Studies on inflammation in the acute phase of aneurysmal Subarachnoid Hemorrhage
Sammanfattning: Spontaneous subarachnoid hemorrhage (SAH) accounts for 5% of all strokes and is associated with high morbidity and mortality. Rupture of intracranial aneurysm is the cause in 85% of cases. After aneurysm repair to prevent rebleeding, patients are treated at Neuro-Intensive Care Units for multimodal monitoring and interventions aiming to treat the primary injury and prevent/treat secondary complications. The acute phase after SAH can roughly be divided in the periods of Early Brain Injury (EBI) and Delayed Cerebral Ischemia (DCI). EBI refers to the events occurring within the first 72h from SAH and includes the primary injury and its direct consequences. DCI occurs in 30-40% of SAH patients between days 4-14 after SAH and leads usually to neurologic deterioration. The term Delayed Ischemic Neurologic Deficit (DIND) is used almost synonymously. Cerebral vasospasm was earlier considered to be the main (if not the sole) contributor to DCI. It is now widely accepted that DCI is a multifactorial phenomenon where inflammation plays a pivotal role. Numerous molecular, cellular, and genetic aspects of inflammation have been analyzed in both clinical and preclinical experimental studies in different compartments, such as plasma, cerebrospinal fluid (CSF) and cerebral extracellular fluid (through microdialysis).The aim of the studies included in this thesis was to analyze different molecular and clinical aspects of the inflammatory response in the acute phase of SAH and provide new insights in understanding the complex pathophysiology of SAH. In Paper I, a pilot study of intrathecal and systemic inflammation was conducted by measuring levels of Interlukin-6 in CSF and plasma of 44 patients. In Paper II, a comprehensive inflammatory profile of SAH was illustrated by simultaneously measuring 92 inflammation-related proteins in CSF of 29 patients using multiplex Proximity Extension Assay technology for the first time in SAH research. Twenty chemokines included in the same panel as in Paper II were further analyzed regarding their associations with clinical parameters and outcome in Paper III. Finally, in Paper IV two common inflammatory markers, C-reactive protein (CRP) and leukocytes, were analyzed in blood of 552 patients regarding their temporal trajectories and correlations with factors reflecting EBI and SAH complications. In general, the results support the notion that more severe bleeding is associated with stronger cerebral and systemic inflammatory response. Some molecules have also emerged as potential predictors of complications and outcome.
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