The Effect of Acute Cadmium Exposure on the Vascular Endothelial Barrier Antigen and Astrocyte Morphology in the Developing Rat Central Nervous System

Abstract

Cadmium is a non‐biodegradable heavy metal and a major worldwide environmental pollutant. Clinical and experimental studies have documented the neurotoxic and behavioral effects of cadmium. However, the exact pathophysiologic mechanism(s) of the toxicity of cadmium for the human central nervous system is not completely understood. A literature review indicates that disruption of the blood‐brain barrier (BBB) structures is a key event in the pathogenesis of central nervous system disorders including cadmium neurotoxicity and infectious diseases. Several BBB‐associated proteins, including occludins, junctional adhesion molecules and claudins, among others, have been identified and used for evaluating BBB disruption under pathological conditions. A developmentally regulated rat blood‐brain barrier (BBB)‐specific capillary endothelial marker, the endothelial barrier antigen (EBA), has been previously isolated and classified by Sternberger and others. In previous studies, we have demonstrated that anti‐EBA exclusively recognizes barrier‐competent microvessels in the rat central and peripheral nervous system (CNS and PNS) and is negative in endothelial cells of peripheral tissues such as the heart and kidney. The antigen is also absent in brain microvessels possessing fenestrated endothelia such as the median eminence, organum vasculosum of lamina terminalis (ovalt) and pineal gland. In our current study, we applied a double, sequential indirect immunofluorescent protocol with anti‐EBA and an antibody directed against glial fibrillary acidic protein (GFAP), to examine the immunoreactivity patterns and morphological alterations in BBB microvessels and astrocytes, following acute exposure to a single, high dose of cadmium in young rats. We detected a moderate reduction in immunoreactivity and number of microvessels labelled by the anti‐EBA in the forebrain, cerebellum and midbrain in cadmium‐exposed rats compared to normal controls. Within the white and gray matter of cadmium‐exposed brains, we observed weakly GFAP‐reactive astrocytes displaying cell bodies with ill‐defined borders and blurry cytoplasm. The astrocyte nuclei appeared markedly enlarged, intensely hyperchromatic and exhibited marked chromatin condensation with varying degree of nuclear fragmentation. The weakly GFAP‐positive cell processes were hypertrophic and showed less branching compared to the strongly GFAP‐positive, highly branched astrocytes. Thus, indicating that EBA is involved in the pathogenesis of cadmium neurotoxicity in the rat model system.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.