Endothelial cell–oligodendrocyte interactions in small vessel disease and aging

Rajani, Rikesh M.; Williams, Anna

doi:10.1042/cs20160618

Cited by 47 publications

(45 citation statements)

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“…Furthermore, the Austrian Stroke Prevention Study found an association between intercellular adhesion molecule levels and WMH progression at 3 and 6 years (Markus et al 2005). Overall, these studies indicate that altered endothelial cell signaling might cause oligodendrocytes to be more vulnerable to damage, either by reducing their exposure to pro-survival factors or by reducing the ability of white matter to repair itself after injury (Rajani & Williams 2017 In summary, endothelial dysfunction is a pathological hallmark of SVD (Poggesi et al 2016). Immunohistological labeling shows evidence of vessel wall thickening and upregulation of hypoxia-related markers within white matter lesions (Fernando et al 2006).…”

mentioning

confidence: 88%

“…Endothelial cells can also have a direct impact on oligodendrocytes, which are derived from oligodendrocyte precursor cells (OPC) (Rajani and Williams 2017). Oligodendrocyte precursor cells arise from many different regions of the brain during development and are also present throughout the adult brain.…”

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

“…Endothelial function plays an important role in the support of OPC (Rajani & Williams 2017). Endothelial cells can secrete factors, such as fibroblast growth factor and BDNF, that promote OPC proliferation (Leventhal et al 1999).…”

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

“…This can cause platelet aggregation, white blood cell adhesion, and inflammation, which may initiate and advance vascular pathology (Rajani and Williams 2017). Dysfunctional endothelial cells secrete factors such as VEGF, tumor necrosis factor-a, and endothelin 1 that may have negative effects on other brain cells (Griendling et al 2011;Rajani and Williams 2017).…”

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

“…Oligodendrocytes are also involved in the trophic support of axons by secreting insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF) (Du and Dreyfus 2002). Thus, the proper function of oligodendrocytes is essential for brain health.Endothelial function plays an important role in the support of OPC (Rajani & Williams 2017). Endothelial cells can secrete factors, such as fibroblast growth factor and BDNF, that promote OPC proliferation (Leventhal et al 1999).…”

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confidence: 99%

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The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

Dao

Hsiung

Liu-Ambrose

2017

Journal of Neurochemistry

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Subcortical ischemic vascular cognitive impairment (SIVCI) is the most preventable form of cognitive dysfunction. There is converging evidence from animal and human studies that indicate vascular injury as the primary cause of SIVCI. Currently, there are no curative pharmaceutical treatments for vascular dementia; however, exercise may be a promising strategy to combat SIVCI. This review will focus on the role of exercise as a strategy to prevent or slow the progression of SIVCI, with particular emphasis on the mechanisms by which exercise may improve cerebrovascular function. We propose that exercise may be an effective strategy to combat SIVCI by improving cognitive function, increasing the bioavailability of neurotrophins, stimulating endothelial function, and controlling vascular risk factors. Keywords: endothelial function, exercise, subcortical ischemic vascular cognitive impairment, white matter hyperintensities. J. Neurochem. (2018) 144, 582--594.This article is part of the Special Issue "Vascular Dementia".The World Health Organization estimates that 47.5 million people worldwide are living with dementia with an expected increase of 7.7 million new cases each year (World Health Organization 2012). Dementia is a common cause of disability and dependency among older adults; thus, the high prevalence and incidence of dementia is a great burden to health, social, and financial systems (World Health Organization 2012). Vascular cognitive impairment (VCI) is the second leading cause of cognitive impairment and dementia (van Norden et al. 2012). Vascular cognitive impairment is an umbrella term that encompasses the full spectrum of cognitive and functional impairments associated with cerebrovascular disease, from frank dementia to mild cognitive deficits (Gorelick et al. 2011). Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of VCI and is caused by cerebral small vessel disease (SVD) (Moorhouse and Rockwood 2008). Cerebral SVD is caused by chronic and diffuse ischemia and is most often associated with damage to cerebral white matter. Specifically, it manifests as white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces, and microbleeds (Wardlaw et al. 2013b).Overall, there is converging evidence from animal and human studies that indicate vascular injury as the primary cause of SIVCI (Iadecola 2013). Vascular risk factors such as Received May 29, 2017; revised manuscript received August 9, 2017; accepted August 11, 2017.Address correspondence and reprint requests to Teresa Liu-Ambrose, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3. USA. E-mail: teresa.ambrose@ubc.caAbbreviations used: ADAS-Cog, Alzheimer's Disease Assessment Scale-cognitive subscale; BDNF, brain-derived neurotrophic factor; CBF, cerebral blood flow; eNOS, endothelial nitric oxide synthase; fMRI, functional magnetic resonance imaging MRI; IGF-1, insulin-like growth factor 1; MCI, mild cognitive impairment; MRI, m...

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mentioning

confidence: 88%

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

Section: The Vascular Network and Cerebral White Mattermentioning

confidence: 99%

mentioning

confidence: 99%

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The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

Dao

Hsiung

Liu-Ambrose

2017

Journal of Neurochemistry

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Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment

Askew,

Beverley,

Sigfridsson

et al. 2023

Glia

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White matter abnormalities, related to poor cerebral perfusion, are a core feature of small vessel cerebrovascular disease, and critical determinants of vascular cognitive impairment and dementia. Despite this importance there is a lack of treatment options. Proliferation of microglia producing an expanded, reactive population and associated neuroinflammatory alterations have been implicated in the onset and progression of cerebrovascular white matter disease, in patients and in animal models, suggesting that targeting microglial proliferation may exert protection. Colony‐stimulating factor‐1 receptor (CSF1R) is a key regulator of microglial proliferation. We found that the expression of CSF1R/Csf1r and other markers indicative of increased microglial abundance are significantly elevated in damaged white matter in human cerebrovascular disease and in a clinically relevant mouse model of chronic cerebral hypoperfusion and vascular cognitive impairment. Using the mouse model, we investigated long‐term pharmacological CSF1R inhibition, via GW2580, and demonstrated that the expansion of microglial numbers in chronic hypoperfused white matter is prevented. Transcriptomic analysis of hypoperfused white matter tissue showed enrichment of microglial and inflammatory gene sets, including phagocytic genes that were the predominant expression modules modified by CSF1R inhibition. Further, CSF1R inhibition attenuated hypoperfusion‐induced white matter pathology and rescued spatial learning impairments and to a lesser extent cognitive flexibility. Overall, this work suggests that inhibition of CSF1R and microglial proliferation mediates protection against chronic cerebrovascular white matter pathology and cognitive deficits. Our study nominates CSF1R as a target for the treatment of vascular cognitive disorders with broader implications for treatment of other chronic white matter diseases.

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The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment

Liu

Diao

et al. 2019

Neurol Sci

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Endothelial cell–oligodendrocyte interactions in small vessel disease and aging

Cited by 47 publications

References 116 publications

The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment

The global burden of cerebral small vessel disease related to neurological deficit severity and clinical outcomes of acute ischemic stroke after IV rt-PA treatment

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