Endothelin-1:
Endothelin is a long-acting, highly powerful vasoconstrictor found throughout the brain. Endothelin helps to the maintenance of CBF by working through its receptors, ETA and ETB, and is regarded as a major auto regulating peptide (Graves & Kreipke, 2015). ET-1 is a peptide that is generated and released by the vascular endothelium in response to substances like reactive oxygen species (ROS), cytokines, and thrombin. ET-1 is also known to be produced by leukocytes and macrophages (Fassbender et al., 2000). Although endothelin-1 is widely acknowledged as a strong vasoconstrictor, its precise role in autoregulation appears to be more elusive. Adults with elevated ET-1 levels in the CSF after TBI had poor clinical outcomes, including death, permanent vegetative state, or severe debility, according to data acquired by (Maier, Lehnert, Laurer & Marzi, 2007) Endothelin-1 has been associated to reduced CBF and poor prognosis post damage in several animal models of TBI. According to the findings of the following studies (Armstead & Kreipke, 2011; Beuth, Kasprzak, Kotschy, Woźniak, Kulwas & Sniegocki, 2001; Kreipke, Morgan, Roberts, Bagchi & Rafols, 2007; Lampl, Fleminger, Gilad, Galron, Sarova-Pinhas & Sokolovsky, 1997; Salonia et al., 2010; Sato & Noble, 1998), TBI disrupts autoregulatory systems by increasing endothelin-1-mediated vasoconstriction. Further studies revealed that, while the drug significantly reduced vasospasm, it did not result in significant improvements in the patient’s condition, showing that vasospasm may not be the primary cause of poor outcome after subarachnoid hemorrhage but early brain injury may also be a factor. To clarify the precise role of ET-1 in the development of EBI after SAH, more research is needed.