The BBB results from the selectivity of the tight junctions between the endothelial cells of brain capillaries, restricting the passage of solutes.[1] At the interface between blood and the brain, endothelial cells are adjoined continuously by these tight junctions, which are composed of smaller subunits of transmembrane proteins, such as occludin, claudins (such as Claudin-5), junctional adhesion molecule (such as JAM-A).[6] Each of these tight junction proteins is stabilized to the endothelial cell membrane by another protein complex that includes scaffolding proteins such as tight junction protein 1 (ZO1) and associated proteins.[6]
The BBB is composed of endothelial cells restricting passage of substances from the blood more selectively than endothelial cells of capillaries elsewhere in the body.[9] Astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the BBB, providing biochemical support to those cells.[10] The BBB is distinct from the quite similar blood-cerebrospinal fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood-retinal barrier, which can be considered a part of the whole realm of such barriers.[11]
Blood-brain Barrier Ppt Download
Download 🔥 https://tiurll.com/2yGcwG 🔥
Measurement of brain uptake of various blood-borne solutes showed that newborn endothelial cells were functionally similar to those in adults,[15] indicating that a selective BBB is operative at birth.
Mechanisms for drug targeting in the brain involve going either "through" or "behind" the BBB. Modalities for drug delivery to the brain in unit doses through the BBB entail its disruption by osmotic means, or biochemically by the use of vasoactive substances, such as bradykinin,[30] or even by localized exposure to high-intensity focused ultrasound (HIFU).[31]
Other methods used to get through the BBB may entail the use of endogenous transport systems, including carrier-mediated transporters, such as glucose and amino acid carriers, receptor-mediated transcytosis for insulin or transferrin, and the blocking of active efflux transporters such as p-glycoprotein.[27] Some studies have shown that vectors targeting BBB transporters, such as the transferrin receptor, have been found to remain entrapped in brain endothelial cells of capillaries, instead of being ferried across the BBB into the targeted area.[27][32]
The first papers modelling blood-brain barrier permeability identified three properties, i.e., molecular volume, lipophilicity, and hydrogen bonding potential, as contributing to solute transport through the blood-brain barrier.[41] A 2022 dataset selected different classification models[42] based on molecular fingerprints,[43] MACCS166 keys[44] and molecular descriptors.[45]
All the while, bacteriologist Paul Ehrlich was studying staining, a procedure that is used in many microscopy studies to make fine biological structures visible using chemical dyes.[49] As Ehrlich injected some of these dyes (notably the aniline dyes that were then widely used), the dye stained all of the organs of some kinds of animals except for their brains.[49] At that time, Ehrlich attributed this lack of staining to the brain simply not picking up as much of the dye.[47]
However, in a later experiment in 1913, Edwin Goldmann (one of Ehrlich's students) injected the dye directly into the cerebrospinal fluid of animal brains. He found then the brains did become dyed, but the rest of the body did not, demonstrating the existence of a compartmentalization between the two. At that time, it was thought that the blood vessels themselves were responsible for the barrier, since no obvious membrane could be found.
The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.
Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood-brain barrier (BBB), blood-CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood-CNS exchange. The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.
The blood-brain barrier (BBB) is a selective semi-permeable membrane between the blood and the interstitium of the brain, allowing cerebral blood vessels to regulate molecule and ion movement between the blood and the brain.[1] The BBB is composed of endothelial cells (ECs), pericytes (PCs), capillary basement membrane, and astrocyte end-feet, all of which aim to shield the brain from toxic substances, filter harmful compounds from the brain to the bloodstream, and supply brain tissue with nutrients. To do this, the BBB has physical (tight junctions) and metabolic (enzyme) barriers.[2] Central nervous system (CNS) structures are unique in structure and function and therefore require a stable environment with a composition that differs from that of the peripheral circulation. For this reason, the BBB exists to maintain a homeostatic environment in which CNS structures can function without disruption from other bodily functions.
As previously mentioned, the blood-brain barrier (BBB) is composed of a capillary basement membrane and three cellular elements: endothelial cells, pericytes, and astrocyte end-feet. The BBB is responsible for creating and maintaining homeostasis for neuronal functions, defending the system against toxic insults, regulating the communication between the periphery and the CNS, and providing the brain with nutrients. This is achieved via four main mechanisms: prevention of the paracellular diffusion of hydrophilic compounds, mediation of the active transport of nutrients to the brain, activation of efflux transport of hydrophobic molecules and drugs from the brain to the blood, and regulation of the transendothelial migration of circulating blood cells and pathogens.[3]
Located between cerebral endothelial cells, TJs form a highly-selective diffusion barrier prohibiting most blood-borne substances from entering the brain. TJs block the paracellular aqueous diffusional pathways between adjacent endothelial cells. Due to their adhesive function, they seal microvessels and impede the passive diffusion of proteins and polar solutes in and out of the CNS.[4]
Astrocyte end-feet ensheath the vessel wall and play a critical role in the induction and maintenance of the TJ barrier. Astrocyte end-feet are not believed to have a barrier function within the mammalian brain.[5]
The ECs of the BBB differ from those of the rest of the body. BBB ECs have no fenestrations, more extensive tight junctions, and sparse pinocytic vesicular transport. EC tight junctions limit the paracellular flux of hydrophilic molecules across the BBB.
Embedded within the capillary basement membrane, PCs play a crucial role in angiogenesis, the structural integrity and differentiation of the microvessels, and the formation of endothelial tight junctions.[6]
The blood-brain barrier is present in all regions of the brain except the circumventricular organs (CVOs), located around the third and fourth ventricles.[7] Blood vessels around the CVOs have fenestrations that permit the diffusion of blood-borne molecules across the vessel wall. These unprotected areas of the brain regulate the autonomic nervous system and endocrine glands. The CVOs are:
The development of the blood-brain barrier begins with angiogenesis, which occurs early in gestation during neural tube development. In angiogenesis, preexisting vessels guided by vascular endothelial growth factor (VEGF) invade a developing neuroectoderm and give rise to new vessels. Downstream VEGF signaling is essential, supporting angiogenesis via endothelial cell proliferation, migration, and survival.[8] These new vessels forming in the neuroectoderm exhibit many properties of the BBB at early stages, including the expression of tight junctions and nutrient transporters that will later play a role in the selectivity of this barrier. These early vessels also contain high levels of transcytotic vesicles and exhibit increased expression of leukocyte adhesion molecules.[9]
Maturation and maintenance of the BBB are accomplished by the persistence of TJ protein expression and their redistribution throughout the BBB structure. Close contact between endothelial cells, astrocytes, and pericytes sustains BBB integrity and function as a stabilized neurovascular unit.[10] The BBB is formed and completely functional by the third trimester of gestation.
Alterations in the development of the BBB and the expression of TJs may potentially lead to anomalies later in life and an increased predisposition to develop metabolic diseases. Maternal obesity increases BBB permeability in offspring, leading to higher exposure to leptin and ghrelin. This increased exposure to leptin and ghrelin can contribute to metabolic defects in adult life, predisposing children to developing metabolic syndrome in childhood or early adulthood.[11]
As previously discussed, the BBB is relatively impermeable under normal physiologic conditions. However, in pathologic conditions, several chemical mediators that increase BBB permeability may be released, including glutamate, aspartate, taurine, ATP, endothelin-1, ATP, NO, MIP-2, TNF-alpha, and IL-beta, which are produced by astrocytes. Other agents that increase BBB permeability include bradykinin, 5HT, histamine, thrombin, UTP, UMP, substance P, quinolinic acid, platelet-activating factor, and free radicals. 152ee80cbc
basic electrical questions and answers pdf download
we will glorify the king of kings mp3 download