The Role of Markers of Inflammation in Traumatic Brain Injury

Abstract

Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia, and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (Interleukin-1, Tumor Necrosis Factor, Interleukin-6), the anti-inflammatory cytokines (IL-4, Interleukin-10, and TGF-beta), and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following Traumatic brain injury (TBI), the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring, and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality, or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This review article will discuss the evidence from both clinical and laboratory studies exploring the validity of immune markers as a correlate to classification and outcome following TBI.

Inhibition of Monoacylglycerol Lipase Prevents Chronic Traumatic Encephalopathy-like Neuropathology in a Mouse Model of Repetitive Mild Closed Head Injury

“…Neuroinflammation is a critical factor inducing neuropathogenesis following TBI. 12,13 This means that resolving neuroinflammation may prevent or reduce the incidence of CTE development after rmTBI. Endogenous cannabinoids display antioxidant, anti-inflammatory, and neuroprotective properties.…”

“…12,13 To determine whether proinflammatory cytokines are elevated and astroglial cells are activated in our animal model of rmCHI and whether these inflammatory responses can be suppressed by MAGL inactivation, we assessed messenger RNA expression of proinflammatory markers vimentin (Vim) and cytokines, including IL-1β, IL-6 and TNFα, in the ipsilateral brain using qPCR analysis 4 days after the first injury and glial reactivity 8 days after the first TBI. As seen in Figure 2A, Immunoreactivity of Iba1 (microglial marker) and (C) glial fibrillary acidic protein (GFAP) (astrocytic marker) in the ipsilateral cortex (CTX), hippocampal CA1, and dentate gyrus (DG) was determined using immunostaining analysis.…”

“…Proinflammatory markers such as cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNFα), and chemokines released from reactivated astroglial cells and infiltrated leukocytes in the brain and cerebrospinal fluid are robustly elevated after TBI. 12,13 The extent of neuroinflammatory response in TBI seems to be closely correlated with the outcome. 13 Although the primary injury immediately following TBI is not preventable, the secondary injury provides a window for interventions to prevent further brain damage after the primary injury.…”

“…12,13 The extent of neuroinflammatory response in TBI seems to be closely correlated with the outcome. 13 Although the primary injury immediately following TBI is not preventable, the secondary injury provides a window for interventions to prevent further brain damage after the primary injury. Appropriate and timely intervention during this critical window following the primary injury after TBI may significantly reduce secondary brain damage and eventually prevent occurrence of CTE.…”

Exosome platform for diagnosis and monitoring of traumatic brain injury

“…The differential patterns of localization of TNF-a receptors in neuronal and glial cells, their state of activation and the downstream effectors are all thought to play an important role in determining whether TNF-a will exert a beneficial or harmful effect on the CNS. Additionally, TNF-a contributes to the tissue injury induced by neutrophils by directly activating them, as well as by increasing the expression of such molecules as E-selectin, which cause the activated neutrophils to adhere to the surface of the endothelial cells [24]. It has also been shown that the inhibition of neutrophil adhesion to the endothelial cell surface markedly reduces the severity of the CNS injury induced by compressive trauma.…”