An ultrastructural study on the blood-brain barrier dysfunction following mercury intoxication.

Abstract

Methyl mercuric chloride (CH3HgCl) was administered in a single intraperitoneal injection to adult male rats at a dosage of 10 mg/kg body weight. Horseradish peroxidase was systemically injected into these animals at various time intervals following methyl mercury administration. Horseradish peroxidase activity as demonstrated by 3,3′-diaminobenzidene conjugation was used as a tracer to study blood-brain barrier dysfunction induced by methyl mercury. Permeation of tracer into the parenchyma of the central nervous system was observed ultrastructurally as early as 4–6 hrs following methyl mercury administration. Examination of capillary regions in the calcarine cortex and cerebellum at this time also revealed many endothelial cells with mitochondrial injury, increased pinocytotic transport of tracer, and in several instances, widening of lateral leaflet spaces without disruption of tight junctions. 6 hrs after the intoxication, many astrocytic end-feet abutting these injured capillaries displayed swelling and tracer accumulation. Horseradish peroxidase activity could be localized within neuronal and glial elements after 10–12 hrs of methyl mercury treatment. A newly developed electron microscopic histochemical technique utilizing an ammonium sulfide reaction was also employed to study the distribution of mercury within the blood-brain barrier structures. Localization of mercury corresponded with observed sites of cellular injury and tracer extravasation. It is believed that the observed blood-brain barrier dysfunction was due to the impairment of endothelial cells and astrocytic end-feet by mercury ions.