title: A small animal model for early cerebral aneurysm pathology.
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.
authors.affiliation: Department of Neurosurgery, The Townsville Hospital, 100 Angus Smith Drive, Douglas, Townsville, QLD 4814, Australia; Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia; School of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, The Townsville Hospital, 100 Angus Smith Drive, Douglas, Townsville, QLD 4814, Australia; School of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia. Electronic address: l.a.g.marshman@btinternet.com.
authors.forename: Laurence A G
authors.initials: LA
authors.lastname: Marshman
authors.affiliation: Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Moran
authors.affiliation: Department of Pathology, The Townsville Hospital, Douglas, Townsville, QLD, Australia.
authors.forename: Leslie
authors.initials: L
authors.lastname: Kuma
authors.affiliation: Department of Neurosurgery, The Townsville Hospital, 100 Angus Smith Drive, Douglas, Townsville, QLD 4814, Australia; School of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Guazzo
authors.affiliation: Department of Neurosurgery, The Townsville Hospital, 100 Angus Smith Drive, Douglas, Townsville, QLD 4814, Australia.
authors.forename: David S
authors.initials: DS
authors.lastname: Anderson
authors.affiliation: Department of Vascular and Endovascular Surgery, The Townsville Hospital, Douglas, Townsville, QLD, Australia; Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Douglas, Townsville, QLD, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D002532:Intracranial Aneurysm / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010196:Pancreatic Elastase
keywords: Cerebral aneurysm; Elastase; Murine; Small animal; Stereotactic