White Matter and Neuroprotection in Alzheimer’s Dementia

Lorenzini, Luca; Fernández, Mercedes; Baldassarro, Vito Antonio; Bighinati, Andrea; Giuliani, Alessandro; Calzà, Laura; Giardino, Luciana

doi:10.3390/molecules25030503

Cited by 19 publications

(9 citation statements)

References 89 publications

(104 reference statements)

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“…However, it is generally accepted that the NVU is a structural unit that includes both the glio-vascular module and neurons. In addition, immune and inflammatory cells, such as microglia [ 32 , 33 , 34 , 35 ] and oligodendrocytes in the white matter [ 36 , 37 , 38 ], targets of research on cerebral white matter disorders, are also now considered to be important components of the NVU [ 19 , 20 , 21 ] ( Figure 1 ).…”

Section: Construction Of the Virtual Concept Of An Nvumentioning

confidence: 99%

“…The goal has now shifted from “neuroprotection” to “whole NVU protection” (in other words, cerebral “cytoprotection” or “cerebroprotection”) [ 41 , 42 ]. In this context, the importance of astrocytes in the NVU is gaining more attention at present, because these cells play a neuroprotective role in conjunction with the microglia [ 32 , 33 , 34 , 35 ] and oligodendrocytes [ 36 , 37 , 38 ]. In particular, the influence of “help-me signals” emitted from vulnerable neurons in the early stages of ischemia on the astrocytes has attracted a lot of attention in recent years [ 41 , 42 ].…”

Section: Current Status Of Research On the Nvu And The Positioning Of...mentioning

confidence: 99%

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Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Takahashi

2022

Cells

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The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between the neural cells and blood vessels in the human brain, focused mainly on the brain gray matter. The major components of the NVU are the neurons, astrocytes (astroglia), microvessels, pericytes, and microglia. In addition, we believe that oligodendrocytes should also be included as an indispensable component of the NVU in the white matter. Of all these components, astrocytes in particular have attracted the interest of researchers because of their unique anatomical location; these cells are interposed between the neurons and the microvessels of the brain. Their location suggests that astrocytes might regulate the cerebral blood flow (CBF) in response to neuronal activity, so as to ensure an adequate supply of glucose and oxygen to meet the metabolic demands of the neurons. In fact, the adult human brain, which accounts for only 2% of the entire body weight, consumes approximately 20–25% of the total amount of glucose and oxygen consumed by the whole body. The brain needs a continuous supply of these essential energy sources through the CBF, because there are practically no stores of glucose or oxygen in the brain; both acute and chronic cessation of CBF can adversely affect brain functions. In addition, another important putative function of the NVU is the elimination of heat and waste materials produced by neuronal activity. Recent evidence suggests that astrocytes play pivotal roles not only in supplying glucose, but also fatty acids and amino acids to neurons. Loss of astrocytic support can be expected to lead to malfunction of the NVU as a whole, which underlies numerous neurological disorders. In this review, we shall focus on historical and recent findings with regard to the metabolic contributions of astrocytes in the NVU.

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Section: Construction Of the Virtual Concept Of An Nvumentioning

confidence: 99%

Section: Current Status Of Research On the Nvu And The Positioning Of...mentioning

confidence: 99%

Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Takahashi

2022

Cells

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“…Myelin loss is a common feature in numerous neurodegenerative diseases, which was explained as a combinative result of demyelination and axon degeneration (Casella et al, 2020;De Strooper & Karran, 2016;Lorenzini et al, 2020). Demyelination impairs neuronal function by disrupting action potential propagation.…”

Section: Demyelination and Neuronal Dysfunctionsmentioning

confidence: 99%

Oligodendrocytes and myelin: Active players in neurodegenerative brains?

Chen

Wang

Huang

et al. 2022

Developmental Neurobiology

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Oligodendrocytes (OLs) are a major type of glial cells in the central nervous system that generate multiple myelin sheaths to wrap axons. Myelin ensures fast and efficient propagation of action potentials along axons and supports neurons with nourishment. The decay of OLs and myelin has been implicated in age-related neurodegenerative diseases and these changes are generally considered as an inevitable result of neuron loss and axon degeneration. Noticeably, OLs and myelin undergo dynamic changes in healthy adult brains, that is, newly formed OLs are continuously added throughout life from the differentiation of oligodendrocyte precursor cells (OPCs) and the pre-existing myelin sheaths may undergo degeneration or remodeling. Increasing evidence has shown that changes in OLs and myelin are present in the early stages of neurodegenerative diseases, and even prior to significant neuronal loss and functional deficits. More importantly, oligodendroglia-specific manipulation, by either deletion of the disease gene or enhancement of myelin renewal, can alleviate functional impairments in neurodegenerative animal models. These findings underscore the possibility that OLs and myelin are not passively but actively involved in neurodegenerative diseases and may play an important role in modulating neuronal function and survival. In this review, we summarize recent work characterizing by OLs and myelin changes in both healthy and neurodegenerative brains and discuss the potential of targeting oligodendroglial cells in treating neurodegenerative diseases.

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“…Besides, in ammatory mediators produced by damaged cells recruit cerebral microglia and peripheral immune cells which release in ammatory factors, thus promoting secondary neuronal damage [7]. White matter, which constructs 50% human brain, is mainly consisted of neurite and myelin sheaths, and it has been proved necessary for advanced brain functions [8]. Compared to grey matter (GM), WM is more susceptible to TBI [9].…”

Section: Introductionmentioning

confidence: 99%

Cordycepin Confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

Wei

Huang

Luo

et al. 2021

Preprint

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Background Traumatic brain injury (TBI) secondary injury, especially white matter injury (WMI), is highly sensitive to neuroinflammation, which further leads to unfavored long-term outcomes. Although the cross-talk between the three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, play a role in the vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract from cordyceps militaris, can inhibit TBI-induced neuroinflammation although the long-term effects of cordycepin remain unknown. Here, we report our investigation of cordycepin’s long-term neuroprotective function and its underlying immunological mechanism. Methods TBI mice model was established with a controlled cortical impact (CCI) method. Cordycepin was intraperitoneally administered twice daily for a week. Neurological outcomes were assessed by behavioral tests, including grid walking test, cylinder test, wire hang test, and rotarod test. Immunofluorescence staining, transmission electron microscopy, and electrophysiology recording were employed to assess histological and functional lesions. Quantitative-PCR and flow cytometry were used to detect neuroinflammation. The tracers of Sulfo-NHS-biotin and Evans blue were assessed for the Blood-brain barrier (BBB) leakage. Western blot and gelatin zymography were used to analyze protein activity or expression. Neutrophil depletion in vivo was performed via using Ly6G antibody intraperitoneal injection. Results Cordycepin administration ameliorated long-term neurological deficits and reduced neuronal tissue loss in TBI mice. Meanwhile, the long-term integrity of white matter was also preserved, which was revealed in multiple dimensions, such as morphology, histology, ultrastructure, and electrical conductivity. Cordycepin administration inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization after TBI. BBB breach was attenuated by cordycepin administration at 3d after TBI. Cordycepin suppressed the activities of MMP-2 and MMP-9 and the neutrophil infiltration at 3d after TBI. Moreover, neutrophil depletion provided a cordycepin-like effect, and cordycepin administration united with neutrophil depletion didn’t show a benefit of superposition. Conclusions The long-term neuroprotective function of cordycepin was via suppressing neutrophil infiltration, thereby preserving BBB integrity and changing microglia/macrophage polarization. These findings provide significant clinical potentials to improve the quality of life for TBI patients.

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White Matter and Neuroprotection in Alzheimer’s Dementia

Cited by 19 publications

References 89 publications

Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Metabolic Contribution and Cerebral Blood Flow Regulation by Astrocytes in the Neurovascular Unit

Oligodendrocytes and myelin: Active players in neurodegenerative brains?

Cordycepin Confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury

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