Inflaming the Brain

Ahn, Hyung Jin; Baker, Sarah K.; Norris, Erin H.; Strickland, Sidney

doi:10.1016/j.neuron.2019.03.007

“…Fibrinogen is an important part of the coagulation cascade and can enter and deposit in the brain following vascular injury or compromise of the blood-brain-barrier. It has been recently shown to have a pleotropic role in the CNS including activation of inflammation, induction of scar formation, promotion of cognitive decline and inhibition of repair [20,21]. Mitochondrial import membrane translocases have an implied role in several neurological disease conditions [22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Tobieson

¹

,

Czifra

²

,

Wåhlén

³

et al. 2020

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Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

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“…Fibrinogen is an important part of the coagulation cascade and can enter and deposit in the brain following vascular injury or compromise of the blood-brain-barrier. It has been recently shown to have a pleotropic role in the CNS including activation of in ammation, induction of scar formation, promotion of cognitive decline and inhibition of repair (20,21). Mitochondrial import membrane translocases have an implied role in several neurological disease conditions (22)(23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Tobieson

¹

,

Czifra

²

,

Wåhlén

³

et al. 2020

Preprint

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Background: Cerebral microdialysis (CMD) is a minimally invasive technique for sampling the interstitial fluid in human brain tissue. CMD allows monitoring the metabolic state of tissue, as well as sampling macromolecules such as proteins and peptides. Recovery of proteins or peptides can be hampered by their adsorption to the CMD membrane as has been previously shown in-vitro, however, protein adsorption to CMD membranes has not been characterized following implantation in human brain tissue. Methods: In this paper, we describe the pattern of proteins adsorbed to CMD membranes compared to that of the microdialysate and of cerebrospinal fluid (CSF). We retrieved CMD membranes from three surgically treated intracerebral hemorrhage (ICH) patients, and analyzed protein adsorption to the membranes using two-dimensional gel electrophoresis (2-DE) in combination with nano-liquid mass spectrometry. We compared the proteome profile of three compartments; the CMD membrane, the microdialysate and ventricular CSF collected at time of CMD removal. Results: We found unique protein patterns in the molecular weight range of 10-35 kDa for each of the three compartments. Conclusion: This study highlights the importance of analyzing the membranes in addition to the microdialysate when using CMD to sample proteins for biomarker investigation.

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“…[29][30][31] Additionally, blood-derived fibrin acts on CD11b/CD18 of microglia, causing damage to synapses and also causing cognitive impairment. 32 Belfiore, R. et al evaluated female 3xTg-AD and nontransgenic (NonTg) mouse models and found that the Aβ load and Tau protein caused by Aβ deposition are located at Thr212/Ser214 or Ser202/Thr205 and Ser422. The phosphorylation of Tau protein leads to a neuroinflammatory response, which can also lead to a gradual decline in cognitive function.…”

Section: The Influence Mechanism Of Microglia On Cognitive Functionmentioning

confidence: 99%

“…The lack or downregulation of the receptors SIRPα and CB1 on microglia and the receptor CD2000 on neurons will lead to microglia, and phagocytosis‐mediated increases in synapse loss and cognitive impairment 29–31 . Additionally, blood‐derived fibrin acts on CD11b/CD18 of microglia, causing damage to synapses and also causing cognitive impairment 32 …”

Section: Ad and Microgliamentioning

confidence: 99%

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The role of microglia in Alzheimer's disease and progress of treatment

Guan

¹

,

Zhang

²

,

Wang

³

et al. 2022

Ibrain

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Microglia are permanent immune cells of the central nervous system.Microglia play an important role in the pathological process of Alzheimer's disease (AD). They are mainly involved in the uptake and clearance of amyloid-β (Aβ), as well as the formation of neuroinflammation. We found that overactivated microglia increase Aβ and Tau, and Aβ and Tau in turn act as activators of microglia. Additionally, various cytokines and proteins, high cholesterol, and telomere shortening are all associated with microglia activation. More activated microglia induce the release of inflammatory and antiinflammatory factors to regulate inflammation, while microglia express multiple homologous receptors that bind to neuroimmunomodulators to prevent microglia overactivation. Moreover, aging of the body promotes neuroinflammation by increasing the response to IFN-γ (interferon-γ), and aging of the microglia themselves promotes AD by inducing the accumulation of large amounts of iron and reducing autophagy by regulating protein levels. Cognitive dysfunction occurs when activated microglia induce an increase in beta oligomers, promoting the production of pro-inflammatory factors that alter the shape, composition, and density of synapses. Based on their correlation, microglia-mediated AD therapy as well as the corresponding targets and drugs are discussed. In contrast to similar reviews, this article also summarizes some novel microglia-mediated AD treatment methods over the recent years. K E Y W O R D S aging, Alzheimer disease, growth and development, microglia 1 | INTRODUCTION 1.1 | Alzheimer diseaseAlzheimer's disease (AD), also known as senile dementia, is a typical neurodegenerative disease, mainly manifested as progressive memory impairment, cognitive dysfunction, language impairment, and personality changes and other neuropsychiatric symptoms, and adversely affects patients' social, professional, and daily lives. With the aging of the population, about one-third of the elderly over the age of 85 years will suffer from AD,

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Inflaming the Brain

Abstract: Proteomic analysis of Zika virus infected primary human fetal neural progenitors suggests a role for doublecortin in the pathological consequences of infection in the cortex. Front. Microbiol. 9, 1067.

Cited by 7 publications

References 10 publications

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

Proteomic investigation of protein adsorption to cerebral microdialysis membranes in surgically treated intracerebral hemorrhage patients - a pilot study

The role of microglia in Alzheimer's disease and progress of treatment

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