Comparative review of NETosis in Mouse and Human Models with a Focus on Subarachnoid Hemorrhage
Yezhong Lu, MD1, Sina Hemmer2, Philips Hendrix2
1st luke university health network, 2Neurosurgery, Geisinger Health system
Objective:

Recent studies have found that neutrophil extracellular traps(NETs) are key players in the pathophysiology of subarachnoid hemorrhage, with research in both animal and human subjects elucidating the roles of NETs in exacerbating inflammation. We highlight the current knowledge and insights from animal models studying NETs in subarachnoid hemorrhage, alongside the current landscape in human research to map out the parallels and highlight the barriers between findings in both models, underscoring the need for translational research to bridge these gaps. 

Background:

NETs are implicated in various disease pathophysiology including subarachnoid hemorrhage. Neutrophils, traditionally viewed as simple immune responders, have shown complex behaviors in immune modulation and response. NETs is a key player in the progression of subarachnoid hemorrhage, Treatments inhibiting NET formation has shown potential in animal models. 

 

Design/Methods:

A comprehensive literature search was conducted using PubMed and Google Scholar from January 2000 to December 2023, focusing on terms like "Neutrophil Extracellular Traps," "Subarachnoid Hemorrhage," and "Biomarkers." Data were synthesized into tables that outline the pathophysiological roles of NETs, their potential as biomarkers, and therapeutic implications in both animal models and human studies.

 

Results:

NETs play a critical role across a spectrum of diseases, with particular relevance in subarachnoid hemorrhage where they exacerbate inflammation and microthrombosis. Our review highlights the effectiveness of DNase I and PAD4 inhibitors in animal models, suggesting their translational potential for clinical application. While human studies are limited, they support findings from animal models, indicating a promising correlation between NET biomarkers and disease severity.

Conclusions:

NETs are instrumental in advancing our understanding of subarachnoid hemorrhage. Animal studies suggest that targeting NETs could mitigate brain injury and improve outcomes. However, translating these findings to human applications is challenging due to physiological and pathophysiological variations. Enhanced translational research, integrating both human and animal model data, is essential for developing effective therapies.

10.1212/WNL.0000000000208949
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.