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.

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The role of markers of inflammation in traumatic brain injury.

Objective: To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. Methods: Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] ≤ 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. Results: The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 μg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 μg/L) and NSE (>21.7 μg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). Conclusions: These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury.

Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury

Background and Purpose—This study was aimed at the comparative analysis of serum concentrations of glial fibrillary acidic protein (GFAP) and protein S-100B in patients with acute stroke. Methods—We investigated 32 patients with stroke symptoms consistent with cerebral ischemia in the anterior territory of vascular supply. Serial venous blood samples were taken after admission to the hospital and during the first 4 days after onset of stroke. Evaluation of lesion topography and volume of infarcted brain area was based on cranial CT data. The patients’ clinical status was consecutively evaluated by the National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index score at discharge from the hospital. Results—Protein S-100B and GFAP release was found to be significantly correlated (r=0.96; P<0.001). The release of both biochemical markers was associated with the volume of brain lesions (S-100B: r=0.957, P<0.0001; GFAP: r=0.955, P<0.0001) and the neurological status at discharge from the hospital ...

Release of glial tissue-specific proteins after acute stroke : A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein.

Research indicates that glial fibrillary acidic protein (GFAP), part of the astroglial skeleton, could be a marker of traumatic brain injury (TBI). S100B, an astroglial protein, is an acknowledged marker of TBI. Our goal was to analyze the relationship of GFAP/S100B to brain damage and outcome, and to compare the accuracy of GFAP/S100B for prediction of mortality after TBI. Our prospective study included 92 patients admitted 0.5 cm (p 25 mL (p 0.5 cm (p or = 25 (p or = 60 than CPP 70 than MAP < or = 70 mm Hg, and in GOS 4-5 than GOS 1 (p < 0.0005). Both measurement of GFAP and S100B is a useful non-invasive means of identifying brain damage with some differences based on the pattern of TBI and accompanying multiple trauma and/or shock.

GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome.

https://www.annemergmed.com/article/S0196-0644(11)01545-9/pdf

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.

Glial fibrillary acidic protein (GFAP), found only in glial cells of the central nervous system (CNS) (1)(2), was first isolated by Eng et al. (1) in 1971. GFAP is a monomeric molecule with a molecular mass between 40 and 53 kDa (3)(4) and an isoelectric point between 5.7 and 5.8 (2). GFAP represents the major part of the cytoskeleton of astrocytes. DeArmond et al. (5) reported on the spontaneous degradation of GFAP in vitro and in vivo; under physiological conditions, GFAP polymerizes spontaneously to astrofibrils with a length of 0.8–1.06 μm.

Numerous reports in the literature document the usefulness of measuring GFAP in cerebrospinal fluid (CSF) as a specific indicator of CNS pathology (6)(7)(8)(9)(10)(11)(12)(13). Measuring GFAP in blood would have clinical advantages over CSF measurements; however, to our knowledge, the only method attempted to date to measure GFAP in blood (14) was not successful.

We describe the results of measuring the concentrations of both GFAP and S-100 protein in the blood of patients with acute severe head trauma and healthy controls, using the dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) system for detection of GFAP (DELFIA can also be used to measure the concentration of GFAP in CSF).

Blood samples were obtained from 25 patients (19 males and 6 females; ages, 16–72 years; mean age, 38.6 ± 19.0 years) who were admitted <24 h after severe head trauma (a Glasgow Coma Scale score of ≤6 on admission). Three samples were obtained from each patient: the first sample was obtained on admission to the hospital, the second was obtained 24 h after the head injury, and the third was obtained 48 h after the injury.

Blood samples were also obtained from 70 healthy blood donors …

Hanna Hagenström

Papers

Measurement of Glial Fibrillary Acidic Protein in Human Blood: Analytical Method and Preliminary Clinical Results