A Pilot Study Investigating Changes in Capillary Hemodynamics and Its Modulation by Exercise in the APP-PS1 Alzheimer Mouse Model

Lu, Xuecong; Moeini, Mohammad; Li, Baoqiang; Lu, Yuankang; Damseh, Rafat; Pouliot, Philippe; Thorin, Éric; Lesage, Frédéric

doi:10.3389/fnins.2019.01261

Cited by 15 publications

(22 citation statements)

References 55 publications

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“…In contrast, the mean capillary RBC velocities were within the scopes of 0.1∼1.6 mm/s and 0.05∼0.9 mm/s as reported by Emmanuelle (Chaigneau et al, 2003) and Stefanovic et al (2008). In some other studies, the velocities in both anesthetized and awake mice were calculated to be approximately 0.7 or 1.3 mm/s (Huang et al, 2014;Wei et al, 2016;Li et al, 2019;Lu et al, 2019). Comparing to these values, our data seemed to be lower.…”

Section: Discussionsupporting

confidence: 52%

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In vivo Two-Photon Imaging Reveals Acute Cerebral Vascular Spasm and Microthrombosis After Mild Traumatic Brain Injury in Mice

et al. 2020

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Mild traumatic brain injury (mTBI), or concussion, is reported to interfere with cerebral blood flow and microcirculation in patients, but our current understanding is quite limited and the results are often controversial. Here we used longitudinal in vivo twophoton imaging to investigate dynamic changes in cerebral vessels and velocities of red blood cells (RBC) following mTBI. Closed-head mTBI induced using a controlled cortical impact device resulted in a significant reduction of dwell time in a Rotarod test but no significant change in water maze test. Cerebral blood vessels were repeatedly imaged through a thinned skull window at baseline, 0.5, 1, 6 h, and 1 day following mTBI. In both arterioles and capillaries, their diameters and RBC velocities were significantly decreased at 0.5, 1, and 6 h after injury, and recovered in 1 day post-mTBI. In contrast, decreases in the diameter and RBC velocity of venules occurred only in 0.5-1 h after mTBI. We also observed formation and clearance of transient microthrombi in capillaries within 1 h post-mTBI. We concluded that in vivo two-photon imaging is useful for studying earlier alteration of vascular dynamics after mTBI and that mTBI induced reduction of cerebral blood flow, vasospasm, and formation of microthrombi in the acute stage following injury. These changes may contribute to early brain functional deficits of mTBI.

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Section: Discussionsupporting

confidence: 52%

“…Comparing to these values, our data seemed to be lower. One possible reason may be due to the relatively smaller capillaries (with a mean diameter of 3.96 µm) we imaged than those imaged in prior studies (with mean diameters of 4.7 to 6 µm) (Li et al, 2019;Lu et al, 2019). Small vessels usually have lower RBC velocity.…”

Section: Discussionmentioning

confidence: 77%

In vivo Two-Photon Imaging Reveals Acute Cerebral Vascular Spasm and Microthrombosis After Mild Traumatic Brain Injury in Mice

et al. 2020

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“…Penetrating vessels have a tortuous shape, with a tendency to decrease in diameter with aging in AD (Dorr et al, 2012 ). Capillaries been reported to increase (trending) in diameter in APP/PS1 mice (Lu et al, 2019 ), experience swelling in APP23 mice (Meyer et al, 2008 ), decrease in diameter in P301L tau mice (Bennett et al, 2018 ), and to form “string” vessels with no flow or blood cells in humans (Hunter et al, 2012 ). Tissue undergoes atrophy, causing vascular shrinkage and functional brain deficits such as memory loss.…”

Section: Vasculature In Alzheimer's Diseasementioning

confidence: 99%

Microvascular Alterations in Alzheimer's Disease

Steinman

Sun

Feng

2021

Front. Cell. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disorder associated with continual decline in cognition and ability to perform routine functions such as remembering familiar places or understanding speech. For decades, amyloid beta (Aβ) was viewed as the driver of AD, triggering neurodegenerative processes such as inflammation and formation of neurofibrillary tangles (NFTs). This approach has not yielded therapeutics that cure the disease or significant improvements in long-term cognition through removal of plaques and Aβ oligomers. Some researchers propose alternate mechanisms that drive AD or act in conjunction with amyloid to promote neurodegeneration. This review summarizes the status of AD research and examines research directions including and beyond Aβ, such as tau, inflammation, and protein clearance mechanisms. The effect of aging on microvasculature is highlighted, including its contribution to reduced blood flow that impairs cognition. Microvascular alterations observed in AD are outlined, emphasizing imaging studies of capillary malfunction. The review concludes with a discussion of two therapies to protect tissue without directly targeting Aβ for removal: (1) administration of growth factors to promote vascular recovery in AD; (2) inhibiting activity of a calcium-permeable ion channels to reduce microglial activation and restore cerebral vascular function.

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“…Mouse models of familial AD exhibit differences depending on the specific mutations and transgenes they carry. However, many present vascular alterations (Iadecola, 2017), including altered cerebral perfusion (Hebert et al, 2013;Guo et al, 2019), impaired NVC (Badhwar et al, 2013;Lu et al, 2019), capillary endothelial degeneration, thickening (Zlokovic, 2005), and loss of pericytes and BBB integrity (Sagare et al, 2013;Montagne et al, 2020), before behavioral changes and deposition of amyloid plaques. As in humans, these observations support the notion that vascular dysfunction is an essential factor in the onset of cognitive decline.…”

Section: Vascular Contributors To Cognitive Impairment and Dementiamentioning

confidence: 99%

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

et al. 2020

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Components of the neurovascular unit (NVU) establish dynamic crosstalk that regulates cerebral blood flow and maintain brain homeostasis. Here, we describe accumulating evidence for cellular elements of the NVU contributing to critical physiological processes such as cerebral autoregulation, neurovascular coupling, and vasculoneuronal coupling. We discuss how alterations in the cellular mechanisms governing NVU homeostasis can lead to pathological changes in which vascular endothelial and smooth muscle cell, pericyte and astrocyte function may play a key role. Because hypertension is a modifiable risk factor for stroke and accelerated cognitive decline in aging, we focus on hypertension-associated changes on cerebral arteriole function and structure, and the molecular mechanisms through which these may contribute to cognitive decline. We gather recent emerging evidence concerning cognitive loss in hypertension and the link with vascular dementia and Alzheimer's disease. Collectively, we summarize how vascular dysfunction, chronic hypoperfusion, oxidative stress, and inflammatory processes can uncouple communication at the NVU impairing cerebral perfusion and contributing to neurodegeneration.

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A Pilot Study Investigating Changes in Capillary Hemodynamics and Its Modulation by Exercise in the APP-PS1 Alzheimer Mouse Model

Cited by 15 publications

References 55 publications

In vivo Two-Photon Imaging Reveals Acute Cerebral Vascular Spasm and Microthrombosis After Mild Traumatic Brain Injury in Mice

In vivo Two-Photon Imaging Reveals Acute Cerebral Vascular Spasm and Microthrombosis After Mild Traumatic Brain Injury in Mice

Microvascular Alterations in Alzheimer's Disease

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension

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