Neuroinflammation in the acute phase after subarachnoid hemorrhage: A translational approach

Abstract

A subarachnoid haemorrhage from a ruptured aneurysm is a severe type of stroke that affects approximately 1000 patients every year in the Netherlands. Neuroinflammation is one of the mechanisms that may contribute to brain damage after the haemorrhage. In this thesis, we conducted various studies to investigate the inflammatory response in the brain after aneurysmal subarachnoid haemorrhage (aSAH). We show that two types of cells, microglia and astrocytes, become activated after aSAH. These cells may provide a therapeutic target in the future as they may play a role in the development of brain damage. We also show how white blood cells counts change in the cerebrospinal fluid after aSAH. Such knowledge may help to interpret cerebrospinal fluid parameters in patients if nosocomial bacterial meningitis or ventriculitis is suspected. Subsequently, we set-up a clinical trial to investigate the safety and efficacy of eculizumab, a complement C5 inhibitor, in patients with aSAH. The primary outcome was a ≥ 55% decrease in C5a concentration in the cerebrospinal fluid of aSAH patients. Patients who received eculizumab did not have a ≥55% decrease in C5a levels in the cerebrospinal fluid. The study did not reveal new safety concerns, except for a C. albicans drain-related infection. Lastly, we asked patients and family members how consent to participate in an acute care trial should be asked. In certain circumstances, it was considered acceptable by patients and family members to first enrol a patient into a study and ask for consent in a later phase. Altogether, the results of each of these studies contribute to better understand neuroinflammation after a subarachnoid haemorrhage. In addition, the results help us understand how clinical trials can be conducted in acute conditions.