Endothelial negative surface charge areas and blood-brain barrier function.

Recent evidence points to the negative surface charge of the luminal endothelial membrane of brain vessels as one determinant for morphologic blood-brain barrier function. The present study evaluates, in awake rats, how barrier function is affected by the polycation protamine to neutralize the negatively charged groups. High local doses of protamine, as infused intracarotideally, are able to substantially impair barrier capacity against albumin and inulin, which normally do not pass the blood-brain barrier. Evidence is presented that it is the positive charge of protamine that is a major factor underlying the barrier opening. However, when comparing the barrier opening obtained by corresponding concentration of the polycation lysine, it was obvious that another property of protamine contributed. This property was not linked to hyperosmolar, hypertensive or vasodilatory barrier opening, but may be a direct, cytotoxic effect of protamine. It is discussed whether barrier opening through transendothelial vesicular or channel transport occurs only at locations on the cell membrane deprived of negative surface charge areas.