Roles of Hypertension in the Rupture of Intracranial Aneurysms

Tada, Yasuyuki; Wada, Kodai; Shimada, Kenji; Makino, Hiroshi; Liang, Elena I.; Murakami, Shoko; Kudo, Mari; Kitazato, Keiko T.; Saijo, Nagahiro; Hashimoto, Tomoki

doi:10.1161/strokeaha.113.003072

Cited by 141 publications

(134 citation statements)

References 31 publications

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“…16,24 More importantly, human intracranial aneurysms and aneurysms in this model share the common end phenotype, i.e., aneurysmal rupture and associated symptoms. 13,14 This model with or without modifications have been successfully used by other groups to study the mechanisms for aneurysmal formation and rupture. 3,28 Clinical studies that assess the correlation between aneurysmal rupture and the use of agents that affect the Ang-(1-7) system will be need to validate our findings.…”

Section: Discussionmentioning

confidence: 99%

“…Using the tail cuff method, systolic blood pressure was measured in the mice before aneurysm induction and every week after the elastase injection. 13,14 Real-Time PCR Analysis…”

Section: Experimental Protocolmentioning

confidence: 99%

“…We used a mouse model of intracranial aneurysms in which spontaneous aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) causes neurologic symptoms. 13,14 …”

Section: Introductionmentioning

confidence: 99%

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Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

Shimada

Furukawa

Wada

et al. 2015

J Cereb Blood Flow Metab

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Angiotensin-(1-7) (Ang-(1-7)) can regulate vascular inflammation and remodeling, which are processes that have important roles in the pathophysiology of intracranial aneurysms. In this study, we assessed the effects of Ang-(1-7) in the development of intracranial aneurysm rupture using a mouse model of intracranial aneurysms in which aneurysmal rupture (i.e., aneurysmal subarachnoid hemorrhage) occurs spontaneously and causes neurologic symptoms. Treatment with Ang-(1-7) (0.5 mg/kg/day), Mas receptor antagonist (A779 0.5 mg/kg/day or 2.5 mg/kg/day), or angiotensin II type 2 receptor (AT2R) antagonist (PD 123319, 10 mg/kg/day) was started 6 days after aneurysm induction and continued for 2 weeks. Angiotensin-(1-7) significantly reduced the rupture rate of intracranial aneurysms without affecting the overall incidence of aneurysms. The protective effect of Ang-(1-7) was blocked by the AT2R antagonist, but not by the Mas receptor antagonist. In AT2R knockout mice, the protective effect of Ang-(1-7) was absent. While AT2R mRNA was abundantly expressed in the cerebral arteries and aneurysms, Mas receptor mRNA expression was very scarce in these tissues. Angiotensin-(1-7) reduced the expression of tumor necrosis factor-α and interleukin-1β in cerebral arteries. These findings indicate that Ang-(1-7) can protect against the development of aneurysmal rupture in an AT2R-dependent manner.

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Section: Discussionmentioning

confidence: 99%

“…Using the tail cuff method, systolic blood pressure was measured in the mice before aneurysm induction and every week after the elastase injection. 13,14 Real-Time PCR Analysis…”

Section: Experimental Protocolmentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

Shimada

Furukawa

Wada

et al. 2015

J Cereb Blood Flow Metab

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“…Particularly, the role of systemic blood pressure was shown to be important in rupturing the aneurysm. In an animal study reduction of blood pressure with hydralazine correlated well with prevention of aneurysm rupture [3] . Other risk factors are history of previous aneurysm rupture and a blunt head trauma with subsequent development of cerebral aneurysms [4,5] .…”

Section: Discussionmentioning

confidence: 94%

Primary Cesarean Delivery Complicated by the Incidental Finding of a Cerebral Aneurysm: Selecting a Safe Anesthesia Technique

Chee¹,

Internationals²

2015

JAS

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The presence of a cerebral aneurysm in an obstetric patient raises a special anesthetic concern for cesarean delivery. General anesthesia poses the inherently increased risk of a difficult airway as well as an adverse impact of hypertension during induction and emergence. Epidural anesthesia may facilitate gradual hemodynamic changes and allows intraoperative neurologic monitoring. However, potential dural puncture headache may lender it difficult to recognize an intracranial hemorrhage. In the end, spinal anesthesia was chosen for the advantage of avoiding hypertensive responses from either airway stimulation or inadequate analgesia.

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“…7,9 The mice also received a single injection of elastase solution (35 milli-units Elastase: E7885, Sigma Aldrich dissolved in 2.5 μL of phosphate-buffered saline) into the cerebrospinal fluid in the right basal cistern on the same day as the DOCA pellet implantation. [6][7][8] The nephrectomy was performed under general anesthesia with 2% isoflurane. The elastase injection was performed under general anesthesia induced by an intraperitoneal injection of ketamine (100 mg/kg) and xylazine (10 mg/kg).…”

Section: The Mouse Model Of Intracranial Aneurysm and Subarachnoid Hementioning

confidence: 99%

Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

Makino

Hokamura²,

Natsume

et al. 2015

J Cereb Blood Flow Metab

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Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7 ± 0.5 minutes and 4.8 ± 0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice. 1 There are a number of mouse models of the physiologic or pathologic remodeling of cerebral arteries. Journal of Cerebral Blood2-5 To study the remodeling of cerebral arteries, a noninvasive, serial imaging technique that can visualize the cerebral arteries is an extremely useful tool.We report on the feasibility of using a readily available, conventional 3-T clinical magnetic resonance imaging (MRI) system to serially image cerebral arteries in mice. As a test case, we utilized a mouse model of an intracranial aneurysm that shows dynamic changes in the cerebral arteries. 2,6,7 In this model, intracranial aneurysms were induced by a combination of systemic hypertension and a single injection of elastase into the cerebrospinal fluid.

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Roles of Hypertension in the Rupture of Intracranial Aneurysms

Cited by 141 publications

References 31 publications

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

Primary Cesarean Delivery Complicated by the Incidental Finding of a Cerebral Aneurysm: Selecting a Safe Anesthesia Technique

Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

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