The Role of Neutrophil Extracellular Traps in Early Microthrombosis and Brain Injury After Subarachnoid Hemorrhage in...

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Microthrombosis is a key factor in secondary brain injury following subarachnoid hemorrhage (SAH).
• The precise mechanisms driving microthrombosis in SAH remain incompletely understood.
• Neutrophil extracellular traps (NETs) are implicated in thrombosis but their role in SAH is unclear.

Purpose of the Study:

• To investigate the involvement of neutrophil extracellular traps (NETs) in the development of microthrombosis after experimental SAH.
• To explore NETs as a potential therapeutic target for early brain injury (EBI) following SAH.

Main Methods:

• Subarachnoid hemorrhage (SAH) was induced in mice using an endovascular perforation model.
• NET formation was assessed by measuring citrullinated histone H3 (CitH3) levels and co-localization with microthrombi.
• Neutrophil depletion (anti-Ly6G) and DNase I treatment were employed to inhibit NETs and assess their impact.

Main Results:

• Elevated CitH3 levels and co-localization with microthrombi were observed in the cerebral cortex post-SAH.
• Both neutrophil depletion and DNase I treatment significantly reduced NETs, microthrombi, and ameliorated neurological deficits, brain edema, BBB disruption, and neuronal injury.
• DNase I treatment improved early cortical perfusion and attenuated cerebrospinal fluid (CSF) flow by reducing paravascular microthrombi.

Conclusions:

• NETs are significantly associated with early microthrombosis in the context of SAH.
• Inhibition of NETs and associated microthrombi shows therapeutic potential for mitigating early brain injury after SAH.
• Targeting NETs represents a promising novel therapeutic strategy for SAH.