Disease Highlights the Cellular Diversity of Neurovascular Units

Faraci, Frank M.

doi:10.1161/circresaha.117.311386

Cited by 4 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other forms of brain injury, microbleeds are known to be toxic to astrocytes, neurons, and endothelial cells ( Lok et al, 2011 ) and are frequently observed surrounded by macrophages, which can initiate inflammatory and neurodegenerative cascades. Recent results show that perivascular macrophages (PVM) expressing CD36 and Nox2 are a major source of reactive oxygen species in mice overexpressing the Swedish mutation of the APP (Tg2576) and have been proposed as a therapeutic target in AD models ( Park et al, 2017 ; Faraci, 2017 ). Persistent inflammation triggered by microbleeds and platelets accumulation after TBI might be responsible for the secondary activation of microglia, stimulation of gliosis, late complement activation and apoptosis, all processes closely associated with AD and dementia ( Danaila et al, 2013 ; Kniewallner et al, 2016 ).…”

Section: Cerebrovascular Inflammation In Tbi and Admentioning

confidence: 99%

Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link

et al. 2018

View full text Add to dashboard Cite

Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post concussive syndrome, dementia and chronic traumatic encephalopathy (CTE). In addition to debilitating acute effects, TBI-induced neurovascular injuries accelerate amyloid β (Aβ) production and perivascular accumulation, arterial stiffness, tau hyperphosphorylation and tau/Aβ-induced blood brain barrier damage, giving rise to a deleterious feed-forward loop. We postulate that TBI can initiate cerebrovascular pathology, which is causally involved in the development of multiple forms of neurodegeneration including AD-like dementias. In this review, we will explore how novel biomarkers, animal and human studies with a focus on cerebrovascular dysfunction are contributing to the understanding of the consequences of TBI on the development of AD-like pathology.

show abstract

Section: Cerebrovascular Inflammation In Tbi and Admentioning

confidence: 99%

Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link

et al. 2018

View full text Add to dashboard Cite

show abstract

“… 519 In addition, PVMs also participate in Aβ induced neurovascular dysfunction through CD36 mediated oxidative stress, leading the infiltration of immune cells. 520 , 521 Single-nucleus RNA sequencing analysis suggested that PVMs from patients with AD displayed abnormity in phagocytosis, endocytosis, and interferon-γ signaling. 522 However, the mechanism of PVMs in the development of AD is still far from being elucidated.…”

Section: Signaling Pathways That Can Induce Inflammation In the Cnsmentioning

confidence: 99%

Role of neuroinflammation in neurodegeneration development

Zhang

Xiao

Mao

et al. 2023

Sig Transduct Target Ther

180

View full text Add to dashboard Cite

Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s disease, and so on, have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process. Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration. Actually, inflammation even happens earlier than protein aggregation. Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population. Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration, although they are still far from being completely understood. Due to the limited success of traditional treatment methods, blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases, and many of them have got exciting results in animal models or clinical trials. Some of them, although very few, have been approved by FDA for clinical usage. Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis. We also summarize the current strategies, both in animal models and in the clinic, for the treatment of neurodegenerative diseases.

show abstract

“…Concerning AD, the most common form of dementia in the elderly, more information exists about the vascular alterations that occur in this disease ( Gallart-Palau et al, 2016 ). Several clinical and basic evidence points to the existence of a major contribution of both large artery and small vessel disease in the pathogenesis of AD ( Iadecola, 2013 ; De Strooper and Karran, 2016 ; Faraci, 2017 ). Having this into account, the two-hit vascular hypothesis of AD emerged, postulating that cerebrovascular damage is an initial insult that is self-sufficient to initiate neuronal injury and neurodegeneration, but can also promote accumulation of Aβ peptide, a neurotoxic peptide, in the brain ( Nelson et al, 2016 ).…”

Section: Cerebrovascular Oxidative Stress and Neurodegenerative Eventmentioning

confidence: 99%

Oxidative Stress: A Major Player in Cerebrovascular Alterations Associated to Neurodegenerative Events

2018

View full text Add to dashboard Cite

The brain is one of the most exquisite organs in the body with high metabolic demands, and requires a tight regulation of the surrounding environment. This tight control is exerted by the neurovascular unit (NVU) comprising different cell types, where endothelial cells play the commander-in-chief role. Thus, it is assumable that even slight perturbations in NVU might affect, in some cases irreversibly, brain homeostasis and health. In this line, recent findings support the two-hit vascular hypothesis for neurodegenerative conditions, where vascular dysfunction underlies the development of neurodegenerative diseases, such as Alzheimer’s disease (AD). Knowing that endothelial cells are rich in mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, two major reactive oxygen species (ROS) sources, this review aims to gather information on how oxidative stress is in the front line of vascular alterations observed in brain aging and neurodegenerative conditions, particularly AD. Also, a brief discussion about the therapeutic strategies aimed to protect against cerebrovascular diseases is included.

show abstract

Disease Highlights the Cellular Diversity of Neurovascular Units

Cited by 4 publications

References 15 publications

Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link

Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link

Role of neuroinflammation in neurodegeneration development

Oxidative Stress: A Major Player in Cerebrovascular Alterations Associated to Neurodegenerative Events

Contact Info

Product

Resources

About