Unique Remodeling Processes after Vascular Injury in Intracranial Arteries: Analysis Using a Novel Mouse Model

Shimamura, Munehisa; Nakagami, Hironori; Sata, Masataka; Takaoka, Minoru; Azuma, Junya; Osako, Mariana Kiomy; Kuroda, Hiroshi; Kurinami, Hitomi; Wakayama, Kouji; Miyake, Takashi; Morishita, Ryuichi

doi:10.1038/jcbfm.2013.62

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…Like human cerebral arteries, mouse cerebral arteries lack an external elastic lamina . Human intracranial aneurysms are characterized by destruction of the internal elastic lamina, which is either absent completely or exists as fragmentary remnants .…”

Section: Similarity Between Mouse Model and Human Intracranial Aneurysmsmentioning

confidence: 99%

Mouse Models of Intracranial Aneurysm

et al. 2014

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Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β-estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients.

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Section: Similarity Between Mouse Model and Human Intracranial Aneurysmsmentioning

confidence: 99%

Mouse Models of Intracranial Aneurysm

et al. 2014

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“…Compared with the remodelling in the femoral artery, intracranial internal carotid arteries showed a unique remodelling pattern. The formation of neointima was delayed and showed continuous macrophage accumulation, loss of SMCs followed by medial thinning and continuous expansion of the adventitia [169]. These findings suggest that pathophysiological differences exist in different peripheral arteries which are probably controlled by different genetic and epigenetic pathways.…”

Section: Smc Differentiationmentioning

confidence: 86%

“…This negative effect of an epigenetic modifying drug suggests that specific drugs have to be identified for each cell phenotype involved in the disease process. Recently, a study compared the remodelling process in the femoral and internal carotid arteries within a novel mouse vascular injury model [169]. Compared with the remodelling in the femoral artery, intracranial internal carotid arteries showed a unique remodelling pattern.…”

Section: Smc Differentiationmentioning

confidence: 99%

The relevance of epigenetics to occlusive cerebral and peripheral arterial disease

2015

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Athero-thrombosis of the arteries supplying the brain and lower limb are the main causes of stroke and limb loss. New therapies are needed to improve the outcomes of athero-thrombosis. Recent evidence suggests a role for epigenetic changes in the development and progression of ischaemic injury due to atherosclerotic occlusion of peripheral arteries. DNA hypermethylation have been associated with cardiovascular diseases. Histone post-translational modifications have also been implicated in atherosclerosis. Oxidized low-density lipoprotein regulated pro-inflammatory gene expression within endothelial cells is controlled by phosphorylation/acetylation of histone H3 and acetylation of histone H4 for example. There are a number of challenges in translating the growing evidence implicating epigenetics in atherosclerosis to improved therapies for patients. These include the small therapeutic window in conditions such as acute stroke and critical limb ischaemia, since interventions introduced in such patients need to act rapidly and be safe in elderly patients with many co-morbidities. Pre-clinical animal experiments have also reported conflicting effects of some novel epigenetic drugs, which suggest that further in-depth studies are required to better understand their efficacy in resolving ischaemic injury. Effective ways of dealing with these challenges are needed before epigenetic approaches to therapy can be introduced into practice.

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“…1 There are a number of mouse models of the physiologic or pathologic remodeling of cerebral arteries. [2][3][4][5] To study the remodeling of cerebral arteries, a noninvasive, serial imaging technique that can visualize the cerebral arteries is an extremely useful tool.…”

Section: Introductionmentioning

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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Unique Remodeling Processes after Vascular Injury in Intracranial Arteries: Analysis Using a Novel Mouse Model

Cited by 6 publications

References 25 publications

Mouse Models of Intracranial Aneurysm

Mouse Models of Intracranial Aneurysm

The relevance of epigenetics to occlusive cerebral and peripheral arterial disease

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

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