Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients

Severe traumatic brain injury (TBI) is characterized by a high mortality and poor outcome. The pathomechanisms involved are cytokine-mediated proinflammatory and anti-inflammatory reactions and significant cerebral microcirculatory disorders. The role of endothelin 1 (ET-1), a very potent vasoconstrictive peptide, in the deterioration of cerebral perfusion after trauma is still unclear. The presented study investigated the changes in ET-1 in the cerebrospinal fluid (CSF) and plasma after TBI in humans, with special regard to the presence of subarachnoid hemorrhage (SAH) and clinical outcome. Twenty patients with TBI were consecutively enrolled into the study, 10 patients without SAH (TBI group) and 10 patients with SAH (TBI-H group). Paired samples of plasma and CSF were collected for 10 days after trauma. Analysis of the ET-1 concentrations showed that TBI is associated with initially increased ET-1 values in plasma (TBI, day 1; TBI-H, days 2-3) and significantly increased (P < 0.05, vs. control) CSF concentrations (TBI, days 1-2; TBI-H, days 1-3) in the first days after trauma. In the further time course, ET-1 values declined in both groups, reaching reference values in plasma. The CSF values remained significantly (P < 0.05 vs. control) elevated. Both groups showed a second peak on the beginning of the second week after trauma in plasma and CSF. Whereas plasma concentrations failed to reach significance, CSF values showed a significant peak on day 7 in both groups. The TBI-H patients had significantly (P < 0.05) higher values in the secondary peak compared with patients of the TBI group. The kinetics of traumatic SAH-dependent ET-1 needs to be assessed in further investigations.