Permeability of Blood-CNS Barrier in Experimental Poliomyelitis as Determined by the Nitrate Test. ∗

Abstract

The concentration of any substance in the cerebrospinal fluid depends to a large extent upon its concentration in the blood, the passage of such substances between these 2 systems being controlled by a mechanism frequently referred to as the blood-brain barrier. Since variations in barrier permeability patently affect the interchange of constituents of the 2 systems, a number of tests have been devised for measuring alterations in barrier permeability in central nervous system disturbances. One such test is that of Mestrezat and Gaujoux, 1 which depends on the passage of nitrate into the cerebrospinal fluid after its oral administration in the form of sodium nitrate. Mestrezat 2 believes that a high barrier permeability indicates menin-geal inflammation. Katzenelbogen 3 states that inflammatory processes within the cerebrospinal canal, as evidenced by pleocytosis and increased protein in the spinal fluid, are frequently associated with high barrier permeability for nitrate, although an increased permeability may occasionally be found in cases with a normal fluid.

To determine if changes in barrier permeability occur in experimental poliomyelitis, we employed a modification of the nitrate test, administering the nitrate intravenously rather than orally. Rhesus monkeys (Macaco, mulatto) in the preparalytic or paralytic stages of poliomyelitis following intranasal or intracerebral inoculation of the potent MV strain of virus constituted the test group, normal and poliomyelitis convalescent monkeys serving as controls. Each animal received intravenously 35 mg. of sodium nitrate per kilo of body weight one hour before cisternal puncture. Every specimen of spinal fluid was tested for globulin by Pandy's method, and the cell content determined. Standard solutions of sodium nitrate containing from 10 mg. to 100 mg. per 1000 cc. were prepared from a 1% stock solution. In performing the test, 2 cc. of Merck's reagent sulfuric acid (NO₃ content 0.0002%) was pipetted into the bottom of clean serological tubes and overlaid with 0.2 cc. of 1% diphenylamine in 75% sulfuric acid.