Habgood, Mark David (1990) Barriers in the developing brain. University of Southampton, Doctoral Thesis.
Abstract
The subject of this thesis is broad and concerns the effects of an elevated arterial PCO2 (hypercapnia) on the permeability properties of developing and mature barriers within the brain. Hypercapnia produces a reversible, graded increase in CSF:plasma and brain:plasma ratios for a number of lipid insoluble test compounds ranging in size from sucrose (0.5 nm molecular radius) to IgG (5.3 nm). These apparent increases in barrier permeability cannot be fully accounted for by changes in cerebral blood flow, or by changes in cerebral blood pressure. The effects of pH on barrier permeability remain unclear, but may be important and require further investigtion as a possible mechanism underlying the effects of hypercapnia. The developing blood-CSF barrier in two day old rats is affected by hypercapnia in a remarkably similar way to that of the adult animal. The major difference being that the stady state CSF:plasma ratios attained in two day old rats are higher than in the adult rat. It is possible that differences in the CSF-sink effect at this age may underlie the differences between newborn and adult animals. There was no evidence of a `leaky' or immature blood-CSF barrier in the newborn rat. The experiments on hypercapnia, highlighted a much greater penetration of albumin into the CSF of newborn rats, and fetal 60 days gestation sheep compared to other lipid insoluble compounds. Evidence is presented to show that in the developing brain, albumin is probably transported across the blood-CSF barrier by a specific transfer mechanism that can distinguish between different species of the same protein.
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