Changes in the integrity of the blood-brain barrier in suckling rats with low dose lead encephalopathy

Summary Previous studies on the toxic effects of lead on the brains of young animals have shown damage to the blood-brain barrier (BBB) which in severe forms appears as hemorrhagic encephalopathy. In those studies the doses of lead have been of such magnitude that lead-induced anorexia resulting in growth retardation has contributed to the extent of the injury (Sundström et al. 1984). The growth retardation can be prevented by using low lead doses (Sundström et al. 1983). Consequently, we have examined to which extent the BBB is injured in suckling rats with low dose lead encephalopathy. This was done by a) testing the permeability of the BBB to plasma proteins and b) assessing the possible occurrence of vasogenic edema by measuring the specific gravity of brain tissue. Low dose lead encephalopathy was induced by daily i.p. injections of lead nitrate 10 mg/kg body weight (b.wt.) for the first 15 days. The lead contents of the blood and homogenates of the cerebrum and cerebellum were assayed by atomic absorption spectrophotometry.The brains were examined at 15, 20, or 30 days of age. When Evans blue-albumin (EBA) was injected i.v. 2 h before killing, most 15-day-old rats exposed to lead displayed a bluish discoloration in their cerebellum. Microscopically, red fluorescence of EBA was seen in the blue-stained regions. Immunohistochemically, extravasation of albumin, fibrinogen, and fibronectin was demonstrated as positive staining in the cerebellar cortex, with diffuse spread to the white matter of the corresponding folium. Neither lead-exposed rats aged 20 or 30 days nor any non-exposed rats revealed macroscopic or microscopic leakage of plasma proteins in the brain parenchyma. The specific gravity of the cerebral and cerebellar cortices and the hippocampus of control and lead-exposed rats aged 15 and 20 days was determined using density gradients of Percoll. No increment in the water content was encountered. Rather, the specific gravity of cerebellum of lead-treated rats aged 15 days was slightly higher than that of the controls, though statistical significance for this difference was reached only when nonparametric tests were applied. Our results indicate that low dose lead encephalopathy results in a breakdown of the BBB to plasma proteins without marked vasogenic brain edema. The hypothesis is advanced that the leakage of plasma results in rapid normalization of the tissue water content, whereas proteins remain longer in the parenchyma.Financed by grants from the Swedish Medical Research Council (project nos. 03488 and 07123), from the Medical Faculty, University of Göteborg, and from the Göteborg Royal Society for Sciences and Arts