Department of Anesthesiology, Ningbo NO. 2 Hospital, Ningbo 315010, China; Department of Pain, Ningbo NO. 2 Hospital, Ningbo 315010, China.
Department of Anesthesiology, Ningbo NO. 2 Hospital, Ningbo 315010, China.
Brain Res Bull. 2023 Nov;204:110799. doi: 10.1016/j.brainresbull.2023.110799. Epub 2023 Oct 29.
This study was designed to investigate the role of pericytes in the pathogenesis of perioperative neurocognitive disorder (PND).
In this study, we established a PND model via sevoflurane anesthesia and tibial fracture surgery in 2-month-old and 16-month-old male C57BL/6 mice. On the third postoperative day, the mice were subjected to behavioral testing or sacrificed to collect brain tissue. The progression of hippocampal blood-brain barrier (BBB) disruption and neuroinflammation was detected using transmission electron microscope and immunofluorescence. We also used western blotting to measure the levels of plasma-derived protein immunoglobulin G (IgG) and albumin in the hippocampus to assess the leakage of the BBB.
Aged mice did not experience age-related cognitive decline and BBB disruption compared with younger mice but only increased glial cell activity. Anesthesia/Surgery damaged cognitive function, reduced pericyte coverage, decreased the length of capillaries and levels of occludin and claudin-5, destroyed the structure of the BBB, exacerbated IgG and albumin accumulation in the hippocampus, and enhanced the activation of microglia and astrocytes in the hippocampus of aged mice. However, these negative effects did not occur in young mice.
Our study showed that the loss of pericytes led to increased BBB permeability and neuroinflammation after anesthesia/surgery in aged mice, ultimately resulting in cognitive dysfunction.
本研究旨在探讨周细胞在围手术期神经认知障碍（PND）发病机制中的作用。
在这项研究中，我们通过七氟醚麻醉和胫骨骨折手术建立了 2 月龄和 16 月龄雄性 C57BL/6 小鼠的 PND 模型。术后第 3 天，对小鼠进行行为测试或处死以收集脑组织。通过透射电镜和免疫荧光检测海马血脑屏障（BBB）破坏和神经炎症的进展。我们还使用 Western blot 测量海马中血浆衍生蛋白免疫球蛋白 G（IgG）和白蛋白的水平，以评估 BBB 的渗漏。
与年轻小鼠相比，老年小鼠没有经历与年龄相关的认知能力下降和 BBB 破坏，但仅增加了神经胶质细胞的活性。麻醉/手术损害了认知功能，减少了周细胞的覆盖，降低了毛细血管的长度和紧密连接蛋白 5（occludin 和 claudin-5）的水平，破坏了 BBB 的结构，加剧了老年小鼠海马中 IgG 和白蛋白的积累，并增强了海马中小胶质细胞和星形胶质细胞的激活。然而，这些负面影响并未出现在年轻小鼠中。
我们的研究表明，麻醉/手术后老年小鼠周细胞丢失导致 BBB 通透性增加和神经炎症，最终导致认知功能障碍。
