Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect

Cai, Wei; Zhang, Kai; Li, Peiying; Zhu, Ling; Xu, Jing; Yang, Boyu; Hu, Xiaoming; Lu, Zhengqi; Chen, Jun

doi:10.1016/j.arr.2016.09.006

Cited by 212 publications

(178 citation statements)

References 133 publications

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“…Also, the neurovascular unit, which is the functional unit of the BBB, is composed of the cerebral microvascular endothelium together with pericytes, the endfeet of astrocytes, adjacent neurons, and basal lamina . An increasing body of evidence suggests that alterations in neuron–glial interactions and dysfunction of the neurovascular unit are associated with neurodegenerative diseases including Alzheimer's disease and Parkinson's disease . For instance, recently, researchers have identified leakage in the BBB in early AD patients with the decreased expression of tight junction proteins and disruption of the BBB clearance system which seems to increase the risk of AD .…”

Section: Microfluidic Cell Culture Systemsmentioning

confidence: 99%

In Vitro Microfluidic Models for Neurodegenerative Disorders

Osaki

Shin

Sivathanu

et al. 2017

Adv Healthcare Materials

107

112

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Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps.

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Section: Microfluidic Cell Culture Systemsmentioning

confidence: 99%

In Vitro Microfluidic Models for Neurodegenerative Disorders

Osaki

Shin

Sivathanu

et al. 2017

Adv Healthcare Materials

107

112

View full text Add to dashboard Cite

show abstract

“…during transient or permanent vascular obstruction, all the functions and molecules in the neurons, glial cells (oligodendrocytes, microglia and astrocytes) and vascular cells (endothelial cells and pericytes), identified as components of the neurovascular unit, are affected (9). dangerous molecular signals are released from the damaged cells following multiple types of cellular stress (10). These signals, including danger signals denominated damage-associated molecular patterns (dAMPs) and pathogen-associated molecular patterns (PAMPs), activate the innate immune system via intracellular and extracellular pattern recognition receptors (PRRs), which have been highlighted recently as an important inflammatory mechanism that may contribute to cerebral ischemic injury (11).…”

Section: Introductionmentioning

confidence: 99%

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review)

Liu

Zhang

et al. 2018

Int J Mol Med

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“…The impact of other NVU components, such as astrocytes have been extensively reviewed elsewhere. 8, 9 …”

mentioning

confidence: 99%

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

et al. 2017

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The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

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Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect

Cited by 212 publications

References 133 publications

In Vitro Microfluidic Models for Neurodegenerative Disorders

In Vitro Microfluidic Models for Neurodegenerative Disorders

Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review)

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

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