Brain edema and gliopathy induced by 6-aminonicotinamide intoxication in the central nervous system of rats.

Brain edema was produced by 6-aminonicotinamide (6-AN) in the rat with accompanying metabolic disturbance due to the accumulation of an antimetabolite of nicotinamide in the CNS. Twenty-four hours after intraperitoneal administration of 6-AN, significant (P less than 0.01) increases of sodium and water in the medulla oblongata were observed. By electron microscopy, the lesion was characterized by swelling of the perivascular neuroglial processes, producing disturbances of the active transport in the cell membrane and increased pinocytosis in the endothelial cells, especially of the arterioles and venules. The metabolic inhibitor was shown to produce not only an increased water and sodium uptake in neuroglias, which is characteristic of cytotoxic brain edema, but also produced protein-rich edema in the extracellular space, ie, vasogenic brain edema. The protein transport in the metabolic disturbance caused by 6-AN was traced, using horseradish peroxidase, revealing that it occurred from the vasculature into the extracellular spaces via pinocytotic vesicles due to the change in the cerebrovascular permeability.