Involvement of the blood-brain barrier opening in cognitive decline in aged rats following orthopedic surgery and high concentration of sevoflurane inhalation.

Abstract

The underlying causes of postoperative cognitive decline (POCD) in old patients remained unelucidated, and there are little descriptions on mechanisms associated with the blood-brain barrier (BBB) disruption during POCD. We therefore tested the effects of orthopedic surgery with different concentrations of sevoflurane for 2 h on the behavior test and the BBB permeability in aged rats. 18-month rats were divided into control group and surgical group with propofol anesthesia (0.7 mgkg(-1) min(-1)) and 1.0 MAC, 1.3 MAC, and 1.5 MAC sevoflurane inhalation for 2 h. We assessed their cognitive function via Y-maze and fear conditioning test on day 1, 3, and 7 after experiments. Animals were then assigned to control group, propofol (2 h, 0.7 mgkg(-1) min(-1)) group, surgery plus propofol group and surgery plus 1.5 MAC sevoflurane inhalation for 2h. Their hippocampal BBB permeability was detected with Evans blue quantification. Alterations of tight junctions in hippocampus were measured with occludin and claudin-5 western blot. Then we assessed matrix metalloproteinase-2,9 (MMP-2,9) via western blot and immunohistochemistry staining at day 1, 3, 7, and 14 after experiments. Surgery impaired cognitive function and increased Evans blue leakage into the hippocampus in aged rats while 2 h of 1.5 MAC sevoflurane inhalation potentiated these effects. Surgery induced occludin protein expression decreases and MMP-2,9 proteins increase and these influences can be enhanced by high concentration of sevoflurane inhalation. In conclusion, 1.5 MAC sevoflurane for 2 h exacerbated cognitive impairment induced by orthopedic surgery in aged rats and the breach in BBB may be involved in this process.