Management of Traumatic Brain Injury: From Present to Future

Abstract

TBI (traumatic brain injury) is a major cause of death among youth in industrialized societies. Brain damage following traumatic injury is a result of direct and indirect mechanisms; indirect or secondary injury involves the initiation of an acute inflammatory response, including the breakdown of the blood–brain barrier (BBB), brain edema, infiltration of peripheral blood cells, and activation of resident immunocompetent cells, as well as the release of numerous immune mediators such as interleukins and chemotactic factors. TBI can cause changes in molecular signaling and cellular functions and structures, in addition to tissue damage, such as hemorrhage, diffuse axonal damages, and contusions. TBI typically disturbs brain functions such as executive actions, cognitive grade, attention, memory data processing, and language abilities. Animal models have been developed to reproduce the different features of human TBI, better understand its pathophysiology, and discover potential new treatments. For many years, the first approach to manage TBI has been treatment of the injured tissue with interventions designed to reduce the complex secondary-injury cascade. Several studies in the literature have stressed the importance of more closely examining injuries, including endothelial, microglia, astroglia, oligodendroglia, and precursor cells. Significant effort has been invested in developing neuroprotective agents. The aim of this work is to review TBI pathophysiology and existing and potential new therapeutic strategies in the management of inflammatory events and behavioral deficits associated with TBI.

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

“…Many efforts have been made to find a possible therapeutic approach by targeting secondary injury processes, including calcium channel blockers, corticosteroids, excitatory amino acid inhibitors, NMDA receptor antagonist, free radical scavengers, magnesium sulfate and growth factors [ 56 ]. In particular, several compounds showed interesting anti-inflammatory effects, reducing (i) proinflammatory cytokines, (ii) microglial activation and (iii) some transcription factors and receptors involved in neuroinflammation, such as Nuclear factor kappa B (NF-κB) and Toll-like receptor-4 (TLR4) [ 57 ] ( Table 1 ). Many of these strategies provided positive effects in reducing neuroinflammation in experimental models of TBI, but failed when tested in clinical trials, therefore, no effective therapy currently exists for the treatment of neuroinflammation.…”

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma

“…TBI may lead to unconsciousness, headaches, fatigue, sensory problems, and cognitive decline. Neurotrauma causes contusions, hemorrhage, activation of glial cells, neurons, and mast cells, increases proinflammatory cytokine/chemokine release, blood–brain barrier (BBB) dysfunction, axonal damage, and neuroinflammation 2,14–17 . TBI can increase the risk of neurodegenerative diseases and dementia 2 …”

The Negative Allosteric Modulator EU1794-4 Reduces Single-Channel Conductance and Ca2+ Permeability of GluN1/GluN2A N-Methyl-d-Aspartate Receptors

“…Despite decades of work in both industry and academia, there are no approved therapies for treatment of ischemic stroke other than the dissolution or removal of the vessel clot in a fraction of patients (Awad et al, 2020;Turner et al, 2020). Likewise, there are no approved therapies that can reduce neuronal death following traumatic brain injury (Crupi et al, 2020).…”