Protective effect of rhEPO on tight junctions of cerebral microvascular endothelial cells early following traumatic brain injury in rats

• Published in: Brain injury Vol. 30; no. 4; p. 462
• Main Authors: Zhiyuan, Qian, Qingyong, Li, Shengming, Huang, Hui, Ma
• Format: Journal Article
• Language: English
• Published: England 20.03.2016
• Subjects: Animals; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiopathology; Brain Injuries, Traumatic - pathology; Brain Injuries, Traumatic - prevention & control; Claudin-5 - genetics; Claudin-5 - metabolism; Disease Models, Animal; Drug Administration Schedule; Endothelial Cells - pathology; Erythropoietin - therapeutic use; Gene Expression Regulation - drug effects; Occludin - genetics; Occludin - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tight Junctions - drug effects; Time Factors; Zonula Occludens-1 Protein - genetics; Zonula Occludens-1 Protein - metabolism; cerebral endothelial cell; rhEPO; Traumatic brain injury; blood–brain barrier; tight junction
• ISSN: 1362-301X
• DOI: 10.3109/02699052.2015.1080386

The goal of this study was to investigate the protective effect of recombinant human EPO(rhEPO) on cerebral microvascular endothelial cells and the mechanisms by which rhEPO interacts with TJs proteins, claudin-5, Occludin and ZO-1 during the early period following traumatic brain injury. Rats (n = 81) were randomly divided into sham-operated group, TBI group and rhEPO+TBI group. Traumatic brain injury was induced by the Marmarou method. Rats were killed at 3, 24, 72 and 168 hours after TBI. The integrity of the blood-brain barrier was investigated by using a spectrophotometer to assess extravasation of Evans blue dye. The expression of Claudin-5, Occludin and ZO-1 were determined by immunohistochemistry and real-time fluorescence quantitative PCR. From 3 hours to 3 days, rats in the TBI group demonstrated a remarkable increase in Evans blue content in the brain, relative to rats in the sham-operated group (p < 0.05). The expression of Claudin-5 and Occludin was significantly lower than those in the sham-operated group (p < 0.05). In contrast, rats in the TBI+rhEPO group demonstrated a significant decrease in brain levels. It was found that administration of rhEPO protected cerebral microvascular endothelial cells and reduced permeability of BBB and the mechanisms may be due to increasing the expression of TJs proteins.