Blood Brain Barrier Permeation

Jouyban, Abolghasem; Soltani, Somaieh

doi:10.5772/20360

Cited by 12 publications

(12 citation statements)

References 35 publications

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“…2). Among the common ligands that brain endothelial cells internalize by receptor-mediated endocytosis are insulin, Fe 31bound transferrin (or holotransferrin) and low-density lipoprotein (LDL) (Jouyban and Soltani, 2012;Redzic, 2011;Saunders et al, 2013;Smith and Gumbleton, 2006). Receptor-mediated endocytosis in the BBB endothelium primarily takes place at clathrin-coated pits and to a lesser extent at caveolae.…”

Section: Transcellular Versus Paracellular Transport Across the Bbbmentioning

confidence: 99%

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Bock

Haver

Vandenbroucke

et al. 2016

Glia

128

100

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Efficient neuronal signaling in the central nervous system strictly depends on a well-balanced microenvironment around glial cells, synapses, and axons. Unique features of the blood-brain barrier (BBB) endothelium largely determine the composition of this micro-milieu and are dependent on the tight interplay with surrounding astrocytes and pericytes. BBB endothelial cells are endowed with a highly restrictive junctional complex that occludes the intercellular cleft, thereby preventing paracellular diffusion. The paracellular pathway is subject to extensive research as integrity loss of the junctional complex is associated with many neuropathologies, inflammation, and edema. Another important feature of the BBB endothelium is the low prevalence of nonspecific, transcytotic events, including (macro)pinocytosis, clathrin-dependent and caveolin-dependent endocytosis and the subsequent trafficking of vesicles to the opposite membrane. Although less studied, evidence is accruing that this pathway importantly contributes to increased BBB permeability, often when the junctional complex remains intact. Here, we review current knowledge on the contribution of the transcellular pathway to the BBB leak observed in different pathologic conditions. In addition, we hypothesize that nonselective, large pore connexin and pannexin channels may contribute to transcellular transport, either by providing a direct diffusion pathway across the endothelial monolayer, or indirectly, by exerting control over intracellular levels of the signaling ion Ca(2+) that is involved in many steps of the vesicular pathway. We conclude that transcytotic events at the BBB, despite being less acknowledged, cannot be simply dismissed as done in the past, but actively contribute to BBB leakage in many different pathologies. GLIA 2016;64:1097-1123.

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Section: Transcellular Versus Paracellular Transport Across the Bbbmentioning

confidence: 99%

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Bock

Haver

Vandenbroucke

et al. 2016

Glia

128

100

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“…On the other hand, since the charge density on the electrode surface increases upon polarization, charge-dipole interactions between ACC surface and the aromatic acids with permanent dipoles continue to be operative in an enhanced manner. The dipole moments of NA, PA and BA are 3.05 D [22], 2.59 D [23] and 1.21 D [24], respectively. They follow the same order as active fractions.…”

Section: Samplementioning

confidence: 99%

Structural effects on electrosorptive behavior of aromatic organic acids from aqueous solutions onto activated carbon cloth electrode of a flow-through electrolytic cell

Bayram¹,

Ayrancı́²

2012

Journal of Electroanalytical Chemistry

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“…The consistent finding in QSAR modelling shows that lipophilicity is positively correlated, PSA is negatively correlated, hydrogen bonding is negatively correlated, and molecular size (or molecular weight) is negatively correlated to permeability. [6][7][8][9][10][11][12][13][14] There is some evidence that molecular volume might show a parabolic relationship to permeability, since a smaller volume positively increases diffusion, but a larger molecular volume might also increase lipophilicity, which is positively correlated with permeability. [14] 5) The order of permeability appears to be active uptake compounds > passive diffusion compounds > efflux compounds (by about one logPS unit in each case), and the effect of molecular charge for logPS passive diffusion was basic compounds > neutral compounds > acidic compounds.…”

Section: )mentioning

confidence: 99%

“…Recent work has shown that many of the higher molecular weight (volume) permeants utilize active transport mechanisms, such that true passive diffusion is not common. [1][2][3][4][5][6]8,38] The characteristics of the BBB itself clearly are dominant in any mechanistic considerations of permeability by drugs or other compounds such as amino acids, etc.…”

Section: )mentioning

confidence: 99%

“…Statistical (multiple linear regression) quantitative structure activity relationships (QSAR) models: The major descriptors [6][7][8][9][10][11][12][13][14] found to be important in QSAR models (which predominantly seek correlations with logBB) are: 1) Lipophilicity usually expressed as ClogP, has been found to be a critical factor relating to permeability. ClogP has a median value of 2.5 for successful CNS drugs.…”

Section: Introductionmentioning

confidence: 99%

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Permeability of the Blood–Brain Barrier: Molecular Mechanism of Transport of Drugs and Physiologically Important Compounds

Fong¹

2015

J Membrane Biol

115

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A new molecular model for the permeability of drugs and other physiologically important compounds to cross the blood-brain barrier has been developed. Permeability (log PS) is dependant on desolvation, lipophilicity, molecular volume and dipole moment. Previous models for BBB permeability have not considered desolvation and dipole moment as critical factors. The model applies to passive diffusion processes, and some facilitated diffusion processes. Passive permeability models may not apply to active transport processes, where complex membrane protein binding processes (e.g. stereoselectivity) are involved. Model phosphatidylcholine lipid bilayer membranes have been used to evaluate how charged or polar neutral compounds can interact through their molecular dipoles with the cell membrane to induce electromechanical changes in the cell membrane which facilitate permeation. The free energy of solvation in n-octanol has been shown to be a good measure of membrane lipophilicity by calculating the solvation free energy of a model PC lipid membrane in a series of closely related alcohols. The passive diffusion model for alcohols correlates with the known modulation of membrane bilayers which showed a size-dependent "cut-off" point in potency. For most drugs and related molecules, the neutral species are the permeating species.

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Blood Brain Barrier Permeation

Cited by 12 publications

References 35 publications

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Into rather unexplored terrain—transcellular transport across the blood–brain barrier

Structural effects on electrosorptive behavior of aromatic organic acids from aqueous solutions onto activated carbon cloth electrode of a flow-through electrolytic cell

Permeability of the Blood–Brain Barrier: Molecular Mechanism of Transport of Drugs and Physiologically Important Compounds

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