An Experimental Study of Disorders in the Permeability of the Cerebral Vessels (“the Blood‐Brain‐Barrier”) Produced by Chemical and Physico‐chemical Agents
Authors: BROMAN TORE , LINDBERG‐BROMAN A. M. 
Published: December 2008

The permeability of the cerebrospinal vessels has a specific characteristic – the existence of a so‐called blood‐brain‐barrier (BBB). Lesions of the vessels, causing a disorder of the barrierfunction, can be demonstrated by a colour indicator method: Certain dyes, e. g. trypan blue, which cannot normally penetrate the vascular wall, are observed to pass, when the barrier‐function is deranged.

The present investigation is designed to be a crude survey of the disorders of the barrier‐function elicited by some chemical and physico‐chemical agents. The experiments have been performed on guinea‐pigs, rabbits and cats. After the different ways in which the substances have been made to act on the cerebral vessels the experiments have been arranged into three series:

Series 1: Injection into the circulating blood in a cerebral artery; effective concentration unknown due to dilution; post mortem control of the passage of the dye.

Series 2: Local application on the pial vessels; effective concentration known; control in vivo of the passage of the dye.

Series 3: Perfusion during a short period of time (usually 1 min.) of the cerebral vessels with a test‐solution; effective concentration known; control of the passage of the dye in vivo (inspection of the pial vessels) and post mortem.

For practical reasons the tested substances have been allowed to exert their influence only for a short period of time. This undoubtedly represents a source of error when estimating the injurious minimum concentrations.

The fact that the noxious substances disturb the barrier‐function in significantly lower concentrations if administered on the intimaside of the vessels than on the adventitia‐side agrees with the conception of the intima membrane as the site of the permeability – including the BBB‐function.

It is obvious that certain substances have an injurious influence on the nerve cells in concentrations below those needed for disturbing the barrier‐function. That applies to hypotonic salt solutions (aq. dest. in short‐time experiments) and to ethyl alcohol. Other substances seem first to destroy the vascular membrane, thereby causing secondary lesion of the nervous tissue. That appears to apply to cobra venom and to sheep‐hemolytic rabbit serum in experiments with guinea‐pigs.

Changes of the osmotic pressure and of the hydrogen ion concentration cause a disorder of the barrier‐function only if they are fairly great. From a methodological point of view this is of value in experiments with other substances.

The negative results in experiments with histamine as well as the positive results in those with bile salts and ethyl alcohol may have a certain clinical interest.

It seems probable that proteins (toxins, venoms, antigens) cannot pass from the blood into the normal brain, if they do not exert a toxic influence on the vessels. A disturbed permeability may then render their passage possible (if they are still circulating in the blood), but is in itself reason enough for a secondary injury to the brain tissue.

A local allergic reaction in the brain with disturbance of the barrier‐function can seemingly be produced by antigens such as horse serum only if they are injected intracerebrally, thus causing a mechanical injury, which allows a passage of antibodies from the blood into the brain. In the FORSSMAN‐SKOOG‐experiments a cercbral lesion of probably allergic origin (reverse allergy) is also elicited. Our experiments have shown, however, that this lesion is not caused by a simple reaction between the injected antibodies and the vascular endothelium, but that the blood corpuscles of the animal must contain a third factor necessary for the reaction.