Abstract T P395: Complement Activation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage - An Autopsy Study

Abstract

Background: The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. It has been hypothesized that an inflammatory response in the subarachnoid space and microthrombosis contribute to DCI. Previous studies showed that plasma levels of complement factors are associated with DCI and functional outcome after aSAH. We performed an autopsy study to investigate the relationship between complement activation, microthrombosis and DCI. Methods: In autopsy material from 7 patients who died from DCI, we isolated 9 areas of cerebral infarction and 15 areas without infarction. From autopsy material of 5 controls (myocardial infarction: n=3; heart failure: n=1; pulmonary embolism: n=1) we isolated 15 corresponding areas. We performed immunohistochemistry to investigate the presence of C1q, C3c, and fibrin(ogen) (which is strongly correlated with microthrombosis). Optical density measurements were used for quantitative assessments. Optical density values were compared between areas with infarction, without infarction, and controls, and analyzed with a Mann-Whitney U test. Spearman correlation tests were performed to investigate the relationships of C1q and C3c with fibrin(ogen). Results: Optical density values of C1q, C3c, and fibrin(ogen) were higher in areas of infarction than in areas without infarction or controls (Table 1, p<0.001 for all comparisons). Correlations were found between C1q and fibrin(ogen) (r=0.73, p<0.001) and C3c with fibrin(ogen) (r=0.74, p<0.001). Conclusion: Our results show that areas of cerebral infarction in patients with aSAH have more complement activation and microthrombosis than areas without infarction or control brains. A strong correlation was found between complement activation and microthrombosis. Future studies are needed to investigate if drugs targeting complement activation decrease the risk of DCI and improve outcome after aSAH.