Wang Yi, Machizawa Maro G, Lisle Turner, Williams Cedric L, Clarke Ryon, Anzivino Matthew, Kron Irving, Lee Kevin S
Department of Neuroscience, University of Virginia, Charlottesville, VA, United States.
Department of Surgery, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA, United States.
Front Cell Neurosci. 2022 Feb 24;16:780880. doi: 10.3389/fncel.2022.780880. eCollection 2022.
Post-operative cognitive dysfunction (POCD) can be a serious surgical complication, and patients undergoing cardiac procedures are at particular risk for POCD. This study examined the effect of blocking neuroinflammation on behavioral and neurogenic deficits produced in a rat model of cardiopulmonary bypass (CPB). Minocycline, a drug with established anti-inflammatory activity, or saline was administered daily for 30 days post-CPB. Treatment with minocycline reduced the number of activated microglia/macrophages observed in the dentate gyrus of the hippocampus at 6 months post-CPB, consistent with an anti-inflammatory action in this CPB model. Behavioral testing was conducted at 6 months post-CPB utilizing a win-shift task on an 8-arm radial maze. Minocycline-treated animals performed significantly better than saline-treated animals on this task after CPB. In addition, the CPB-induced reduction in adult neurogenesis was attenuated in the minocycline-treated animals. Together, these findings indicate that suppressing neuroinflammation during the early post-surgical phase can limit long-term deficits in both behavioral and neurogenic outcomes after CPB.
术后认知功能障碍（POCD）可能是一种严重的手术并发症，接受心脏手术的患者发生POCD的风险尤其高。本研究考察了阻断神经炎症对体外循环（CPB）大鼠模型中产生的行为和神经发生缺陷的影响。在CPB后每天给予具有既定抗炎活性的药物米诺环素或生理盐水，持续30天。米诺环素治疗减少了CPB后6个月在海马齿状回中观察到的活化小胶质细胞/巨噬细胞数量，这与该CPB模型中的抗炎作用一致。在CPB后6个月使用八臂放射状迷宫上的赢-转换任务进行行为测试。CPB后，米诺环素治疗的动物在该任务上的表现明显优于生理盐水治疗的动物。此外，在米诺环素治疗的动物中，CPB诱导的成年神经发生减少得到了缓解。总之，这些发现表明，在术后早期抑制神经炎症可以限制CPB后行为和神经发生结果的长期缺陷。
