EN
INTRODUCTION: Neurotoxicity of silver nanoparticles has been confirmed in a lot of in vitro and in vivo studies using different experimental models. However, the mechanisms of the toxic action have not been fully clarified. Since nanoparticles have the ability to enter the brain and significantly accumulate in this organ, it is important to investigate their neurotoxic mechanisms. AIM(S): We examined the effect of prolonged exposure on blood-brain barrier (BBB) ultrastructure and expression of tight junctions protein components as opposed to the ionic silver. METHOD(S): In the current study we exposed adult rats to a low dose (0.2 mg/kg b.w.) of small (10 nm) citrate-stabilized silver nanoparticles (AgNPs). RESULTS: The BBB is a highly specialized structure composed of a basement membrane and microvascular endothelial cells which interact with pericytes, perivascular artrocytes and neurons forming neurovascular unit. Administration of AgNPs over a two-week period resulted in changes in BBB ultrastructure and integrity. TEM analysis revealed accumulation of AgNPs inside endothelial cells of microvessels, mainly in lysosomes. Ultrastructural features of enhanced permeability of cerebral microvessels were observed such as enhanced activity of pinocytotic vesicular system and swollen perivascular astrocytic end-feets. This suggests uptake of fluid and its transfer to parenchyma which further results in perivascular edema. Additionally, we observed changes in the level of mRNA of the main tight junction proteins such as claudine, ocludine, and ZO1 as well as PDGF and its receptor PDGFbR which constitute the signaling pathway between endothelial cells and pericytes. All these characteristic protein components are responsible for the integrity of BBB. CONCLUSIONS: The results of the current study demonstrate that exposure of adult rats to AgNPs induces BBB dysfunction leading to the enhanced permeability of cerebral microvessels.