A small animal model for early cerebral aneurysm pathology

Lee, James A., Marshman, Laurence A.G., Moran, Corey S., Kuma, Leslie, Guazzo, Eric P., Anderson, David S., and Golledge, Jonathan (2016) A small animal model for early cerebral aneurysm pathology. Journal of Clinical Neuroscience, 34. pp. 259-263.

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Abstract

Prior studies, using systemic hypertension and elastase infusion, have induced cerebral aneurysm (CA) formation in mice. However, the CAs induced were rapidly formed, relatively large, and often ruptured. These features are not completely representative of human CAs. We set out to develop a mouse model representative of the early pathological features of human CA. Twenty male C57/BL6 mice were placed in a stereotactic frame. Low dose elastase solution (2μl/min) was manually injected into the right basal cistern. Human angiotensin II (0.11μl/h) was infused subcutaneously. Mice were observed for 2-3weeks prior to euthanasia. Early CA histopathological features including endothelial change (EC) and internal elastic lamina degeneration (IELD) were systematically sought at major cerebral arterial bifurcations. Brains were harvested from 11 of 15 mice, yielding 27 bifurcations. Sub-arachnoid haemorrhage (SAH) without CA formation was observed in one brain. Macroscopic CA without SAH was observed in another brain. Early CA features were observed in 8/11 (73%) brains. All bifurcations with IELD demonstrated EC: where EC was absent, IELD was also absent. EC severity appeared to correlate with IELD severity. EC and IELD were both severe within the CA. Using lower dose elastase solution than previously employed, we developed a model of early CA pathology. Our model demonstrated that the spectrum of known early CA pathology can be created at multiple bifurcations in mice, with EC severity appearing to correlate with IELD severity. This model permits the study of factors which potentially advance or retard the progression of CA formation.

Item ID: 47108
Item Type: Article (Research - C1)
ISSN: 1532-2653
Keywords: cerebral aneurysm, elastase, murine, small animal, stereotactic
Funders: Australian National Health and Medical Research Council (NHMRC), Queensland Government
Projects and Grants: NHMRC 1079193, 1079369, 1021416 & 1000967
Date Deposited: 04 Jan 2017 08:03
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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