PMC:6194691 / 74482-77895
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/6194691","sourcedb":"PMC","sourceid":"6194691","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6194691","text":"Water\nWater permeability of the blood–brain barrier can be calculated in two very different ways. In the first tritiated water is introduced into the blood and the permeability, Pw,tracer calculated from the ratio of the undirectional influx of tracer, Jinf, to the concentration of the tracer, cTHO,7 Pw,tracer=Jinf/cTHO.\nIt is assumed that this permeability also applies to efflux and to unlabelled water. This permeability is often called the diffusional water permeability, Pd. The major difficulty with this method is that the influx is so great that 70–90% of the tracer arriving in the blood enters the parenchyma in a single pass (see chapter 4 in Bradbury [55] and [283–289]). Thus along much of the length of the microvessels the concentration gradient of the tracer across the microvessel walls driving its influx is much less than the concentration that was added to the blood. The permeability calculated from Eq. 7 using the arterial concentration of the tracer thus seriously underestimates the true water permeability of the blood–brain barrier. Mathematical expressions to correct for this effect have been derived relating the fraction of the tracer extracted from the flow through the blood vessel to the PS product (reviewed in [159]). However, even after correction the calculated values are inaccurate when the extraction fraction is large. Paulson et al. [290] found values about 1/5th of the PS values calculated from osmotic flow as described below and similar values have been determined by others (see [159]).\nThe second method for measuring water permeability uses an osmotic gradient to generate a net flux, Jnet, of water across the barrier. In effect a water concentration gradient is produced by “diluting” or “concentrating” the water on one side by adding or removing solutes and the permeability is then calculated as8 Pw,osmotic=Jnet/Δcwith results close to 1.1 × 10−3 cm s−1 for both rats [291, 292] and humans [290]. (The original references and a recent review [4] can be consulted for the actual equations used which are based on arguments that avoid the rather woolly concepts of “diluting” and “concentrating” the water). Using S = 100 cm2 g−1, the value of the surface area of the microvessels employed in [290, 292], the permeability-area product, PS, i.e. the clearance, is ~ 0.11 mL g−1 s−1 = 6.7 mL g−1 min−1. Patlak and Paulson [293] have argued that for the blood–brain barrier the tracer value is likely to be a better estimate of the true water permeability because the measurement of osmotic permeability using a brief exposure to raised osmolality reflects partly water extraction from the endothelium rather than from the parenchyma. It is adequate for the present purpose to use the two estimates as brackets of the correct value.\nWater influx and efflux across the human blood–brain barrier each amount to roughly 40,000 mol day−1. The difference between the influx and efflux is very much less. Not even the normal direction of the net flux of water across the blood–brain barrier is known with any certainty, partly because it is so small. The available evidence suggests that scaled for a human there is a net movement from blood to brain amounting perhaps to ~ 10 mol day−1 (see [4]). For comparison metabolic production of water within the brain is ~ 3.3 mol day−1 and the amount of water in the CSF produced by the choroid plexuses is ~ 28 mol day−1.","divisions":[{"label":"title","span":{"begin":0,"end":5}},{"label":"p","span":{"begin":6,"end":322}},{"label":"label","span":{"begin":300,"end":301}},{"label":"p","span":{"begin":323,"end":1537}},{"label":"p","span":{"begin":1538,"end":2786}},{"label":"label","span":{"begin":1853,"end":1854}}],"tracks":[{"project":"MyTest","denotations":[{"id":"30340614-14939058-30706208","span":{"begin":676,"end":679},"obj":"14939058"},{"id":"30340614-4925747-30706208","span":{"begin":676,"end":679},"obj":"4925747"},{"id":"30340614-4419687-30706208","span":{"begin":676,"end":679},"obj":"4419687"},{"id":"30340614-1146566-30706208","span":{"begin":676,"end":679},"obj":"1146566"},{"id":"30340614-3810751-30706208","span":{"begin":676,"end":679},"obj":"3810751"},{"id":"30340614-859448-30706209","span":{"begin":1380,"end":1383},"obj":"859448"},{"id":"30340614-5921096-30706210","span":{"begin":1928,"end":1931},"obj":"5921096"},{"id":"30340614-859448-30706211","span":{"begin":1950,"end":1953},"obj":"859448"},{"id":"30340614-27799072-30706212","span":{"begin":2002,"end":2003},"obj":"27799072"},{"id":"30340614-859448-30706213","span":{"begin":2251,"end":2254},"obj":"859448"},{"id":"30340614-7207231-30706214","span":{"begin":2378,"end":2381},"obj":"7207231"},{"id":"30340614-27799072-30706215","span":{"begin":3241,"end":3242},"obj":"27799072"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"30340614-14939058-30706208","pred":"source","obj":"MyTest"},{"subj":"30340614-4925747-30706208","pred":"source","obj":"MyTest"},{"subj":"30340614-4419687-30706208","pred":"source","obj":"MyTest"},{"subj":"30340614-1146566-30706208","pred":"source","obj":"MyTest"},{"subj":"30340614-3810751-30706208","pred":"source","obj":"MyTest"},{"subj":"30340614-859448-30706209","pred":"source","obj":"MyTest"},{"subj":"30340614-5921096-30706210","pred":"source","obj":"MyTest"},{"subj":"30340614-859448-30706211","pred":"source","obj":"MyTest"},{"subj":"30340614-27799072-30706212","pred":"source","obj":"MyTest"},{"subj":"30340614-859448-30706213","pred":"source","obj":"MyTest"},{"subj":"30340614-7207231-30706214","pred":"source","obj":"MyTest"},{"subj":"30340614-27799072-30706215","pred":"source","obj":"MyTest"}]},{"project":"2_test","denotations":[{"id":"30340614-14939058-30706208","span":{"begin":676,"end":679},"obj":"14939058"},{"id":"30340614-4925747-30706208","span":{"begin":676,"end":679},"obj":"4925747"},{"id":"30340614-4419687-30706208","span":{"begin":676,"end":679},"obj":"4419687"},{"id":"30340614-1146566-30706208","span":{"begin":676,"end":679},"obj":"1146566"},{"id":"30340614-3810751-30706208","span":{"begin":676,"end":679},"obj":"3810751"},{"id":"30340614-859448-30706209","span":{"begin":1380,"end":1383},"obj":"859448"},{"id":"30340614-5921096-30706210","span":{"begin":1928,"end":1931},"obj":"5921096"},{"id":"30340614-859448-30706211","span":{"begin":1950,"end":1953},"obj":"859448"},{"id":"30340614-27799072-30706212","span":{"begin":2002,"end":2003},"obj":"27799072"},{"id":"30340614-859448-30706213","span":{"begin":2251,"end":2254},"obj":"859448"},{"id":"30340614-7207231-30706214","span":{"begin":2378,"end":2381},"obj":"7207231"},{"id":"30340614-27799072-30706215","span":{"begin":3241,"end":3242},"obj":"27799072"}],"attributes":[{"subj":"30340614-14939058-30706208","pred":"source","obj":"2_test"},{"subj":"30340614-4925747-30706208","pred":"source","obj":"2_test"},{"subj":"30340614-4419687-30706208","pred":"source","obj":"2_test"},{"subj":"30340614-1146566-30706208","pred":"source","obj":"2_test"},{"subj":"30340614-3810751-30706208","pred":"source","obj":"2_test"},{"subj":"30340614-859448-30706209","pred":"source","obj":"2_test"},{"subj":"30340614-5921096-30706210","pred":"source","obj":"2_test"},{"subj":"30340614-859448-30706211","pred":"source","obj":"2_test"},{"subj":"30340614-27799072-30706212","pred":"source","obj":"2_test"},{"subj":"30340614-859448-30706213","pred":"source","obj":"2_test"},{"subj":"30340614-7207231-30706214","pred":"source","obj":"2_test"},{"subj":"30340614-27799072-30706215","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"MyTest","color":"#93ece5","default":true},{"id":"2_test","color":"#eccb93"}]}]}}