The Blood-Brain Barrier-Why the Brain Dies First

To the Editor:—  The medical literature relating to the blood-brain barrier contains relatively little on the probable role of plasma protein in this phenomenon. My interest in the osmotic behavior of the protein molecule began in 1932¹ when experiments were undertaken in an attempt to explain the latent interval that characterizes the syndrome of chronic subdural hematoma. These tests showed that measured amounts of the animal's blood contained in a cellophane sac increased in volume when immersed in cerebrospinal fluid or when placed beneath the dura. This effect was attributed to the osmotic tension of plasma protein acting across a membrane impermeable to this molecule.A point frequently overlooked is the difference between osmolality and osmotic tension. As succinctly pointed out by Doemling,² relative osmolality concerns only the total concentration of osmotically active molecules or ions on the two sides of an interposed membrane, while relative tonicity concerns