Subarachnoid Haemorrhage Leads to Desialilation of Hippocampal Glycocalyx Followed by Complement System Activation

Background: Subarachnoid haemorrhage (SAH) – the accumulation of blood in the subarachnoid space - is the most fatal stroke, with a 40% mortality rate and 95% of survivors suffer permanent disabilities. Hippocampal neuroinflammation following SAH has been recognized as a potential cause of post-SAH syndrome, and the complement system, in particular, has been identified as a major player. Levels of C1q, the activating protein of the classical pathway of the complement system, has been found to be significantly higher in hippocampus (HPC) following SAH. However, mechanisms of C1q activation, the first step in complement cascade activation, remain unknown.
Aim: Our earlier data demonstrated that SAH triggers hippocampal neuroinflammation, which involves microglia activation and release of sialidase “trimming” terminal glycocalyx sialic acid (SA) and exposing potential binding sites for C1q.
Method: To test this hypothesis in perforation of the Willis circle model of SAH we employed immunohistochemical staining using various lectins to detect changes in sialylation and sialidase inhibitor (SI) treatment to explore changes in the hippocampal layers in SAH and Sham mouse brains.
Results: Levels of C1q increased significantly in the hippocampal molecular layer (ML) and stratum lacunosum moleculare (SLM) (P