The role of inflammasomes in vascular cognitive impairment

Poh, Luting; Sim, Wei Liang; Jo, Dong-Gyu; Dinh, Quynh Nhu; Drummond, Grant R; Sobey, Christopher G.; Chen, Christopher; Lai, Mitchell K.P.; Fann, David Y.; Arumugam, Thiruma V.

doi:10.1186/s13024-021-00506-8

Cited by 54 publications

(32 citation statements)

References 333 publications

(465 reference statements)

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“…It is caused by vascular alterations that induce dysfunction and damage to the cerebral vasculature, leading to cerebral blood flow (CBF) disruption, brain injury, and eventually cognitive impairment and memory loss [ 1 ]. Endothelial dysfunction, glial activation, demyelination, and blood–brain barrier collapse are among the neurovascular dysfunctions seen in VaD patients [ 2 ]. Diabetes, high blood pressure, smoking, and high cholesterol are all risk factors for VaD [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

et al. 2022

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Vascular dementia (VaD) is the second leading cause of dementia. The majority of VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products are receiving increasing attention for the treatment of neuroinflammatory diseases. The aim of this study was to investigate the molecular pathways underlying the protective effects of fisetin, a flavonoid present in many fruits and vegetables, in a mouse model of VaD induced by repeated ischemia-reperfusion (IR) of the total bilateral carotid artery. Here, we found that VaD caused brain injury, lipid peroxidation, and neuronal death in the hippocampus, as well as astrocyte and microglial activation, and reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, VaD induced the activation of inflammasome components (NLRP-3, ASC, and caspase 1), and their downstream products (IL-1β and IL-18) release and promote activation of apoptotic cell death. Fisetin attenuated histological injury, malondialdehyde levels, inflammasome pathway activation, apoptosis, as well as increased BDNF expression, reduced astrocyte, microglial activation, and cognitive deficits. In conclusion, the protective effects of fisetin could be due to the inhibition of the ROS-induced activation of NF-κB/NLRP3 inflammasome together with the activation of antioxidant Nrf2/HO-1, suggesting a possible crosstalk between these molecular pathways.

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Section: Introductionmentioning

confidence: 99%

Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

et al. 2022

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“…The biological cognitive process is an intelligent process in which the body recognizes and acquires knowledge, including learning, memory, language, thinking, spirit, emotion, and other behaviors. Cognitive impairment refers to abnormalities in the modules related to learning and memory as well as thinking and judgment of the brain in the process of advanced intelligent processing, resulting in learning and memory dysfunction [ 19 , 20 ]. Any factors that cause abnormalities in the brain function and structure may lead to cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Yisui Multipurpose Soup’s Amelioration on D-Galactose-Induced Neuronal Cells

Yan

Zhang

Xiao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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This study clarified the regulatory effect of Yisui multipurpose Soup towards D-galactose-induced cognitive impairment cell model on the molecular level. We first constructed and cultured the cell model of cognitive impairment induced by D-galactose in neurons in vitro and then cultured the cells in the medium supplemented with different doses of drug-containing serum of Yisui multipurpose soup. Expressions of inflammatory cytokine tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), nitric oxide (NO), and interleukin-1β (IL-1β) were assessed by the ELISA and western blot, and cell apoptosis was determined by flow cytometry and TUNEL. The expression changes of apoptosis-related proteins Bcl-2 and Bax were estimated by immunofluorescence, qPCR, and western blot. Finally, we analyzed and made the network interaction diagram of Yisui multipurpose soup-components-targets through the network pharmacology method, from which we could learn that there were 1104 gene targets related to vascular cognitive impairment (VCI) and 1071 component targets of Yisui multipurpose soup. And there were 251 overlapping genes, mainly gathering in protein binding, protein modification, MAPK signaling pathway, and calcium signaling pathway. The expressions of TNF-α, iNOS, NO, and IL-1β were significantly decreased after the culture medium was replaced by medium containing drug serum. We also found that the effect of high-dose drug-containing serum on the expression of inflammatory factors was better than that of low dose. The Yisui multipurpose soup drug serum in the medium not only significantly increased Bcl-2 expression and effectively reduced Bax expression, but also inhibited the apoptosis of neurons induced by D-galactose. In conclusion, Yisui multipurpose soup could effectively protect D-galactose-induced neuronal cell cognitive impairment by orchestrating expressions of the inflammatory factors TNF-α, iNOS, NO, and IL-1β and the apoptosis-related proteins Bcl-2 and Bax.

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“…NRLP3 is a component of the innate immune system and activated in AD brains, forming the NLP3 inflammosome complex in association with other proteins, promoting the release of proinflammatory IL-1β and IL-18. Interestingly, recent evidence suggests the NRLP3 inflammosome is also activated in VaD as a result of chronic cerebral hypoperfusion ( 75 ). Mouse models of AD deficient for NLRP3 inflammosome are protected from amyloid pathology ( 76 ) and the inflammosome in microglia plays a role in AD progression and in the spread of amyloid pathology ( 77 ).…”

Section: Alzheimer’s Disease and Neuroinflammationmentioning

confidence: 99%

Non-Communicable Neurological Disorders and Neuroinflammation

et al. 2022

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Traumatic brain injury, stroke, and neurodegenerative diseases represent a major cause of morbidity and mortality in Africa, as in the rest of the world. Traumatic brain and spinal cord injuries specifically represent a leading cause of disability in the younger population. Stroke and neurodegenerative disorders predominantly target the elderly and are a major concern in Africa, since their rate of increase among the ageing is the fastest in the world. Neuroimmunology is usually not associated with non-communicable neurological disorders, as the role of neuroinflammation is not often considered when evaluating their cause and pathogenesis. However, substantial evidence indicates that neuroinflammation is extremely relevant in determining the consequences of non-communicable neurological disorders, both for its protective abilities as well as for its destructive capacity. We review here current knowledge on the contribution of neuroinflammation and neuroimmunology to the pathogenesis of traumatic injuries, stroke and neurodegenerative diseases, with a particular focus on problems that are already a major issue in Africa, like traumatic brain injury, and on emerging disorders such as dementias.

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The role of inflammasomes in vascular cognitive impairment

Cited by 54 publications

References 333 publications

Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

Effect of Yisui Multipurpose Soup’s Amelioration on D-Galactose-Induced Neuronal Cells

Non-Communicable Neurological Disorders and Neuroinflammation

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