Overexpression of netrin-1 increases the expression of tight junction-associated proteins, claudin-5, occludin, and ZO-1, following traumatic brain injury in rats

The function of the blood-brain barrier (BBB) depends on the integrity of tight junction (TJ)-associated proteins. Netrin-1 is known to promote angiogenesis and may also regulate the BBB. To understand the association between netrin-1 and the TJ-associated proteins, the expression levels of proteins involved in maintaining the integrity of the BBB, including netrin-1, claudin-5, occludin and zonula occluden (ZO)-1, were investigated in the present study using quantitative polymerase chain reaction, western blot analysis and immunofluorescence. The aim of the present study was to determine the changes in BBB permeability and whether pZsGreen1-N1 mediated overexpression of netrin-1 increased the expression of the TJ-associated proteins following traumatic brain injury (TBI). The results demonstrated that the levels of mRNA transcription and protein expression of the TJ-associated proteins, claudin-5, occludin and ZO-1, were significantly reduced following TBI. Furthermore, the changes in the expression of these three TJ proteins were consistent with the changes in the BBB permeability, indicating that weakening intercellular junctions leads to BBB opening. The present study also demonstrated that netrin-1 significantly increased the downregulation of claudin-5, occludin and ZO-1 expression levels induced by TBI, which provided a basis for further investigation on the role of netrin-1 in the integrity of TJs and proper functioning of the BBB.