Blood–brain barrier dysfunction in immuno-mediated neurological diseases

Shimizu, Fumitaka; Nishihara, Hideaki; Kanda, Takashi

doi:10.1080/25785826.2018.1531190

Cited by 61 publications

(58 citation statements)

References 88 publications

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“…BBB disruption is a hallmark of NMOSD that has been demonstrated in magnetic resonance imaging (MRI) with gadolinium contrast-enhanced lesions, particularly in the acute stage of NMOSD. 6,8,9 BBB destruction is essential for AQP4-IgGs to enter the CNS. [9][10][11] BBB breakdown regulates the expression of endothelial cell adhesion molecules that tightly mediate immune cell extravasation and trafficking into the CNS as well as contribute to modulation of vascular integrity.…”

Section: Introductionmentioning

confidence: 99%

“…14 Studies have suggested that VCAM1, ICAM1, and PECAM1 are instrumental in BBB disruption for transmigration of activated peripheral lymphocytic cells to the CNS. 6,12,13,15 In MRI, NMOSD is characterized by longitudinally extensive gadolinium contrast-enhanced lesions at the spinal cord and/or optic nerves, whereas periventricular plaques with partial ring enhancement are frequently observed in MS. 16 The differences in patterns and distributions of contrast-enhanced lesions suggest these two diseases generate different BBB breakdown patterns. The discovery of BBB-reactive antibodies, such as GRP78 antibodies in NMOSD and galactin-3 antibodies in MS, further implies that the BBB breakdown mechanisms differ between these two neuroinflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

“…The discovery of BBB-reactive antibodies, such as GRP78 antibodies in NMOSD and galactin-3 antibodies in MS, further implies that the BBB breakdown mechanisms differ between these two neuroinflammatory diseases. 6,16 Although the exact role of BBB breakdown in the pathogenesis of NMOSD remains elusive, cell adhesion molecules may represent BBB function and serve as disease activity biomarkers for many neuroinflammatory diseases of the CNS. 5,9,17 Therefore, we evaluated the profile of five cell adhesion molecules, ICAM1, ICAM2, VCAM1, PECAM1, and NCAM1, in patients with NMOSD.…”

Section: Introductionmentioning

confidence: 99%

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Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Chang

Chen

et al. 2020

Ann Clin Transl Neurol

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Chang

Chen

et al. 2020

Ann Clin Transl Neurol

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“…In summary, we conclude that biexponential ASL modeling is a promising approach to non-invasively 34 investigate the status of the BBB in humans, which remains of ongoing interest in the research of numerous pathologies like Alzheimer's disease, multiple sclerosis and brain tumors. 38,42,43…”

Section: Discussionmentioning

confidence: 99%

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings

et al. 2020

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Blood–brain barrier (BBB) permeability assessment remains of ongoing interest in clinical practice and research. Transitions between intravascular (IV) and extravascular (EV) gray matter (GM) compartments may provide information regarding the microstructural status of the BBB. Due to different transverse relaxation times (T2) of water protons in vessels and GM, it is possible to determine the compartment in which these protons are located. This work presents and investigates the feasibility of a simplified analytical approach for compartmentalizing the proportions of magnetically marked water protons into IV and EV GM components by biexponentially modeling T2‐weighted arterial spin labeling (ASL) data. Numerous model assumptions were used to stabilize the fit and achieve in vivo applicability. Particularly, transverse relaxation times of IV and EV water protons were determined from the analysis of two supporting T2‐weighted ASL measurements, utilizing a monoexponential signal model. This stabilized a two‐parameter biexponential fit of ASL data with T2 preparation (PLD = 0.9/1.2/1.5/1.8 s, TET2Prep = 0/30/40/60/80/120/160 ms), which thereby robustly provided estimates of the IV and EV compartment fractions. Experiments were conducted with three healthy volunteers in a 3 T scanner. Averaged over all subjects, the labeled water protons inherit T2,IV = 200 ± 18 ms initially and adapt T2,EV = 91 ± 2 ms with a longer retention time in cerebral structures. Accordingly, the EVlocated ASL signal fraction rises with increasing PLD from 0.31 ± 0.11 at the shortest PLD of 0.9 s to 0.73 ± 0.02 at the longest PLD of 1.8s. These results indicate a transition of the water protons from IV to EV space. The findings support the potential of biexponential modeling for compartmentalizing ASL spin fractions between IV and EV space. The novel integration of monoexponential parameter estimates stabilizes the two‐compartment model fit, suggesting that this technique is suitable for robustly estimating the BBB permeability in vivo.

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“…Astrocytes are the most abundant cell type in the central nervous system and play a fundamental role in several cerebral functions such as maintenance of the blood-brain barrier, maintenance of ionic homeostasis, metabolic support to neurons and uptake of neurotransmitters of glutamate and GABA by specific transporters [1][2][3]. They are also involved in synaptogenesis and development of neuronal circuits by facilitating release of gliotransmitters [4].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Stat3 Phosphorylation Attenuates Impairments in Learning and Memory in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

Choi

Kim

Yang

et al. 2020

Preprint

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The novel functions of astrocytes under normal conditions have been extensively investigated in terms of synaptogenesis and memory formation. Meanwhile, the pathophysiological roles of astrocytes in the reactive state are thought to have important significance in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the detailed mechanisms underlying the transition of astrocytes from the resting state to the reactive state during neurodegenerative disease largely remain to be defined. Here, we investigated the pathways involved in activating astrocytes from the resting state to the reactive state in primary cultured astrocytes treated with oligomeric Aβ and in the hippocampus of 5XFAD mice, an animal model of AD. Treatment with oligomeric Aβ induced an increase in reactive astrocytes, as assessed by the protein level of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes and this increase was caused by STAT3 phosphorylation in primary cultured astrocytes. The administration of Stattic, an inhibitor of STAT3, rescued the activation of astrocytes in primary cultured astrocytes and in the hippocampus of 6-month-old 5XFAD mice as well as impairments in learning and memory. Collectively, these results demonstrated that reactive astrocytes in the AD brain are induced via STAT3 phosphorylation and that the increase in reactive astrocytes and the impairments in learning and memory observed in 5XFAD mice are rescued by STAT3 inhibition, suggesting that the inhibition of STAT3 phosphorylation in astrocytes may be a novel therapeutic target for cognitive impairment in AD.

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Blood–brain barrier dysfunction in immuno-mediated neurological diseases

Cited by 61 publications

References 88 publications

Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings

Inhibition of Stat3 Phosphorylation Attenuates Impairments in Learning and Memory in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

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Blood–brain barrier dysfunction in immuno-mediated neurological diseases

Cited by 61 publications

References 88 publications

Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T2‐weightings

Inhibition of Stat3 Phosphorylation Attenuates Impairments in Learning and Memory in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

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Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings