Vasa vasorum formation is associated with rupture of intracranial aneurysms

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  • 1 Department of Molecular Pharmacology, Research Institute, and
  • 2 Core Research for Evolutional Science and Technology (CREST) from the Japanese Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka;
  • 3 Department of Neurosurgery, Shiga University of Medical Science, Shiga;
  • 4 Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto;
  • 5 Department of Neurosurgery, Tokyo Women’s Medical University Medical Center East, Tokyo;
  • 6 Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto;
  • 7 Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo; and
  • 8 Alliance Laboratory for Advanced Medical Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
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OBJECTIVE

Subarachnoid hemorrhage (SAH) has a poor outcome despite modern advancements in medical care. The development of a novel therapeutic strategy to prevent rupture of intracranial aneurysms (IAs) or a novel diagnostic marker to predict rupture-prone lesions is thus mandatory. Therefore, in the present study, the authors established a rat model in which IAs spontaneously rupture and examined this model to clarify histopathological features associated with rupture of lesions.

METHODS

Female Sprague Dawley rats were subjected to bilateral ovariectomy; the ligation of the left common carotid, the right external carotid, and the right pterygopalatine arteries; induced systemic hypertension; and the administration of a lysyl oxidase inhibitor.

RESULTS

Aneurysmal SAH occurred in one-third of manipulated animals and the locations of ruptured IAs were exclusively at a posterior or anterior communicating artery (PCoA/ACoA). Histopathological examination using ruptured IAs, rupture-prone IAs induced at a PCoA or ACoA, and IAs induced at an anterior cerebral artery–olfactory artery bifurcation that never ruptured revealed the formation of vasa vasorum as an event associated with rupture of IAs.

CONCLUSIONS

The authors propose the contribution of a structural change in an adventitia, i.e., vasa vasorum formation, to the rupture of IAs. Findings from this study provide important insights about the pathogenesis of IAs.

ABBREVIATIONS ACA = anterior cerebral artery; ACoA = anterior communicating artery; BA = basilar artery; CCA = common carotid artery; ECA = external carotid artery; EVG = elastica van Gieson; FOV = field of view; IA = intracranial aneurysm; ICA = internal carotid artery; IEL = internal elastic lamina; MPO = myeloperoxidase; MRA = MR angiography; OA = olfactory artery; OVX = ovariectomy; PCoA = posterior communicating artery; RT-PCR = real-time polymerase chain reaction; SAH = subarachnoid hemorrhage; SD = Sprague Dawley; SMA = smooth muscle actin.

Supplementary Materials

    • Supplemental Figures 1-12 (PDF 9.46 MB)

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Contributor Notes

Correspondence Tomohiro Aoki: National Cerebral and Cardiovascular Center, Osaka, Japan. tomoaoki@ncvc.go.jp.

INCLUDE WHEN CITING Published online August 16, 2019; DOI: 10.3171/2019.5.JNS19405.

Disclosures This work was supported in part by special coordination funds from the Ministry of Education, Culture, Sports, Science and Technology of Japan and from Astellas Pharma Inc., in the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas (Dr. Aoki); by CREST on Mechanobiology from the Japan AMED (grant no. JP18gm0810006, Dr. Aoki); and by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (no. 16K10719, Dr. Aoki).

Dr. Narumiya is supported (as was Dr. Aoki until March 31, 2017) by the coordination fund from the Japanese Ministry for Education, Culture, Sports, Science and Technology of Japan and Astellas Pharma Inc., to Kyoto University, and is a scientific advisor to Astellas Pharma.

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