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Which Neuroglial Cell Helps Form The Blood Brain Barrier

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Organization Of A Neurovascular Unit

Glial cells forming blood brain barrier are formed of | 12 | STRUCTURAL ORGANISATION IN ANIMALS…

A neurovascular unit is organized by complex associations between endothelial cells, extra-cellular matrix, basal lamina, pericytes, closely juxtaposed neurons, and astrocytes . The components of the neurovascular unit maintain dynamic interactions with each other and play an important role in cerebrovascular function . Contact and communications between cells of the neurovascular unit regulate CNS development and synaptic activity and influence permeability properties of the BBB . A major function of the neurovascular unit is to regulate the transport and diffusion properties of brain capillary endothelial cells that compose the BBB .

Within the neurovascular organization, further modular structures, termed the gliovascular units, are detected where individual astrocytic glia support the function of particular neuronal populations and communicate with associated segments of the microvasculature . Several recent studies have highlighted the importance of this modular organization in disease pathology and the cell-cell interactions that result in modulating the BBB.

Regulation Of The Bbb By Astrocytes

The persistence of a functional BBB throughout adulthood is maintained and regulated by numerous factors unique to the microniche of the neurovascular unit . AstrocyteBBBEC interactions are known to regulate EC morphology, angiogenesis, and to influence the phenotype of the barrier under physiological and pathological conditions .

Astrocytes are known to produce factors that modulate endothelial functioning during development and adulthood. One of these pathways is the Hedgehog signaling cascade known to be involved in embryonic morphogenesis, neuronal guidance, and angiogenesis. Astrocytes secrete Sonic Hh , and BBB ECs express the Hh receptor Patched-1, the signal transducer Smoothened , as well as transcription factors of the Gli family. Interestingly, transendothelial electrical resistance and permeability experiments showed that activation of the Hh pathway induced expression of junctional proteins and promoted a BBB phenotype. In addition, mice genetically engineered to lose the signal transducer Smo on ECs had a significant increase in BBB permeability that correlated with a decrease in junctional protein expression and disturbed BMs , supporting the concept that the Hh pathway has a significant influence on BBB function.

Microglia Ablation Under Pathological Conditions

Microglia are known to shift their phenotype from resting to an activated state upon any loss of brain homeostasis due to injury, infection, or neurodegenerative disease. This microglia activation is comprised of proliferation, migration toward a chemoattractant, reduction of cellular complexity as well as phagocytosis to clear the damaged tissue . The cellular response of microglia upon injury has been extensively described, however, both its functional impact on brain pathogenesis and its mechanism remain somewhat unclear. Because many contradictory findings have been reported with regard to microglia function after brain injury, microglia ablation studies continue to be performed .

To explain these variable observations between ablation studies, the same aspects that complicate the readout of the approaches carried out under healthy conditions certainly apply also here, and different disease models add another dimension of complexity. Although all these studies worked with CD11b-HSVTK transgenic mice, the ablation efficiency was highly variable, ranging from 50 to up to 90%, making a direct comparison between the models difficult. Besides the cloned mouse lines carrying different transgenes, the diverse injury paradigms that were performed in various CNS regions might play an additional role. The injury paradigms were performed at different ages of the experimental mice and it could be possible that microglia function changes during the process of aging.

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Uptake Of Amino Acids Into The Nervous System

Amino acids are not only required for protein synthesis, but particular amino acids or their direct derivatives are also used as neurotransmitters. Cells are able to generate most amino acids from intermediates of the citric acid cycle. However, some amino acids cannot be produced and thus their uptake and transport is essential. In Drosophila, 10 proteinogenic L-amino acids are essential: tryptophan, phenylalanine, leucine, histidine, valine, isoleucine, lysine, methionine, arginine, and threonine . Therefore, specific transport systems for these amino acids must be expressed by the SPG cells.

In vertebrates, nine distinct amino acid transport systems have been reported to be present at the brain capillary endothelium : the X-system is a high affinity, sodium-independent transport system for anionic amino acids, the L-system transports large neutral amino acids, the A-and ASC-systems transport small neutral amino acids, the Y+-system is a sodium-independent cationic amino acid transport system, the Bo+-system represents a high affinity transport system and transports both neutral and basic amino acids and the ß-system is a low capacity, sodium-dependent transporter for taurine and ß-alanine. The N-system mediates the sodium-dependent transport of L-glutamine, L-histidine and L-asparagine and the T-system transports thyroid hormones.

Table 4. Drosophila amino acid transporters.

Therapies To Increase Bbb Insulin Transport And Cns Insulin Levels

13 Nervous Tissue

In this review, we have summarized the detrimental effects of altered insulin signaling within specific cell types at the BBB. However, many of these detrimental effects are due to decreased exposure to insulin and hence insulin BBB transport. Therefore, if CNS insulin can be increased, some of these detrimental effects could be overcome. Alternative routes to increase CNS insulin has recently been reviewed by our group in detail . We have highlighted here a couple of therapies that are the most translational to increase CNS insulin levels.

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Regulation Of The Bbb Formation And Homeostasis

Although key properties of the BBB are manifested within the ECs, important transplantation studies have shown that they are regulated by interactions with the microenvironment of the CNS . The BBB is not one physiology, but a series of physiological properties that either need to be induced or inhibited in CNS ECs. Recent work has dissected the cellular and molecular mechanisms that regulate this process, and have identified that it is a complex process of induction and maintenance signaling interactions among CNS ECs and PCs, astrocytes, and immune cells.

What Are Glial Cells And What Do They Do

You’ve likely heard of the gray matter of the brain, which is made up of cells called neurons, but a lesser-known type of brain cell is what makes up the white matter. These are called glial cells.

Originally, glial cellsalso called glia or neurogliawere believed to just provide structural support. The word glia literally means “neural glue.”

Relatively recent discoveries have revealed that they perform all kinds of functions in the brain and the nerves that run throughout your body. As a result, research has exploded and we’ve learned volumes about them. Still, much more is left to learn.

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Microglia Ablation Under Healthy Conditions

Although several studies have depleted myeloid cells including microglia during development by inserting deleterious mutations in macrophage-specific genes , this review will focus only on microglia ablation studies performed in the adult brain.

TABLE 1.Microglial ablation approaches under healthy and pathological conditions.

Another commonly identified microglia property is their repopulation capacity: around 1 week after depletion, the whole population is restored without obvious deficits in microglia or in other glial cell populations. With this experimental system, one group identified a local progenitor cell population in the brain parenchyma expressing the stem cell marker nestin that accounted for the rapid repopulation of microglia. The cellular characteristics of these progenitors were, however, not described further .

In summary, the ablation studies of microglia in the adult healthy brain have revealed that these cells can, at least transiently, easily and efficiently be eliminated from the adult brain , though surviving progenitors rapidly repopulate the depleted areas. Moreover, microglia homeostasis seems to play an important role in the ongoing synapse formation in the brain these specific functions as well as mechanisms are however far from understood.

Carbohydrate Transporters In The Drosophila Blood

Glial Cells – Neuroanatomy Basics – Anatomy Tutorial

In total, 78 genes of Drosophila harbor a sugar transporter motif . Most of the encoded proteins, however, probably will not transport sugar across the plasma membrane but, as the SLC35 member Meigo, organize intracellular trafficking of different sugars to ensure glycosylation . As an alternative to trehalose, other sugars such as glucose or fructose could be taken up by the nervous system to meet the high neuronal energy demand. In vertebrates, the SLC2 family includes Glut2 and Glut5 transporters, which have been characterized as glucose and fructose transporters . No clear homolog of Glut2 and Glut5 can be identified in Drosophila, so it remains uncertain whether fructose can be imported into the nervous system. Interestingly, however, a fructose receptor has been shown to be expressed on several CNS neurons . Thus, a possible explanation for the apparent lack of Glut2 or Glut5 homologs is that fructose might be either generated in the brain or that the fructose sensing CNS neurons form dendrites that leave the CNS to detect fructose in the hemolymph.

Table 6. Drosophila sugar transporters.

In addition, members of the SLC5A family have been shown to mediate sodium-dependent glucose uptake . One Drosophila SLC5A family member is CG9657, which is also expressed in glial cells .

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Regulate Levels Of Neurotransmitters

The central and peripheral nervous systems share many of the same neurotransmitters, so the BBB helps to keep the central and peripheral transmitter pools separate, minimizing crosstalk and protecting the brain from unexpected changes in their plasma levels. For example, blood plasma contains high levels of the neuroexcitatory amino acid glutamate, which fluctuate significantly after the ingestion of food. High levels of glutamate in the brain ISF will have harmful effects on neuronal tissues. An example is a case of glutamate secretion from hypoxic neurons during ischemic stroke, which results in considerable and permanent neurotoxic/neuroexcitatory damage to neural tissue .

The transfer of neurotransmitters from the brain to blood primarily dependent on Na+-coupled and Na+-independent amino acid transporters. The BBB limits the influx of some amino acids including the neurotransmitters glutamate and glycine, while it effluxes many other essential amino acids. Hladky and Barrand reviewed comprehensively the transport of amino acids across the BBB with different transport systems based on the type of amino acids .

Bbb Disruption In Different Pathological Conditions

BBB dysfunction is reported in many CNS pathological conditions including multiple sclerosis hypoxic and ischemic insult Parkinsons and Alzheimers disease epilepsy brain tumors glaucoma , and lysosomal storage diseases . The observed barrier dysfunction can range from mild and transient changes in BBB permeability, resulting from tight junction opening, to chronic barrier breakdown, and changes in transport systems and enzymes can also occur. This process can also be associated with the degradation of the basement membrane . Microglial activation and infiltration of different plasma components and immune cells into the brain parenchyma result in disturbance of CNS homeostasis and variable damage to the surrounding brain. In most cases, it is not possible to determine whether barrier compromise is causal in disease onset or a result of neurological disease progression. Still, barrier disturbance can often be seen to contribute to and exacerbate developing pathology .

Table 1 Different CNS pathological conditions involving BBB disruption

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Astrocyte Ablation Under Pathological Conditions

Upon injury, astrocytes undergo a series of morphological and functional changes that are commonly summarized by the term astrogliosis. Astrogliosis displays a very broad spectrum of reactivity, the hallmarks thereof being the upregulation of structural proteins like GFAP or vimentin and the hypertrophy of both the cell body and the processes . Additionally, some quiescent astrocytes re-enter the cell cycle , although this occurs much later and to a lesser extent than in microglia or NG2-glia. Reactive astrocytes are also known to elongate around the lesion core and to release a cascade of inflammatory signals that can strongly affect the pathological outcome . Interestingly, as shown by repetitive in vivo imaging, astrocytes are unlike microglia and NG2-glia unable to migrate into the injury core after mechanical injury . Although many aspects of astrocyte-specific reactions to injury are already known, their precise role in scar formation under different pathological conditions remains unresolved. As this question has long been of great interest, studies that specifically ablate these scar forming astrocytes have already been reported almost 20 years ago.

The Bbb Can Be Broken Down By:

ScienceNectar : July 2012
  • Hypertension : highblood pressure opens the BBB.
  • Development: the BBB is present, but may be not fully formed at birth.
  • Hyperosmolitity: a high concentration of asubstance in the blood can open the BBB.
  • Microwaves: exposure to microwaves can openthe BBB.
  • Radiation: exposure to radiation can open theBBB.
  • Infection: exposure to infectious agents canopen the BBB.
  • Trauma, Ischemia, Inflammation, Pressure:injury to the brain can open the BBB.
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    The Nervous System Of Drosophila

    Drosophila is a holometabolic insect. Following 1 day of embryogenesis, three larval stages spread over the next 4 days. During the subsequent pupal stage, which covers another 5 days, metamorphosis takes place and the imago, the adult fly, emerges. Accordingly, the nervous system of Drosophila develops in two phases.

    The larval nervous system originates from stem cells called neuroblasts that delaminate in five waves shortly after gastrulation into the interior of the embryo . Analysis of the nervous system is simplified by the fact that the thoracic and abdominal segments are mostly alike and thus, a large part of the nervous system called ventral nerve cord represents an array of repeated and almost identical neuromeric units. Currently, the identity and the lineage of all neuroblasts are known and by the end of embryogenesis about 650 neurons and 65 glial cells are found in each neuromer of the ventral nerve cord . The brain lobes of the Drosophila larvae originate from somewhat less well-defined head neuroblasts . The neuronal circuits established by the many neurons in the larval brain are currently being deciphered by analyzing serial TEM sections of a larval brain . Thus, it can be anticipated that within the next years the complete anatomical building plan of the larval nervous system is known.

    Modulation Of The Bbb Following Hypoxia/ischemia And In Stroke

    In vivo and in vitro stroke models have shown that cerebral vascular permeability increases in a time- and hypoxia-dependent manner. This leads to a subsequent increase in cerebral edema however, the processes involved in the hypoxia-induced BBB permeability are not completely understood. Work in animal models of stroke has identified that there is a biphasic leakage of the BBB, with an early opening within hours following hypoxia/ischemia, followed by a refractory phase and then a second opening the next day . In addition, analysis in transgenic models has identified that there are stepwise alterations in the BBB, with an increase in transcytosis observed first followed by alterations in the TJs . There are also important changes in ion channel and efflux transporter expression and activity.

    Molecular Alterations of the Tight Junctions

    Changes in junctional structure formation or stability are now known to involve up-regulation in vascular endothelial growth factor , and inhibition of VEGF attenuates the hypoxia-induced increase in BBB permeability . In addition, hypoxia increases nitric oxide release by ECs and inhibition of NO synthase reduces the effect of hypoxia on cell permeability. Although the exact mechanisms involved in the VEGF- and NO-mediated changes in EC permeability are still being investigated, some reports have shown that NO may directly modify the TJ proteins by nitrosylation or nitrosation.

    MMPs and the BBB

    Modulation of Channels and Transporters

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    Glial Cells And Their Function In The Adult Brain: A Journey Through The History Of Their Ablation

    • 1Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany
    • 2MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
    • 3Munich Cluster for Systems Neurology, Munich, Germany
    • 4Molecular and Translational Neuroscience, Department of Neurology, University of Ulm, Ulm, Germany

    Types Of Neuroglia In The Cns/pns

    Blood Brain Barrier, Animation
    • Produce the myelin sheaths around PNS axons
    • A.& nbsp
    • Oligodendrocytes

  • 2. Have few processes and produce a myelin sheath in CNS each can myelinate parts of several axons
  • A.& nbsp
  • Schwann Cells

  • 3. Small, phagocytic neuroglia that produce the nervous system by engulfing microbes and removing debris of dead cells
  • A.& nbsp
  • Star-shaped cells that perform several functions in support of neurons
  • A.& nbsp
  • Schwann cells

  • 5. Line the brain ventricles and the central canal of the spinal cord they secrete and aid in the circulation of cerebrospinal fluid and they form the blood-cerebrospinal fluid barrier
  • A.& nbsp
    • Sample QuestionThis is the job of the nervous system:To send messages to and from the brain and spinal cord to and from the body.To break down food to be used by the body.To remove wastes from the body.
    • Sample QuestionThe threshold level of a neuron to the minimum stimulus required toOpen potassium gates

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    Which Neuroglia Forms Blood

    There are four types of neuroglia found within the central nervous system: Astrocytes maintain the blood brain barrier and preserve the chemical environment by recycling ions and neurotransmitters. Oligodendrocytes myelinate axons in the central nervous system and provide an overall structural framework.

    When Do We Need To Get Through It

    The bloodbrain barrier is generally very effective at preventing unwanted substances from accessing the brain, which has a downside. The vast majority of potential drug treatments do not readily cross the barrier, posing a huge impediment to treating mental and neurological disorders.

    One possible way around the problem is to trick the bloodbrain barrier into allowing passage of the drug. This is the so-called Trojan horse approach, in which the drug is fused to a molecule that can pass the bloodbrain barrier via a transporter protein.

    A different approach is to temporarily open the bloodbrain barrier using ultrasound.

    In a mouse with Alzheimers disease, we showed that using ultrasound to open the bloodbrain barrier can improve cognition and decrease the amount of toxic plaque that accumulates in the brain. We think this may be due to the ability of ultrasound, in combination with injected gas microbubbles, to temporarily and safely open up the bloodbrain barrier to let protective blood-borne factors in. Importantly, this approach didnt damage the brain.

    In a new study, we have shown that by temporarily opening the bloodbrain barrier, ultrasound allows more of a therapeutic antibody into the brain, improving Alzheimers-like pathology and cognition more than when using ultrasound or the antibody drug in isolation.

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