CCL2 Inhibitor Bindarit Improve Postoperative Cognitive Function by Attenuating Pericyte Loss‐Related Blood–Brain Barrier Disruption and Neuroinflammation

作者：Hui Yuan, Bo Lu, Daofan Sun, Junping Chen, Xiangming Fang · 发表于：Mediators of Inflammation · 年份：2025 · DOI：10.1155/mi/7248780 · 被引用次数：2 · 研究领域：Barrier Structure and Function Studies、Neuroinflammation and Neurodegeneration Mechanisms、Cancer, Stress, Anesthesia, and Immune Response

Perioperative neurocognitive disorder (PND) is a common complication in elderly patients undergoing surgery and anesthesia and associated with the impaired recovery. Previous studies have demonstrated that PND was correlated with the pericyte (PC) loss in brain, but the underlying mechanisms remain unclear. This study investigates whether C-C motif chemokine ligand 2 (CCL2) in hippocampal tissues contributes to postoperative PC injury, blood-brain barrier (BBB) disruption, neuroinflammation, and cognitive dysfunction. Sixteen-month-old C57BL/6 mice underwent tibial fracture surgery to induce PND. CCL2 expression in hippocampal tissues was downregulated using intraperitoneal injections of 200 mg/kg daily Bindarit for 4 days prior to surgery. Behavioral tests were conducted on the third day postsurgery and brain tissues were collected. Western blotting assessed CCL2 expression in the hippocampus, immunofluorescence evaluated PC coverage, BBB integrity, and neuroinflammation, and transmission electron microscopy (TEM) examined BBB microstructure. Bindarit effectively inhibited the surgery-induced increase in hippocampal CCL2 expression and improved postoperative cognitive function. Behavioral tests, including the open field (OF) test and novel object recognition (NOR) test, indicated enhanced locomotor activity and short-term memory in Bindarit-treated mice compared to controls. Immunofluorescence analysis revealed that Bindarit treatment mitigated the reduction in capillary len...