ROLE OF AUTOANTIBODIES IN LONG-TERM OUTCOME AND COGNITIVE FUNCTION AFTER STROKE

Stroke is the second leading cause of death worldwide and the primary cause of long-term disability in adults. With increasing life expectancy, the global burden of stroke is expected to rise, yet therapeutic options remain limited and time-restricted. Ischemic stroke, caused by cerebral artery occlusion, leads to irreversible brain damage and triggers a sustained inflammatory response involving both innate and adaptive immune cells, including antibody differentiation and preparation in the ischemic brain.

This project investigates post-stroke antibodies, focusing on their characterization, CNS targets, and effects on cognitive function. Using in vitro and in vivo approaches, plasma cells were isolated from a stroke-induced mouse model, and recombinant monoclonal antibodies were generated for functional studies. Effects on neuronal cells, brain integrity, and cognition are being evaluated, alongside analyses of antibodies from stroke patients to identify clinically relevant targets. To distinguish the impact of pre-existing versus newly generated autoantibodies, recombinant candidate antibodies are administered either before or after experimental stroke induction in mice. The analysis focuses on multiple immunoglobulin isotypes targeting a range of CNS antigens, including neuronal, astrocytic, endothelial, and other brain-resident cell populations. This work aims to define the pathological role of CNS-directed autoantibodies in post-stroke cognitive decline and long-term neurological outcome. Understanding post-stroke humoral immune responses may reveal novel therapeutic targets to improve recovery after stroke.