Early or primary injury due to brain aggression, such as mechanical trauma, hemorrhage or is-chemia, triggers the release of damage-associated molecular patterns (DAMPs) in the extracellular space. Some DAMPs, such as S100B, participate in the regulation of cell growth and survival but may also trigger cellular damage as their concentration increases in the extracellular space. When DAMPs bind to pattern-recognition receptors, such as the receptor of advanced glycation end-products (RAGE), they lead to non-infectious inflammation that will contribute to necrotic cell clearance but may also worsen brain injury. In this narrative review, we describe the role and ki-netics of DAMPs and RAGE at the acute phase of brain injury. We searched the MEDLINE database for “DAMPs” or “RAGE” or “S100B” and “traumatic brain injury” or “subarachnoid hemorrhage” or “stroke”. We selected original articles reporting data on acute brain injury pathophysiology, from which we describe DAMPs release and clearance upon acute brain injury, and the implication of RAGE in the development of brain injury. We will also discuss the clinical strategies that emerge from this overview in terms of biomarkers and therapeutic perspectives

Background: Early brain injuries (EBI) are one of the most important causes of morbidity and mortality after subarachnoid hemorrhage. At admission, a third of patients are unconscious (spontaneously or sedated) and EBI consequences are not evaluable. To date, it is unclear who will still be comatose (with severe EBI) and who will recover (with less severe EBI) once the aneurysm is treated and sedation withdrawn. The objective of the present study was to determine the diagnostic accuracy of S100B levels at hospital admission to identify patients with severe neurological consequences of EBI. Methods: Patients were consecutively included in this prospective blinded observational study. A motor component of the Glasgow coma score under 6 on day 3 was used to define patients with severe neurological consequences of EBI. Results: A total of 81 patients were included: 25 patients were unconscious at admission, 68 were treated by coiling. On day 3, 12 patients had severe consequences of EBI. A maximal S100B value between admission and day 1 had an area under the receiver operating characteristic curve (AUC) of 86.7% to predict severe EBI consequences. In patients with impaired consciousness at admission, the AUC was 88.2%. Conclusion: Early S100B seems to have a good diagnostic value to predict severe EBI. Before claiming the usefulness of S100B as a surrogate marker of EBI severity to start earlier multimodal monitoring, these results must be confirmed in an independent validation cohort.