Stroke, or cerebrovascular accident, is a neurological disorder caused by a disruption of blood flow to the brain. Strokes are broadly classified into two main types: ischemic and hemorrhagic. Ischemic strokes occur when a cerebral blood vessel becomes blocked, whereas hemorrhagic strokes result from the rupture of a blood vessel, leading to bleeding in the brain. When this bleeding occurs within the brain tissue itself, it is referred to as an intracerebral hemorrhage (ICH).

ICH is a devastating condition with high mortality and morbidity, affecting over two million people worldwide each year. Approximately 40% of patients die within the first month, and only slightly more than half of survivors regain functional independence within one year. In addition to the immediate damage, ICH triggers secondary injury processes that can lead to long-term complications, such as post-stroke epilepsy.

The two primary causes of spontaneous ICH are deep perforating vasculopathy and cerebral amyloid angiopathy. Bleeding from deep perforating vasculopathy is typically the result of chronic hypertension. Cerebral amyloid angiopathy, on the other hand, is a condition in which amyloid-beta deposits accumulate in the walls of small and medium-sized cerebral blood vessels, weakening them and increasing the risk of hemorrhage.

At 4Brain, our mission is to advance the understanding of ICH and its consequences. To investigate the long-term effects of ICH on the brain and their relation to increased disease risk, we use the collagenase rat model, in which ICH can be induced under controlled conditions. Combining neuroimaging techniques (MRI and PET) with histological analyses, we study brain changes over time. Continuous video-EEG monitoring allows us to investigate the development of post-ICH epilepsy. A better understanding of ICH pathology is essential for the development of improved therapeutic strategies.

Cerebral amyloid angiopathy (CAA) is a small-vessel disease caused by the progressive deposition of amyloid-β. Amyloid-β  is a protein fragment that naturally forms in the brain. andIn healthy brains, it is cleared without causing any harm in healthy brains. In some people however, amyloid-β can build up and cause problems. In CAA, amyloid-β builds up in the walls of cortical and leptomeningeal blood vessels. This makes the vessels weaker and more prone to rupturing. Clinically, CAA may present with spontaneous intracerebral hemorrhages, transient focal neurological episodes, and progressive cognitive decline.

Alzheimer’s disease (AD), characterized by a progressive decline in memory and cognition, is also caused by amyloid-β deposition. In AD, however, amyloid-β accumulates in the brain parenchyma rather than in the vessel walls. CAA and AD often co-occur in the same patient. Notably, CAA has been identified as a major risk factor for adverse effects associated with emerging AD treatments (anti-amyloid antibodies).