Abstract
BackgroundPerioperative neurocognitive disorders (PND) occur frequently after surgery, especially in aged patients. Surgery-induced neuroinflammation and blood-brain barrier (BBB) dysfunction play a crucial role in the pathogenesis of PND. Interleukin-17A (IL-17A) increases after surgical stress and will be involved in BBB dysfunction. However, the effect of IL-17A on BBB function during PND remains poorly understood.MethodsMale wild-type C57BL/6J mice (15 months old) received tibial fracture surgery and fixation to establish the PND model. All the mice were injected intraperitoneally with an IL-17A-neutralizing antibody (Abs) or isotype-control Abs 30 min before tibial fracture surgery. Animal behaviour tests conducted 24 h after surgery included the contextual fear conditioning and Y maze tests. Serum and hippocampus IL-17A levels and hippocampus IL-6 and IL-1β levels were detected by ELISA. BBB function was detected by Evans blue (EB) test. Hippocampus matrix metalloproteinase-2 (MMP-2)- and MMP-9-positive cells were detected by immunohistochemistry. Hippocampus albumin, occludin, claudin-5 and IL-17A receptors were detected by Western blot. For the in vitro experiment, bEnd.3 cells were incubated with IL-17A. Cell IL-17A receptors were detected by immunofluorescence. Cellular MMP-2, MMP-9, occludin, and claudin-5 were detected by Western blot.ResultsTibial fracture surgery promoted memory impairment, increased levels of IL-17A and IL-17A receptors, inflammatory factor production and BBB dysfunction. IL-17A Abs inhibited this effect, including improving memory function, decreasing inflammatory factor production and alleviating BBB disruption, indicated by decreased tight junctions (TJs) and increased MMPs after surgery. The in vitro study suggested that recombinant IL-17A could upregulate the expression of IL-17A receptors, decrease TJs and increase the level of MMPs in bEnd.3 cells.ConclusionsOur results suggested that IL-17A-promoted BBB disruption might play an important role in the pathogenesis of PND.
Highlights
Perioperative neurocognitive disorders (PND) occur frequently after surgery, especially in aged patients
These results suggested that tibial fracture surgery-induced cognitive impairment could be alleviated by treatment with anti-IL-17A Neutralizing antibody (Abs)
Our study indicated that pretreatment with anti-IL-17A Abs could inhibit cognitive deficits following surgery, indicating that IL-17A was involved in surgery-induced cognitive decline.Neuroinflammation plays an important role in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and depression [37,38,39], and is believed to be a vital pathological mechanism of postoperative cognitive dysfunction [40]
Summary
Perioperative neurocognitive disorders (PND) occur frequently after surgery, especially in aged patients. Perioperative neurocognitive disorder (PND) is a recently recommended overarching term for cognitive impairment in the preoperative or postoperative period and is associated with increased mortality [1]. It is characterized as a decline in cognitive functions including memory, attention, information processing and cognitive flexibility [2]. BBB disruption allows the entry of neurotoxic debris, cells and pathogens and contributes to inflammatory and immune responses in the CNS [10]. Recent findings have suggested that BBB disruption is prevalent in the first 24 h after surgery, and dysfunction of the BBB may facilitate the passage of peripheral immune cells and mediators to the brain, which promotes brain inflammation and neuronal damage [16, 17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
