Silver Nanoparticles Crossing Through and Distribution in the Blood-Brain Barrier In Vitro

Abstract

Silver nanoparticles (SNPs) translocate to the brain through the blood stream after they are implanted in vivo. The aim of this study was to investigate the distribution of SNPs that crossed through the blood-brain barrier (BBB). An in vitro BBB model established by co-cultures of rat brain microvessel vascular endothelial cells (BMVECs) with astrocytes (ACs) was cultured with cell culture medium containing 100 microg/mL of either SNPs or silver microparticles (SMPs). After 4 hours of culture, the ultrastructure and its silver content of BBB was evaluated with transmission electronic microscopy (TEM) and inductively-coupled plasma mass spectrometry (ICP-MS) respectively. Results demonstrated that SNPs crossed the BBB and accumulated inside BMVECs, while the SMPs did not. The data indicated a special distribution of SNPs in the BBB and suggested that SNPs pass the BBB mainly by transcytosis of capillary endothelial cells. Further study would be necessary to evaluate the actual biological effects of SNPs on the brain.

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…It was demonstrated using an in vitro BBB model that AgNPs can pass the BBB mainly by transcytosis and accumulate inside endothelial cells of microvessels [134]. Moreover, there is evidence that AgNPs induce the release of IL-1β and TNF-α in rat brain microvessels and that this leads to inflammation and a subsequent increase in the permeability of the BBB [137].…”

Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

“…24 Several studies have demonstrated that Ag-NPs can enter the CNS 25 and induce brain edema and neurotoxicity. 10,11,[26][27][28][29] Our previous studies showed that Ag-NPS and/or released Ag ions crossed the BBB and subsequently caused damage to astrocytes and neurons. 23 Cadherin and claudin expression were slightly changed in the Ag-NPS-exposure group, and astrocyte swelling was the most significant change after a 2-week gastrointestinal exposure to 1 mg/kg or 10 mg/kg of Ag-NPS in rats.…”

“…In recent years, how Ag-NPs induce BBB dysfunction and neurotoxicity has been of particular interest, because Ag-NPs have been shown to enter the brain by crossing the BBB in vitro and in vivo. [7][8][9][10] Previous studies reported that intravenous or subcutaneous injection of Ag-NPs can induce BBB dysfunction, astrocyte swelling, and neuronal degeneration in rats. [7][8][9] The BBB permeability mechanisms of Ag-NPs were further investigated using an in vitro BBB model (cocultures of rat brain microvascular endothelial cells with astrocytes).…”

“…The results showed that Ag-NPs crossed the BBB mainly by transcytosis rather than through the paracellular pathway. 10 Another study showed that Ag-NPs can increase BBB permeability and interact with the cerebral microvascular unit, producing a proinflammatory cascade that may further induce brain inflammation and neurotoxicity. 11 Most of the studies of Ag-NP-induced BBB dysfunction only focused on permeability changes and/or toxicity to the endothelial cells.…”

Silver nanoparticle exposure induces rat motor dysfunction through decrease in expression of calcium channel protein in cerebellum

“…Previous studies revealed that silver nanoparticles (AgNPs) were able to be translocated by blood circulation and distributed throughout the main organs in the form of particles (Tang et al, 2009). Given that AgNPs are capable of permeating the tight blood-brain barrier (BBB) and entering the brain tissue (Tang et al, 2010), the issue on assessing the specific responses of neurons to AgNPs is of great relevance. Animal studies proved that intravenous injection of AgNPs in Sprague-Dawley (SD) rats caused the functional injury of central nervous system (CNS) by decreasing their locomotor activity (Zhang et al, 2013), showing the potential neurotoxicity of AgNPs.…”