Thursday, May 19, 2022

How Does The Blood Brain Barrier Work

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Choosing A Magnesium L

Blood Brain Barrier, Animation

Very few magnesium supplements contain magnesium l-threonate.

So you must check product labels carefully to make sure your supplement contains it.

Magnesium l-threonate is available in its generic form, but there is one brand name you can look for as well, Magtein.

Magtein

Magtein is a patented form of magnesium l-threonate thats been well-studied in animals.

Magtein is a raw ingredient included in magnesium formulations from a handful of supplement companies including Jarrow Formulas, NOW, and Source Naturals.

Dr. Pat | Be Brain Fit

The company behind Magtein partnered with Stanford University in one clinical trial, The Use of Magnesium L-Threonate for the Enhancement of Learning and Memory in People With Mild to Moderate Dementia.

You can read about it on ClinicalTrials.gov, a database of clinical trials being conducted around the world.

The fact that this brand name product has been studied does not necessarily mean it is more effective than generic magnesium l-threonate.

In my opinion, this simply reflects the monetary reality that there is little incentive for companies to conduct studies on substances that cant be patented.

Expression Of Glut1 In Brain Is Localized To The Bloodbrain Barrier

Predicted secondary structure of the bovine bloodbrain barrier GLUT1 glucose transporter is shown, which is formed by 12 transmembrane domains, a glycosylated extracellular loop between transmembrane domains 1 and 2, and intracellular amino and carboxyl termini. Northern blot of mRNA derived from either total rabbit brain or capillary-depleted rabbit brain for either the GLUT1 glucose transporter or actin. Electron microscopic immunogold study of human brain with a primary antiserum against the purified human erythrocyte glucose transporter, and a secondary antibody conjugated with 10nm gold particles, shows abundant expression of immunoreactive GLUT1 glucose transporter on the luminal and abluminal membranes of the capillary endothelium in human brain.

How Do We Know Vaccine Components Dont Cross The Bbb

Vaccines contain versions of a pathogen that are different than the ones that cause disease. Many vaccines do not contain live pathogens, but rather pieces of pathogens. As such, they do not replicate and, therefore, cannot cause infections or damage to the BBB. Live, weakened vaccines replicate a very limited number of times, so the tissue damage that can result during an infection does not occur. Therefore, the BBB is not damaged by vaccines instead, vaccines lead to protective immune responses that prevent infections and, therefore, the damage that can result from these infections.

Some people wonder not about the pathogens in vaccines, but rather other components of vaccines:

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Issues Surrounding The Bbb

Poor Drug Transport From Cerebrospinal Fluid To Brain

How Does the Brain Sense Osmolality?

Film autoradiogram of rat brain section 20 hours after the injection of -BDNF into the lateral ventricle . Solute distribution into brain parenchyma from the cerebrospinal fluid compartment is limited by the slow rate of solute diffusion from the ependymal surface, relative to the rapid rate of bulk flow of CSF from the ventricles to the systemic circulation across the arachnoid villi. Logarithmic decrease in the brain concentration of glial-derived neurotrophic factor in the brain of the Rhesus monkey relative to the distance from the intracerebral catheter used for brain drug delivery with convection-enhanced diffusion.

In addition to the macrocirculation of CSF through the ventricular system, there is a CSF microcirculation through the Virchow-Robin compartment, which is formed by the perivascular space around penetrating cortical precapillary arterioles, which emanate from the pial vessels on the surface of the brain. However, the fluid flow via the microcirculation is quantitatively small compared with the CSF macrocirculation. The rate of flow of the CSF macrocirculation is 2L/min in the rat, whereas the rate of flow of the Virchow-Robin microcirculation is only 5% of the CSF flow rate, or 0.1L/min in the rat.

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Discovery Of Bloodbrain Barrier Receptor

Light micrograph of freshly isolated bovine brain capillaries stained with trypan blue, which stains nuclei blue and luminal red blood cells yellow. The capillaries are isolated free of adjoining brain tissue. Schematic diagram of different brain endothelial receptors, including the insulin receptor, the transferrin receptor, the scavenger receptor , which mediates only the endocytosis from blood into the endothelial compartment for ligands such as acetylated low density lipoprotein and the neonatal Fc receptor , which mediates the asymmetric transcytosis of IgG molecules selectively from brain to blood, but not blood to brain. Confocal microscopy of isolated rat brain capillaries showing the expression of the Tf receptor on both luminal and abluminal membranes of the endothelium. Light micrograph of rat brain removed after a 10-minute carotid artery infusion of a conjugate of 5nm gold and the mouse OX26 monoclonal antibody against the rat TfR. The staining of the capillary compartment represents TfRMAb present in the intraendothelial compartment of the brain. Electron microscopy of rat brain after perfusion with the conjugate of gold and TfRMAb shows the MAb concentrated in intraendothelial vesicles , as well as MAb molecules undergoing exocytosis from the endothelial compartment to the brain interstitial space .

Active Efflux Transporters And Enzymatic Bloodbrain Barrier

The active efflux transporters serve to mediate the asymmetric efflux of metabolites and drugs from the brain to blood. The classical AET system within the BBB is p-glycoprotein, which is a product of the MDR gene, MDR1, also named the ABC subfamily B member 1 . Apart from p-glycoprotein, there are numerous other members of the ABC gene family of transporters that are expressed at the BBB, and these have been quantified by Terasaki and coworkers. The AET systems may work in concert with enzymes expressed within the BBB, such as P450 enzymes. Both the AET systems, and the enzymatic barriers are subject to modulation. Bloodbrain barrier p-glycoprotein activity is suppressed by vascular endothelial growth factor, and the CYP1A1 and CYP1B1 P450 enzymes are upregulated by environmental toxins, such as dioxin derivatives, which activate the aryl hydrocarbon receptor at the BBB. In addition to environmental toxins, or growth factors, BBB permeability may be altered by disease states, including aging.

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Introduction To The Blood

The blood-brain barrier is a component of the neurovascular unit and acts as the blood-brain interface, mediating communication between the central nervous system and the periphery. The BBB separates the circulation from the brain, allowing for protection from and transport regulation of serum factors and neurotoxins. The BBB is not just a physical barrier but also acts more selectively as a transport interface , a secretory body, and a metabolic barrier .

What Is Blood Pressure

How is the blood brain barrier affected by Alzheimers disease?

Blood pressure is the vital force that propels oxygen-rich blood to all parts of your body. Your heart is the pump that generates the force, and your arteries are the channels that transport and distribute the blood.

The height of your blood pressure is determined by how forcefully your heart’s main pumping chamber, the left ventricle, contracts, and by the diameter and stiffness of your arteries. In turn, your heart and arteries are influenced by a large number of genetic, hormonal, metabolic, neurological, psychological, and lifestyle factors that determine your blood pressure. Because these influences are so numerous and complex, your blood pressure can vary from minute to minute and hour to hour during the course of the day, to say nothing of the slower shifts that occur over the course of a lifetime.

Blood pressure has two components. Your systolic blood pressure is the higher number, recorded while your heart is pumping blood into your arteries your diastolic blood pressure is the lower number, recorded when your heart is relaxing and refilling with blood between beats. Both numbers are calibrated in millimeters of mercury , a vestige of the mercury column used in the first pressure manometers more than 100 years ago. By convention, the higher number is recorded first a systolic pressure of 110 mm Hg and diastolic pressure of 70 mm Hg would be written as 110/70 and pronounced “110 over 70.”

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Insulin Signaling Within Cells Of The Blood

There is not a cell type in the CNS that we are aware of that does not express the insulin receptor. In mice, the expression of the insulin receptor gene is most abundant in endothelial cells, about two times greater than astrocytes, with neurons falling in close behind in terms of RNA expression levels1 . This same expression pattern was not observed in samples from human tissue . Instead, expression of the insulin receptor is more evenly distributed between the cell types. Insulin interacts with receptors on neurons and glial cells , endothelial cells , and pericytes to elicit various physiological effects, some of which are highlighted in Figure 1. The insulin receptor exists in two isoforms, an A and B form, due to differences in splicing of the subunit, resulting in different binding affinities to insulin and insulin-like growth factor . However, until recently, the ability to detect these two isoforms by immunological methods in vivo in different cell types has been a challenge. With the advances in single cell RNA sequencing and a novel in situ RT-PCR/FISH assay , we expect a growth in the knowledge of expression pattern of these isoforms and alterations in human disease within specific cell types and regional variations. The insulin receptor can also form heterodimers with the IGF-1 receptor and can have varying post-translational modifications leading to further diversity of insulin action .

Drug Transport Into Brain Via Bloodbrain Barrier Carrier

-DOPA, gabapentin, paraquat, and melphalan are examples of BBB delivery via LAT1 of drugs that have structures that mimic the endogenous substrate, neutral amino acids. An alternative approach is to conjugate a drug, which normally does not cross the BBB, with a CMT substrate, for example, glucose, that does cross the BBB. This was attempted with oligopeptides, which were conjugated with glucose. However, the glucose moiety of the glycopeptide no longer was transported via GLUT1. Instead, the structure of the CMT substrate must be retained following conjugation of the nontransportable drug. This is possible with ingenious uses of medicinal chemistry as applied to BBB structuretransport relationships. A novel example is the case where a nontransportable drug is coupled to the thiol group of -cysteine. Cysteine is a small neutral amino acid, which has a low affinity for LAT1. However, when the drug is conjugated to the thiol group of cysteine, the small neutral amino acid is converted into a large neutral amino acid, and significant BBB transport via LAT1 was observed. This case shows that a CMT substrate can be used as a drug carrier, providing the original structural characteristic of the substrate class for the targeted CMT system is retained.

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What Is Magnesium L

Magnesium l-threonate is the latest magnesium chelate.

It was developed by a team of neuroscientists at Massachusetts Institute of Technology and Tsinghua University in Beijing who bound magnesium to l-threonate, a vitamin C metabolite.

” Magnesium l-threonate readily crosses the brains protective filter, the blood-brain barrier, to get into the brain where it is needed.

There is no reason to be concerned that magnesium l-threonate is not natural.

When it comes to magnesium supplements, natural is not necessarily better.

Magnesium sulfate naturally occurs in Epsom salts, but its a harsh laxative thats barely absorbed and has a lot of potential side effects.

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This makes it one of the worst forms of magnesium that you can take, especially if improving brain function is your goal.

You may already be familiar with popular magnesium supplements like magnesium citrate and magnesium glycinate.

They too are synthesized in a laboratory.

Protective Coverings Of The Brain And Spinal Cord

Blood brain barrier, blood brain barrier function &  cells

The outer surface of the CNS is covered by a series of membranes composed of connective tissue called the meninges, which protect the brain. The dura mater is a thick fibrous layer and a strong protective sheath over the entire brain and spinal cord. It is anchored to the inner surface of the cranium and vertebral cavity. The arachnoid mater is a membrane of thin fibrous tissue that forms a loose sac around the CNS. Beneath the arachnoid is a thin, filamentous mesh called the arachnoid trabeculae, which looks like a spider web, giving this layer its name. Directly adjacent to the surface of the CNS is the pia mater, a thin fibrous membrane that follows the convolutions of gyri and sulci in the cerebral cortex and fits into other grooves and indentations .

Figure 14.2.4 Meningeal Layers of Superior Sagittal Sinus:

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If Found Effective Who Will This Approach Help

Breaching this barrier opens up a new frontier in treating the brain. The success of this research opens up the potential for delivering drug therapies to parts of the brain protected by the BBB, including researching treatments for patients with various kinds of brain tumours, Alzheimers disease, and some psychiatric conditions.

Why Would Anyone Want To Break It

The BBB has been a persistent obstacle to delivering valuable medication therapies to treat diseases of the brain such as tumours and various types of neurological disorders because of its plastic wrap layer around the blood vessels.

Some medications can get through this BBB but it can vary from zero percent to a small amount. For example, some chemotherapy has up to a 20 per cent chance of reaching these parts of the brain because of the BBB.

Researchers are hoping that by temporarily and safely opening this barrier in a patient to deliver medication directly to the brain tumour, it may potentially mean providing more targeted treatment in the future, which they think will require less medication, leave fewer side effects and improve quality of life.

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Dysfunction Of The Bbb In Cns Disorders

Disruption of the BBB is observed in many different neurological disorders including MS, stroke, Alzheimer’s disease , epilepsy, and traumatic brain injuries. Functional imaging of human patients and analysis of postmortem brain samples has identified the pathological breakdown of the barrier in different neurological diseases. In addition, work with animal models of disease and with cell culture BBB models has enabled the identification of some of the molecular mechanisms that cause changes to the BBB. This dysfunction can include alterations in many different properties of the BBB including TJs, transporters, transcytosis, and LAM expression. This breakdown can lead to edema, disruption of ionic homeostasis, altered signaling, and immune infiltration that can lead to neuronal dysregulation and, ultimately, degeneration. Although BBB dysfunction is often secondary to the primary insult in these diseases, in some cases, it has been a suggested cause, including MS, epilepsy, and AD .

Schematic representation of signaling regulating the bloodbrain barrier in health and disease. ICAM, intercellular adhesion molecule MMP, matrix metalloproteinase ROS, reactive oxygen species.

Why You Should Consider Taking More Than One Form Of Magnesium

The link between the gut microbiome and the blood-brain barrier

This low amount of elemental magnesium indicates that magnesium l-threonate is not a good choice for overcoming an overall magnesium deficiency.

For that, better choices are magnesium glycinate, gluconate, or citrate.

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Theres no reason you cant take more than one kind of magnesium.

In fact, many formulations cover all bases by including more than one form.

Youll know if youve overdone it with magnesium loose stools are the telling sign.

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What Is The Blood Brain Barrier

Each person has a protective blood barrier lining the blood vessels in the brain to restrict the passage of large toxic substances from the bloodstream into the brain.

You can imagine the barrier acting like plastic wrap around the small blood vessels. In most areas of the body, there is no plastic wrap and whatever is in the bloodstream can get into the various tissues of the body, such as muscle, etc.

In the brain, all of the blood vessels have this plastic wrap around them that only allows very select molecules to get through.

Protect The Brain Against Neurotoxins

Many potential neurotoxins are circulating in our blood, including those from endogenous sources such as metabolites or proteins, or exogenous ones such as xenobiotics ingested in the diet or otherwise acquired from the environment. The BBB function is to regulate the entry of different circulating substances based on CNS needs. The transport barrier represented by multiple ABC energy-dependent efflux transporters occupies the BBB luminal surface. It actively pumps many of these agents out of the brain . The adult CNS has a limited regenerative capacity if damaged, and fully differentiated neurons have a minimal ability to divide and replace themselves under normal circumstances. There is a continuous steady rate of neuronal cell death from birth throughout life in the healthy human brain, with relatively low levels of neurogenesis . That is why any factor promoting an acceleration of the natural rate of cell death would become prematurely debilitating.

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