How does neurovascular unit dysfunction contribute to multiple sclerosis?

Cashion, Jake M.; Young, Karen; Sutherland, Brad A.

doi:10.1016/j.nbd.2023.106028

Cited by 20 publications

(18 citation statements)

References 287 publications

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“…127 The NVU can regulate BBB parameters according to the needs of the brain, thereby coupling neuronal activity with vascular function, controlling brain homeostasis, and maintaining the best brain microenvironment for neuronal survival. 128 Wu et al found that galangin improved neurological deficits and NVU damage after MCAO. Further investigation of the neuroprotective mechanism of galangin showed that galangin downregulated hypoxia-inducible factor-1α (HIF-1α), VEGF, Fzd1, and LRP6, reduced the phosphorylation of β-catenin (pβ-catenin), and increased the phosphorylation of Smad3, indicating that galangin can activate VEGF in a HIF-1αdependent manner, which in turn activates the Wnt pathway after acute IS.…”

Section: Natural Compounds Regulate the Wnt Signaling Pathway In Ismentioning

confidence: 99%

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

Li,

Wang,

Zhang

2024

J. Agric. Food Chem.

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As an important signaling pathway in multicellular eukaryotes, the Wnt signaling pathway participates in a variety of physiological processes. Recent studies have confirmed that the Wnt signaling pathway plays an important role in neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. The regulation of Wnt signaling by natural compounds in herbal medicines and nutraceuticals has emerged as a potential strategy for the development of new drugs for neurological disorders. Purpose: The aim of this review is to evaluate the latest research results on the efficacy of natural compounds derived from herbs and nutraceuticals in the prevention and treatment of neurological disorders by regulating the Wnt pathway in vivo and in vitro. A manual and electronic search was performed for English articles available from PubMed, Web of Science, and ScienceDirect from the January 2010 to February 2023. Keywords used for the search engines were "natural products,″ "plant derived products,″ "Wnt+ clinical trials,″ and "Wnt+,″ and/or paired with "natural products″/″plant derived products", and "neurological disorders." A total of 22 articles were enrolled in this review, and a variety of natural compounds from herbal medicine and nutritional foods have been shown to exert therapeutic effects on neurological disorders through the Wnt pathway, including curcumin, resveratrol, and querctrin, etc. These natural products possess antioxidant, anti-inflammatory, and angiogenic properties, confer neurovascular unit and blood−brain barrier integrity protection, and affect neural stem cell differentiation, synaptic formation, and neurogenesis, to play a therapeutic role in neurological disorders. In various in vivo and in vitro studies and clinical trials, these natural compounds have been shown to be safe and tolerable with few adverse effects. Natural compounds may serve a therapeutic role in neurological disorders by regulating the Wnt pathway. This summary of the research progress of natural compounds targeting the Wnt pathway may provide new insights for the treatment of neurological disorders and potential targets for the development of new drugs.

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Section: Natural Compounds Regulate the Wnt Signaling Pathway In Ismentioning

confidence: 99%

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

Li,

Wang,

Zhang

2024

J. Agric. Food Chem.

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“…For many people, relapsing-remitting MS (RRMS) precedes secondary progressive MS, in which disability gets steadily worse. MS onset has been recognized as a multifaceted interplay of genetic, environmental, and lifestyle risk factors [ 120 ]. The environmental and lifestyle risk factors for MS onset include cigarette smoking [ 121 ], youth obesity [ 122 ], and Epstein–Barr virus infection [ 123 ].…”

Section: Chitinases and Multiple Sclerosis (Ms)mentioning

confidence: 99%

Chitinase Signature in the Plasticity of Neurodegenerative Diseases

Russo

Valle

Casabona

et al. 2023

IJMS

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Several reports have pointed out that Chitinases are expressed and secreted by various cell types of central nervous system (CNS), including activated microglia and astrocytes. These cells play a key role in neuroinflammation and in the pathogenesis of many neurodegenerative disorders. Increased levels of Chitinases, in particular Chitotriosidase (CHIT-1) and chitinase-3-like protein 1 (CHI3L1), have been found increased in several neurodegenerative disorders. Although having important biological roles in inflammation, to date, the molecular mechanisms of Chitinase involvement in the pathogenesis of neurodegenerative disorders is not well-elucidated. Several studies showed that some Chitinases could be assumed as markers for diagnosis, prognosis, activity, and severity of a disease and therefore can be helpful in the choice of treatment. However, some studies showed controversial results. This review will discuss the potential of Chitinases in the pathogenesis of some neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, to understand their role as distinctive biomarkers of neuronal cell activity during neuroinflammatory processes. Knowledge of the role of Chitinases in neuronal cell activation could allow for the development of new methodologies for downregulating neuroinflammation and consequently for diminishing negative neurological disease outcomes.

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“…[6][7][8] The blood-brain barrier contains non-fenestrated brain capillaries that restrict the free diffusion of solutes and cells into the central nervous system (CNS), which normally protects the CNS from peripheral toxins, pathogens, and inflammation. Although many neurologic diseases include blood-brain barrier dysfunction, including multiple sclerosis, 9 cerebrovascular injury, 10 and Alzheimer's disease, 11 its role in postoperative delirium is unclear. 12 Blood-brain barrier function in humans can be measured by the cerebrospinal fluid-to-plasma albumin ratio (CPAR), since albumin is an abundant peripherally-synthesized plasma protein that does not diffuse through an intact blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults

Devinney

Wong

Wright

et al. 2023

Preprint

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Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, the role of postoperative blood-brain barrier dysfunction in postoperative delirium and overall recovery is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling was prospectively performed before and after non-cardiac, non-neurologic surgery in older adults. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). Results: Of 207 patients with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median postoperative change 0.28, [IQR] [-0.48- 1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (OR, 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (incidence rate ratio, 1.15 [95% CI 1.09-1.22]; p<0.001) Interpretation: These data demonstrate that postoperative increases in blood-brain barrier permeability are associated with increased delirium risk and increased postoperative hospital length of stay. Although these findings do not establish causality, they suggest studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium risk and hospital length of stay.

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How does neurovascular unit dysfunction contribute to multiple sclerosis?

Cited by 20 publications

References 287 publications

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway

Chitinase Signature in the Plasticity of Neurodegenerative Diseases

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults

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