after SCI. The aim of this proposed research is to evaluate the applicability and therapeutic efficacy of the first emergency neuroprotective approach to treat SCI. We have developed a radically different strategy to reduce excess CNS glutamate by reducing its levels in the blood circulation, which has been shown to be extremely effective in stroke, traumatic brain injury, and Paraoxon intoxication in animal models. Recently, we have demonstrated the significant neuroprotective effect of the treatment followed by improved motor function in hemisection and compression SCI animal models. Our study will pioneer the testing of this approach on contusion SCI. Since no side effects have been reported following the initial toxicology study, the novel approach hereby proposed may be of high clinical significance for the treatment of Soldiers with neurotrauma in the very near future. Clearly, the treatment of SCI is a complex therapy, combining acute and chronic treatment. Therefore, we will examine the effectiveness of the proposed treatment at the chronic phase of the injury in conjunction with scar removal surgery. The proposed novel treatment is of particular therapeutic relevance, because it demonstrates a strong neuroprotective effect and a safe toxicology profile. Therefore, the proposed therapeutic strategy has high feasibility to be tested in clinical trials shortly after completing the current study and potentially result in a smaller incomplete injury followed by better functional outcome in injured Soldiers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110517
Entities
People
- Angela Ruban
Organizations
- Tel Aviv University
- United States Army