A narrative review of pathophysiology and therapeutic frontiers in early brain injury followed by aneurysm subarachnoid hemorrhage

Background: Early brain injury (EBI) is a critical gap in the evolution preceding subarachnoid hemorrhage, developing within the first 72 h after aneurysm rupture. EBI involves a complex sequence of physiopathological processes. These include disruption of the blood–brain barrier (BBB), impaired cerebral perfusion, and molecular pathways that cause vascular and neuronal injury. Understanding these events during the EBI remains a critical step toward improving neurocritical, neurosurgical, and neurological care and future therapies. Methods: A literature review was conducted with a focus on the EBI, its physiopathological processes, therapeutic frontiers, and implications for future neurocritical care and improved patient outcomes. A systematic evaluation of peer-reviewed publications from the previous decade was conducted across PubMed, Scopus, and Web of Science databases. Results: The cascade of physiopathological events following aneurysmal rupture is characterized by an abrupt increase in intracranial pressure, followed by reduced cerebral perfusion, and involves neuroinflammation, BBB disruption, and oxidative stress, pathways that appear to be mediated by Toll-like receptor 4/nuclear factor-kappa B, matrix metalloproteinase-9, and gasdermin D. The endothelial dysfunction and excitotoxicity induce cerebral edema, neuronal death, and cortical spreading depolarizations. Conclusion: EBI remains a critical knowledge gap in the management of aneurysmal subarachnoid hemorrhage, and understanding its pathophysiology may enable earlier, mechanism-based interventions and improve neurological outcomes.