Neuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side

Abstract

Head trauma is the most common cause of disability in young adults. Known as a silent epidemic, it can cause a mosaic of symptoms, whether neurological (sensory-motor deficits), psychiatric (depressive and anxiety symptoms), or somatic (vertigo, tinnitus, phosphenes). Furthermore, cranial trauma (CT) in children presents several particularities in terms of epidemiology, mechanism, and physiopathology-notably linked to the attack of an immature organ. As in adults, head trauma in children can have lifelong repercussions and can cause social and family isolation, difficulties at school, and, later, socio-professional adversity. Improving management of the pre-hospital and rehabilitation course of these patients reduces secondary morbidity and mortality, but often not without long-term disability. One hypothesized contributor to this process is chronic neuroinflammation, which could accompany primary lesions and facilitate their development into tertiary lesions. Neuroinflammation is a complex process involving different actors such as glial cells (astrocytes, microglia, oligodendrocytes), the permeability of the blood-brain barrier, excitotoxicity, production of oxygen derivatives, cytokine release, tissue damage, and neuronal death. Several studies have investigated the effect of various treatments on the neuroinflammatory response in traumatic brain injury in vitro and in animal and human models. The aim of this review is to examine the various anti-inflammatory therapies that have been implemented.

Keywords: neuroinflammation; neuroprotection; therapeutics; traumatic brain injury.

Figure 1

Schematic representation of post-traumatic neuroinflammation. The rupture of the blood-brain barrier, the release of alarmines (or DAMPS: Damage Associated Molecular Patterns) by injured cells and the production of cytokines are at the origin of an endothelial, astrocytic, and microglial activation with a change in conformation of the microglial cells which take an amoeboid conformation and migrate towards the injured area. This response to trauma is both localized and generalized with secondary recruitment of the peripheral immune system. BBB: blood brain barrier; CXCL: chemokine ligand; DAMPS: damaged associated molecular patterns; IL: interleukin; HMGB1: high mobility group bow 1; iNOS: inducible nitric oxide synthase; PRR: pattern recognition receptor; PS100: protein S 100; TBI: traumatic brain injury; TGF: transforming growth factor; TNF: tumor necrosis factor.

Figure 2

Chronology of post-traumatic lesions. The TBI is responsible for a primary mechanical lesion that can be transformed into a tertiary lesion via neuro-inflammatory mechanisms and thus generate a chronic post-traumatic encephalopathy. TBI: traumatic brain injury.