Substantial Reduction of Parenchymal Cerebral Blood Flow in Mice with Bilateral Common Carotid Artery Stenosis

Hattori, Yorito; Enmi, Jun-ichiro; Iguchi, Satoshi; Saitô, Satoshi; Yamamoto, Yorihiro; Nagatsuka, Kazuyuki; Iida, Hidehiro; Ihara, Masafumi

doi:10.1038/srep32179

Cited by 46 publications

(51 citation statements)

References 19 publications

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“…This study also demonstrated that CBF assessed by arterial spin-labeled perfusion-magnetic resonance imaging (ASL-MRI) was correlated with FDG-PET measurements in patients with AD. Similarly, ASL-MRI methods in the BCAS mouse model showed subcortical CBF reduction over at least a 30-days period after BCAS (29). Our preliminary ASL data also showed that prolonged reduction of CBF in BCAS model was sustained over longer period of 16 weeks.…”

Section: Discussionsupporting

confidence: 72%

Brain‐derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer’s disease

et al. 2019

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Vascular factors that reduce blood flow to the brain are involved in apparition and progression of dementia. We hypothesized that cerebral hypoperfusion (CH) might alter the molecular compositions of brain intercellular communication mechanisms while affecting the neurovascular unit in preclinical and clinical human dementias. To test that hypothesis, mice were subjected to bilateral common carotid stenosis (BCAS) and the molecular compositions of brain-derived and circulating extracellular vesicles (EVs) were assessed. Murine brain vesicle profiles were then analyzed in parallel with brain EVs from post-mortem subjects affected by preclinical Alzheimer's Disease (AD) and mixed dementias. Brain EVs were identified with molecular mediators of hypoxia responses, neuroprotection and neurotoxicity in BCAS mice, patterns also partially resembled by subjects with preclinical AD and mixed dementias. Together these findings indicate that brain EVs represent a promising source of therapeutic targets and circulating markers of neurovascular insult in idiopathic dementias. Furthermore, the results obtained generate novel and compelling hypotheses about the molecular involvement of the vascular component in the etiology of human dementias.

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Section: Discussionsupporting

confidence: 72%

Brain‐derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer’s disease

et al. 2019

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“…However, a maximum reduction of CBF to approximately 50% of baseline occurred within 2 hours post-surgery, followed by a progressive recovery of CBF to approximately 80% of baseline by day 30 (Shibata et al, 2004). Also, a similar acute reduction of CBF to ~50% of baseline was observed on the first day in other studies (Kitamura, et al, 2016; Srinivasan et al, 2015; Hattori et al, 2016). Growth of collateral vessels occurs only after a few days of hypoperfusion resulting in a recovery of CBF over time (Srinivasan et al, 2015).…”

Section: Discussionsupporting

confidence: 87%

Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

Quintana

Ren

et al. 2018

Metab Brain Dis

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Chronic cerebrovascular hypoperfusion results in vascular dementia and increases predisposition to lacunar infarcts. However, there are no suitable animal models. In this study, we developed a novel model for chronic irreversible cerebral hypoperfusion in mice. Briefly, an ameroid constrictor was placed on the right carotid artery to gradually occlude the vessel, while a microcoil was placed on the left carotid artery to prevent compensation of the blood flow. This procedure resulted in a gradual hypoperfusion developing over a period of 34 days with no cerebral blood flow recovery. Histological analysis of the brain revealed neuronal and axonal degeneration as well as necrotic lesions. The most severely affected regions were located in the hippocampus and the corpus callosum. Overall, our paradigm is a viable model to study brain pathology resulting from gradual cerebrovascular hypoperfusion.

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“…) by reducing blood flow in both cortical and subcortical structures over a sustained period (Hattori et al . ). The BCAS model shares several pathological consequences with cerebral SVD including microinfarcts, microhaemorrhages and WM disruption (Holland et al .…”

Section: Contribution Of Laboratory Animal Studiesmentioning

confidence: 97%

“…The original BCAS experimental model ) established in mice is most relevant to produce cerebral hypoperfusion (Tomimoto et al 2003) by reducing blood flow in both cortical and subcortical structures over a sustained period (Hattori et al 2016a). The BCAS model shares several pathological consequences with cerebral SVD including microinfarcts, microhaemorrhages and WM Fig.…”

Section: Contribution Of Laboratory Animal Studiesmentioning

confidence: 99%

White matter degeneration in vascular and other ageing‐related dementias

Hase

Horsburgh

Ihara

et al. 2018

Journal of Neurochemistry

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168

152

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Advances in neuroimaging have enabled greater understanding of the progression of cerebral degenerative processes associated with ageing-related dementias. Leukoaraiosis or rarefied white matter (WM) originally described on computed tomography is one of the most prominent changes which occurs in older age. White matter hyperintensities (WMH) evident on magnetic resonance imaging have become commonplace to describe WM changes in relation to cognitive dysfunction, types of stroke injury, cerebral small vessel disease and neurodegenerative disorders including Alzheimer's disease. Substrates of WM degeneration collectively include myelin loss, axonal abnormalities, arteriolosclerosis and parenchymal changes resulting from lacunar infarcts, microinfarcts, microbleeds and perivascular spacing. WM cells incorporating astrocytes, oligodendrocytes, pericytes and microglia are recognized as key cellular components of the gliovascular unit. They respond to ongoing pathological processes in different ways leading to disruption of the gliovascular unit. The most robust alterations involve oligodendrocyte loss and astrocytic clasmatodendrosis with displacement of the water channel protein, aquaporin 4. These modifications likely precede arteriolosclerosis and capillary degeneration and involve tissue oedema, breach of the blood-brain barrier and induction of a chronic hypoxic state in the deep WM. Several pathophysiological mechanisms are proposed to explain how WM changes commencing with haemodynamic changes within the vascular system impact on cognitive dysfunction. Animal models simulating cerebral hypoperfusion in man have paved the way for several translational opportunities. Various compounds with variable efficacies have been tested to reduce oxidative stress, inflammation and blood-brain barrier damage in the WM. Our review demonstrates that WM degeneration encompasses multiple substrates and therefore more than one pharmacological approach is necessary to preserve axonal function and prevent cognitive impairment. Keywords: astrocytes, blood-brain barrier, post-stroke dementia, stroke, vascular dementia, white matter. Ageing-related cognitive impairment involves multiple substrates affecting brain structure and function. Neuroimaging evidence shows that white matter (WM) changes are associated with various clinical, sensorimotor, lifestyle, behavioural and cognitive abnormalities, particularly related to the small vessel disease (SVD) syndrome (Pantoni 2010).

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Substantial Reduction of Parenchymal Cerebral Blood Flow in Mice with Bilateral Common Carotid Artery Stenosis

Cited by 46 publications

References 19 publications

Brain‐derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer’s disease

Brain‐derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer’s disease

Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

White matter degeneration in vascular and other ageing‐related dementias

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