Single clip: An improvement of the filament-perforation mouse subarachnoid haemorrhage model

ABSTRACT

Objective: The endovascular filament-perforation model turned out to become the most popular one for the reproduction of prominent pathophysiological features observed after human subarachnoid haemorrhage (SAH). However, few studies have considered methods that may minimize surgically induced injury. This study described an improved and simplified surgical procedure in which a single clip is placed at the external carotid artery (ECA).

Method: Male C57BL/6 mice were given either a classic endovascular filament SAH model, improved endovascular filament SAH model or sham injury. Multiple strategies, including MRI with T₂-weighted imaging and ¹⁸F-FDG PET/CT scanning, were performed to compare the improved and classic SAH models.

Results: The new method of filament model resulted a typical pathophysiological progress of early brain injury (EBI), including cerebral oedema, blood brain barrier (BBB) disruption, neuronal apoptosis and microglia activation. The improved SAH model is characterized by a shorter operation time (15.65 ± 0.64 min vs. 21.75 ± 0.94 min), reduced surgically induced injury (decreased ¹⁸F-FDG standardized uptake values (SUV): 1.7 ± 0.07 vs. 2.02 ± 0.11), and stable cerebral perfusion before SAH.

Conclusions: The improved surgical technique appears to be a feasible tool for experimental and translational studies of SAH.

KEYWORDS:

• Subarachnoid haemorrhage
• early brain injury
• filament model
• translational research

Acknowledgements

The authors wish to thank radiologist Yu Guo from Army Medical University for the help of MRI scanning and data analysis; thank Yan Ding from the Center for Neuroscience Research of Loma Linda University for critical appraisal of the manuscript.

Conflict of Interest

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81771278, 81801176]; Technology Innovation Talent Project of Sichuan Province [2018RZ0090]; Health and Family Planning Commision Project of Sichuan Province [18ZD021]; Luzhou Science and Technology Board Project [2016LZXNYD-Z02, 2017-R-74].