Embryonic exposure to bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate increased the permeability of blood-brain barrier in transgenic zebrafish (Tg flk1: EGFP) (Image by IHB) 

The blood-brain barrier (BBB) composed of monolayer endothelial cells between the plasma and brain cells is crucial for maintaining the homeostasis of the central nervous system (CNS). The novel brominated flame retardants (NBFRs) are believed to cause damage to the CNS via crossing the BBB because of their high fat-solubility. Although NBFRs have been detected in brain, there is a lack of evidence for their penetrability through the BBB, making it hard to understand their direct effects on CNS.   

The research group led by Prof. ZHOU Bingsheng from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences found that bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) had poor penetrability through BBB, but could increase the permeability of BBB by affecting the tight junctions, which may result in disturbed homeostasis across BBB, thus causing adverse effects on the nervous system. The study was published in Journal of Hazardous Materials. 

The researchers first used an in vitro model of human immortalized endothelial cells, hCMEC/D3, to evaluate the penetrability of TBPH, and found that TBPH has a lower Papp during different periods, suggesting that it had poor penetrability through BBB. They then used transgenic zebrafish (Tg flk1: EGFP) as an in vivo model, and confirmed that TBPH could affect the BBB permeability probably via affecting the transcription of genes encoding tight junction proteins. 

Using wild type zebrafish embryos/larvae, the researchers assessed the potential neurotoxicity of TBPH. The results showed that embryonic exposure to TBPH did not remarkably change the hatching, survival and malformation rates, neurotransmitter contents, or locomotor activity, possibly owing to that TBPH can hardly cross the BBB to pose direct exposure to the CNS. 

They also found that the opsins genes transcription and visual responsive behavior were inhibited in wildtype zebrafish larvae, and the alteration of phototactic response may have adverse effects on predator avoidance response which could increase the environmental risk of fish. The underlying mechanism should be further explored.