The blood-brain barrier to horseradish peroxidase under normal and experimental conditions

Abstract

This review paper deals with the transport of the protein tracer horseradish peroxidase across cerebral vessels under normal and various experimental conditions. Electronmicroscopical investigations have revealed that, under normal conditions, a minor vesicular transfer of intravenously injected peroxidase occurs across the endothelium in segments of arterioles, capillaries and venules, especially in arterioles with a diameter about 15-30 mu. This normally occurring vesicular transport is susceptible to various experimental conditions. Thus the transfer of tracer increases when a hypertonic solution is injected into the internal carotid artery presumably due to vesicular transport. Extensive acute hypertension of short duration also increases the vesicular transfer of peroxidase from blood to brain. Identical observations are obtained when the hypertension is evoked by intravenous injection of phentolamine and by electrically induced seizures. During the postischemic period, one hour after release of the occlusion of an internal carotid artery in the Mongolian gerbil the vesicular transport of peroxidase is increased across the endothelium of cerebral vessels. The explanation may be release of serotonin from blood platelets during the occlusion. The serotonin could then increase the blood pressure locally in the brain resulting in an enhanced permeability. Serotonin, after perfusion through the cerebral ventricular system, is also able to increase the normally occurring vesicular transfer. The most likely mechanism behind this phenomenon seems at the moment to be local hypertension evoked by serotonin-induced vasoconstriction of arterioles. Finally, the enhanced vesicular transport across cerebral endothelium caused by porto-caval anastomosis is mentioned and the possible role of disturbances in the metabolism of amines as responsible for the extravasation is discussed.