Time-dependent and site-dependent morphological changes in rupture-prone arteries: ovariectomized rat intracranial aneurysm model

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  • Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
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OBJECTIVE

The pathogenesis of intracranial aneurysm rupture remains unclear. Because it is difficult to study the time course of human aneurysms and most unruptured aneurysms are stable, animal models are used to investigate the characteristics of intracranial aneurysms. The authors have newly established a rat intracranial aneurysm rupture model that features site-specific ruptured and unruptured aneurysms. In the present study the authors examined the time course of changes in the vascular morphology to clarify the mechanisms leading to rupture.

METHODS

Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic changes, hypertension, and ovariectomy. Morphological changes in rupture-prone intracranial arteries were examined under a scanning electron microscope and the association with vascular degradation molecules was investigated.

RESULTS

At 2–6 weeks after aneurysm induction, morphological changes and rupture were mainly observed at the posterior cerebral artery; at 7–12 weeks they were seen at the anterior Willis circle including the anterior communicating artery. No aneurysms at the anterior cerebral artery–olfactory artery bifurcation ruptured, suggesting that the inception of morphological changes is site dependent. On week 6, the messenger RNA level of matrix metalloproteinase–9, interleukin-1β, and the ratio of matrix metalloproteinase–9 to the tissue inhibitor of metalloproteinase–2 was significantly higher at the posterior cerebral artery, but not at the anterior communicating artery, of rats with aneurysms than in sham-operated rats. These findings suggest that aneurysm rupture is attributable to significant morphological changes and an increase in degradation molecules.

CONCLUSIONS

Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysms to rupture.

ABBREVIATIONS ACA-OlfA = anterior cerebral artery–olfactory artery; ACoA = anterior communicating artery; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; IL-1β = interleukin-1β; MMP-9 = matrix metalloproteinase–9; mRNA = messenger RNA; OVX = ovariectomy; PCA = posterior cerebral artery; qRT-PCR = quantitative reverse transcription polymerase chain reaction; SAH = subarachnoid hemorrhage; SEM = scanning electron microscope; TIMP2 = tissue inhibitor of metalloproteinase–2.

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Contributor Notes

Correspondence Tadashi Yamaguchi: Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan. tadashi117117@hotmail.co.jp.

INCLUDE WHEN CITING Published online September 13, 2019; DOI: 10.3171/2019.6.JNS19777.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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