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Optimisation of the MCA perforation model for the induction of subarachnoid haemorrhage in mice allows long-term studies
Optimierung des A. cerebri media Perforations-Modells für die Induktion einer Subarachnoidalblutung bei der Maus erlaubt Langzeit-Studien
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Veröffentlicht: | 4. Juni 2021 |
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Objective: Middle cerebral artery (MCA) filament perforation is a standard technique to model aneurysmatic subarachnoid hemorrhage (SAH). To quantify hemorrhage induction and distinguish SAH from focal cerebral ischemia (i.e. MCA occlusion without perforation), intracranial pressure (ICP) and cerebral blood flow (CBF) monitoring are mandatory. For this, an ICP sensor needs to be placed intraparenchymally/epidurally while CBF is measured over the ipsilateral (iCBF) or contralateral (cCBF) MCA territory. Due to its size, which for technical reasons cannot be further miniaturized an ICP sensor induces some inevitable brain tissue injury and may thus significantly alter long-term SAH pathology. We therefore assessed whether also bilateral CBF measurements may be suitable to detect SAH in mice thereby allowing long-term experiments.
Methods: Tissue damage caused by probe placement was assessed in C57Bl/6 mice (n=3) by T2 weighted MRI scans performed 7 and 14d after ICP-probe placement. To assess whether correct SAH induction can be monitored by CBF measurements alone, MCA perforation or sham surgery (n=7) was performed in C57BL/6 mice under bilateral CBF measurement by laser doppler flowmetry with (n=25) or without (n=9) additional epidural ICP measurement. We then determined maximum ICP, minimum CBF, hemorrhage volume at the skull base, and assessed histological brain damage in all groups.
Results: T2-imaging in mice after ICP probe placement showed edema formation and persistant cortical damage after 7 (14.7 ±11.7mm3) and 14 days (11.8 ±1.4mm3); p=0.6. Bilateral CBF and ICP measurements revealed a temporal correlation of ICP maximum and cCBF minimum: ICP vs. cCBF: r=0,5, p=0,01; ICP vs. iCBF r=0,7, p < 0,01. ICP and cCBF showed also a correlation of absolute extreme values: r=0,5, p=0,02. ICP clot volume and histopathological damage were comparable in both groups.
Conclusion: Although ICP measurement is the most reliable parameter for detecting SAH induction by MCA perforation, it is critical in the context of long-term experiments as it induces a progressive tissue lesion which may confound results. Bilateral CBF measurements correlate with ICP findings and allow ascertaining correct MCA perforation/SAH induction. We therefore conclude that monitoring by bilateral CBF measurement alone is safe and effective for long-term experiments using the MCA perforation model in mice.