Neutrophil extracellular traps (NETs) infiltrate haematoma and surrounding brain tissue after intracerebral haemorrhage: A post-mortem study.

AIMS

Because of their prothrombotic and neuroinflammatory effects, neutrophils and neutrophil extracellular traps (NETs) represent interesting therapeutic targets for spontaneous intracerebral haemorrhage (sICH). We investigated the presence, spatial and temporal distribution of NETs in a human sICH post-mortem study.

METHODS

From 2005 to 2019, all sICH patients who came to autopsy within the first month after stroke were included and grouped according to the timing of death: 72 h, 4-7 days, 8-15 days and >15 days after ICH onset. Paraffin-embedded tissue was extracted from four strategic areas: haematoma, peri-haematomal area, ipsilateral surrounding brain tissue and a control contralateral area. Myeloperoxidase and histone H3 citrulline were immunolabelled to detect neutrophils and NETs respectively.

RESULTS

Neutrophils were present in the brains of the 14 cases (4 men, median age: 78 years) and NETs were found in 7/14 cases. Both neutrophils and NETs were detected within the haematoma but also in the surrounding tissue. The appearance of neutrophils and NETs was time-dependent, following a two-wave pattern: during the first 72 h and between 8 and 15 days after ICH onset. Qualitative examination showed that neutrophils and NETs were mainly located around dense fibrin fibres within the haematoma.

CONCLUSIONS

These observations provide evidence for NETs infiltration in the brain of patients who die from sICH. NETs might interact with early haemostasis within the haematoma core, and with the surrounding neuroinflammatory response. These findings open research perspectives for NETs in the treatment of sICH injuries.