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Journal of Neurosurgical Sciences 2020 Feb 04

DOI: 10.23736/S0390-5616.19.04819-7


language: English

Induction of large cerebral aneurysms by intraperitoneal administration of β-aminopropionitrile fumarate in male rats

Yusuke SHIMODA, Naoki NAKAYAMA , Takuya MORIWAKI, Takeo ABUMIYA, Masahito KAWABORI, Kota KURISU, Masayuki GEKKA, Masaaki HOKARI, Yasuhiro ITO, Kiyohiro HOUKIN

Department of Neurosurgery, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, Japan


BACKGROUND: It is necessary and useful to obtain an experimental model which steadily and rapidly induces aneurysms for investigation of the pathogenesis of cerebral aneurysm. We attempted to examine whether intraperitoneal administration of β-aminopropionitrile fumarate (BAPN-F) with additional treatments of induced hypertension and hemodynamic stress could steadily and rapidly induce aneurysms in male rats.
METHODS: Seven-week-old male Sprague-Dawley rats pretreated with ligation of left common carotid and bilateral posterior renal arteries were administrated BAPN-F intraperitoneally. Induction rate and size of aneurysms was investigated with varying dose and duration of BAPN-F administration (low dose; 400 mg/kg/week for 4 or 8 weeks and high dose; 2800 mg/kg/week for 8 or 12 weeks).
RESULTS: Induction rate in the high-dose groups was significantly higher (p<0.01) than that in the low-dose groups. Making comparisons between 8 and 12 weeks of the high-dose groups, while there was no difference in induction rate (8 weeks; 85.2% vs 12 weeks; 76.9%), aneurysmal size was larger in 12 weeks (8 weeks; 127.5 μm, vs 12 weeks; 181.7 μm in terms of median) but lethal intrathoracic hemorrhage was increased in 12 weeks (8 weeks; 7.4% vs 12 weeks; 30.8%). Induction rate of large aneurysm was 22.2% and 30.8% in 8 and 12 weeks of the high-dose groups, respectively.
CONCLUSIONS: High-dose BAPN-F administration can cause high-frequency aneurysmal induction. Although there was the difference in size and mortality rate based on administration duration, intraperitoneal administration of 2800 mg/kg/week BAPN-F for 8 weeks would be suitable for aneurysmal induction.

KEY WORDS: Beta-aminopropionitrile fumarate; Intraperitoneal administration; Cerebral aneurysm; Rat model

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