It has been hypothesized that immunoactivation may contribute to brain damage and affect outcome after traumatic brain injury (TBI). In order to determine the role of inflammation after TBI, we studied the interrelationship of the immune mediators sICAM-1 and IL-6 with the levels of S-100beta and neuronal specific enolase (NSE), both recognized markers of brain damage. In addition, the extent and type of cerebral injury and the neurological outcome were related to these measured markers of injury. An evident elevation of S-100beta (range of means: 2.7-81.4 ng/mL) and NSE (range of means: 2.0-81.3 ng/mL) was observed in CSF of all 13 patients during the first 3 posttraumatic days and decreased over 2 weeks. In parallel, the production of sICAM-1 (range of means: 0.7-11.9 ng/mL) and IL-6 (range of means: 0.1-8.2 ng/mL) was also markedly enhanced in CSF. The CSF means of S-100beta and NSE per patient correlated with IL-6 (r = 0.60, p < 0.05; and r = 0.64, p < 0.05, respectively), whereas the corresponding means in serum showed a significant correlation only between NSE and IL-6 (r = 0.56, p < 0.05). Maximal CSF values of NSE and sICAM-1 correlated with each other (r = 0.57, p < 0.05). The contusion sizes assessed on the CT scans correlated with the means of S-100beta (r = 0.63, p < 0.05) and NSE (r = 0.71, p < 0.05) in CSF and with the mean of S-100beta in serum, although not statistically significant (r = 0.52, p = 0.06), but not with serum NSE. Interestingly, linear regression analysis demonstrated that means of S-100beta in CSF (r = 0.78, p = 0.002) and serum (r = 0.82, p < 0.001) correlated with the GOS. These results indicate that the elevation of these parameters in CSF depends on the extent of injury and that S-100beta may be a predictor of outcome after TBI, whereas NSE reflects better the inflammatory response.

The excitatory transmitters glutamate and aspartate become toxic whenever their extracellular levels are increased because of neuronal, glial and endothelial impairment. Taurine, a volume-regulating amino acid, is released upon excitotoxin-induced cell swelling. Our aim was to investigate if glutamate and aspartate in cerebrospinal fluid (CSF) reveal neuropathology in neurological patients, and if taurine unmasks glutamate-mediated toxicity. Glutamate and aspartate are doubled in viral meningitis, acute multiple sclerosis (MS) and myelopathy compared with control subjects and patients with peripheral facial nerve palsy. These levels do not coincide with a disturbed blood-brain barrier, as estimated by the albumin ratio, are independent of their precursors (glutamine, asparagine) and are not associated with cell lysis. Taurine is significantly increased in meningitis, acute MS, and myelopathy, suggesting glutamate-mediated toxicity. Analysis of transmitters in lumbar CSF can be used to identify patients with cerebral and spinal pathology who might benefit from specific receptor-modulating agents.

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Barbiturate coma does not unequivocally preserve energetic stability despite successful suppression of neuronal activity. Despite the use of barbiturate coma in patients with refractory intracranial hypertension, persistent release or impaired uptake of glutamate may be associated with continuous anaerobic metabolism, as shown by increases in cerebrospinal fluid hypoxanthine and lactate levels.

Increased extracellular glutamate levels are related to glial and neuronal damage. Glutamate-mediated toxicity is limited by glial uptake and metabolic transformation of glutamate to glutamine and the energetic compounds alanine and lactate which are utilized by surrounding neurons. Under in vitro conditions, barbiturates have been shown to reduce glutamate uptake and its further metabolism, possibly impeding metabolic coupling between astrocytes and neurons. The aims were to investigate if under clinical conditions, the barbiturate thiopental reduces important detoxification of glutamate, resulting in lower CSF glutamine, alanine and lactate levels as opposed to patients receiving midazolam. During long-term administration of thiopental and midazolam, pathologically elevated ventricular CSF glutamate levels were associated with significantly increased glutamine and alanine levels up to 14 days after trauma. CSF lactate, however, remained normal. These data suggest that long-term administration of thiopental and midazolam under clinical conditions does not impede enzymatic activities responsible for detoxification and metabolism of glutamate.