Blood-brain barrier damage by 2-methyl-4-chlorophenoxyacetic acid herbicide in rats

The integrity of blood-brain barrier (BBB) to serum proteins was studied in rats acutely intoxicated by 2-methyl-4-chlorophenoxyacetic acid (MCPA). Intoxication was produced by giving sodium salt of MCPA sc in single doses of 100, 250, and 500 mg/kg at various intervals before killing the animals. Evans blue, immunohistochemistry of serum proteins, and electron microscopy were used to study the barrier. Extravasations of Evans blue-albumin complex indicating BBB damage were observed with the 250 and 500 mg/kg doses. Lateral cerebral cortex and medulla oblongata were the tissues most consistently affected. Most severe extravasations occurred 4.5 hr after administration of 250 mg/kg MCPA. At 24.5 hr, no extravasation of Evans blue could be demonstrated, which suggests reversibility of the damage. The immunohistochemical demonstration of endogenous albumin or immunoglobulin-G verified the same localizations of the BBB damage. Electron microscopy of the damaged brain areas revealed increased amounts of vesicles in the endothelial cells and local swellings of the basal laminae of the capillaries. As indicated by the extent of extravasation of serum components into the brain, BBB damages appeared within 1.5 hr and showed a marked recovery in 24.5 hr. The damages coincided with the toxic symptoms of the herbicide. Thus the central nervous system was affected by MCPA intoxication.