Cerebral Cavernous Malformation Proteins in Barrier Maintenance and Regulation

Cerebral cavernous malformation (CCM) is a disease characterized by mulberry shaped clusters of dilated microvessels, primarily in the central nervous system. Such lesions can cause seizures, headaches, and stroke from brain bleeding. Loss-of-function germline and somatic mutations of a group of genes, called CCM genes, have been attributed to disease pathogenesis. In this review, we discuss the impact of CCM gene encoded proteins on cellular signaling, barrier function of endothelium and epithelium, and their contribution to CCM and potentially other diseases.

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Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.789834 ◽

2021 ◽

Vol 13 ◽

Author(s):

Banglian Hu ◽

Shengshun Duan ◽

Ziwei Wang ◽

Xin Li ◽

Yuhang Zhou ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Disorders ◽

Neurological Diseases ◽

Colony Stimulating Factor ◽

Loss Of Function ◽

Axonal Spheroids ◽

The Central Nervous System ◽

Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

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Macrophages Enforce the Blood Nerve Barrier

10.1101/493494 ◽

2019 ◽

Author(s):

Liza Malong ◽

Ilaria Napoli ◽

Ian J White ◽

Salome Stierli ◽

Alessandro Bossio ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Barrier Function ◽

Cellular Composition ◽

Complete Coverage ◽

Therapeutic Delivery ◽

The Central Nervous System ◽

Low Levels ◽

Cellular Components ◽

Distinct Role

The specialised blood barriers of the nervous system are important for protecting the neural environment but can hinder therapeutic accessibility1,2. Studies in the central nervous system (CNS) have shown the importance of the cellular components of the neuro-vascular unit for blood-brain barrier (BBB) function. Whilst the endothelial cells (ECs) confer barrier function with specialised tight junctions (TJs) and low levels of transcytosis, pericytes and astrocytes provide complete coverage of the ECs and both deliver essential signals for the development and maintenance of the BBB3–9. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system (PNS) remains poorly defined10. Here, we show that the vascular unit in the PNS has a distinct cellular composition with only partial coverage of the BNB-forming ECs. Using a mouse model, in which barrier function can be controlled11, we show the BNB, while less tight than the BBB, is maintained by low levels of transcytosis and the TJs of the ECs, with opening of the barrier associated with increased transcytosis. Importantly, we find that while ECs of the PNS have higher transcytosis rates than those of the CNS, the barrier is reinforced by resident macrophages that specifically engulf leaked material. This identifies a distinct role for macrophages as an important component of the BNB acting to protect the PNS environment with implications for improving therapeutic delivery to this tissue.

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The variable monoaminergic outcomes of cleaner fish brains when facing different social and mutualistic contexts

PeerJ ◽

10.7717/peerj.4830 ◽

2018 ◽

Vol 6 ◽

pp. e4830 ◽

Cited By ~ 6

Author(s):

Murilo S. de Abreu ◽

João P.M. Messias ◽

Per-Ove Thörnqvist ◽

Svante Winberg ◽

Marta C. Soares

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Social Behaviour ◽

Visual Assessment ◽

Physical Contact ◽

Specific Response ◽

Dopaminergic Activity ◽

Cleaner Fish ◽

The Central Nervous System ◽

The Impact

The monoamines serotonin and dopamine are important neuromodulators present in the central nervous system, known to be active regulators of social behaviour in fish as in other vertebrates. Our aim was to investigate the region-specific brain monoaminergic differences arising when individual cleaners face a client (mutualistic context) compared to when they are introduced to another conspecific (conspecific context), and to understand the relevance of visual assessment compared to the impact of physical contact with any partner. We demonstrated that serotoninergic activity at the diencephalon responds mostly to the absence of physical contact with clients whereas cerebellar dopaminergic activity responds to actual cleaning engagement. We provide first insights on the brain’s monoaminergic (region-specific) response variations, involved in the expression of cleaner fishes’ mutualistic and conspecific behaviour. These results contribute to a better understanding of the monoaminergic activity in accordance to different socio-behavioural contexts.

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Design, fabrication, and testing of a bioprinted nerve graft

10.32469/10355/71260 ◽

2016 ◽

Author(s):

◽

Christopher M. Owens

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nerve Graft ◽

Loss Of Function ◽

Vitro Assay ◽

Central Nervous System Damage ◽

In Vivo Animal Model ◽

The Central Nervous System

Injuries to nerves vary in their consequences, from weakened sensation and motor function to partial or complete paralysis. In the latter case, affecting about twenty thousand Americans yearly, the injury is debilitating and results in a significant decrease in quality of life. Currently there is no effective treatment for damage to the central nervous system, in particular the spinal cord. Compared to the injuries to the central nervous system, damage in the peripheral nerves, is more common, with about sixty thousand occurrences annually. The cost of associated surgical procedures and due to loss of function is in the billions. In this thesis we present work towards the construction and testing of a fully cellular, patented nerve graft, one amongst the first of its kind. For the fabrication of the graft we are the first to employ bioprinting (either implemented through a special purpose 3D bioprinter or manually), a novel tissue engineering method rapidly gaining acceptance and utility. We first review the status of bioprinting. We then detail the fabrication process. Next we report on the testing of the graft in an in vivo animal model through electrophysiology and histology. This is followed by the introduction of a novel in vitro model, aimed at providing a fast, inexpensive and reliable method to test engineered nerve grafts. We describe our work on the optimization of the in vitro assay and then the testing of the graft using the optimized assay. We conclude with a summary of our accomplishments and make suggestions for some exciting future applications of our approach.

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Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Frontiers in Neurology ◽

10.3389/fneur.2020.592888 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lintao Wang ◽

Zhiguang Ren ◽

Li Ma ◽

Yanjie Han ◽

Wenqiang Wei ◽

...

Keyword(s):

Public Health ◽

Central Nervous System ◽

Nervous System ◽

Neurological Diseases ◽

Public Health Problem ◽

Neurological Complications ◽

Major Public Health Problem ◽

The Central Nervous System ◽

The Impact ◽

Great Harm

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

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Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0186 ◽

2017 ◽

Vol 30 (10) ◽

Cited By ~ 3

Author(s):

Onur Akın ◽

İbrahim Eker ◽

Mutluay Arslan ◽

Süleyman Tolga Yavuz ◽

Sevil Akman ◽

...

Keyword(s):

Insulin Resistance ◽

Central Nervous System ◽

Nervous System ◽

Healthy Children ◽

Model Assessment ◽

Obese Children ◽

Neurocognitive Functions ◽

The Central Nervous System ◽

Biochemical Indices ◽

The Impact

AbstractBackground:Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children.Methods:Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups.Results:Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IR– groups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessment-insulin resistance (HOMA-IR) values. EEGs showed significantly more frequent ‘slowing during hyperventilation’ (SDHs) in obese children than non-obese children.Conclusions:Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR. An early examination of cognitive functions may help identify and correct such abnormalities in obese children.

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HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

Multiple Sclerosis Journal ◽

10.1177/1352458510376177 ◽

2010 ◽

Vol 16 (10) ◽

pp. 1173-1177 ◽

Cited By ~ 10

Author(s):

M. Shahbazi ◽

H. Ebadi ◽

D. Fathi ◽

D. Roshandel ◽

M. Mohamadhosseni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Promoter Polymorphism ◽

Exact Test ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Pcr Method ◽

Multiple Sclerosis Patients ◽

The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

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The impact of high and low dose ionising radiation on the central nervous system

Redox Biology ◽

10.1016/j.redox.2016.08.002 ◽

2016 ◽

Vol 9 ◽

pp. 144-156 ◽

Cited By ~ 38

Author(s):

Calina Betlazar ◽

Ryan J. Middleton ◽

Richard B. Banati ◽

Guo-Jun Liu

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Low Dose ◽

Ionising Radiation ◽

The Central Nervous System ◽

The Impact

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Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

Mediators of Inflammation ◽

10.1155/2017/9478542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 47

Author(s):

Ilse Bollaerts ◽

Jessie Van houcke ◽

Lien Andries ◽

Lies De Groef ◽

Lieve Moons

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Axonal Regeneration ◽

Current Knowledge ◽

Cord Injury ◽

The Central Nervous System ◽

Novel Therapeutic Strategies ◽

The Impact ◽

Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

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