Department of Anesthesiology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China; Department of Anesthesiology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
Brain Res Bull. 2022 Jun 1;183:116-126. doi: 10.1016/j.brainresbull.2022.02.022. Epub 2022 Mar 3.
Surgical brain injury (SBI) is unavoidable in neurosurgery, and could aggravate secondary brain injury. Post-brain injury, multiple inflammatory factors are released, resulting in neuroinflammation and cell apoptosis, with subsequent brain edema and nerve function injury. TREM2, an immune protein mainly expressed in microglia, is an important link for nerve cells to participate in the inflammatory response. TREM2 and nuclear factor кB (NF-кB) are indeed closely associated with the release of inflammatory cytokines following brain injury. This work aimed to determine the inflammatory function of TREM2 in SBI, and to investigate whether TREM2 regulates interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) release through the NF-кB p65 signaling pathway. We established a rat model of SBI, and performed Western blotting (WB), immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) for further analysis. Next, brain edema and neurological score analyses were performed. Finally, whether TREM2 regulating NF-кB p65 signaling affects blood-brain barrier (BBB) permeability and nerve cell apoptosis was examined. We found that post-SBI, TREM2 was upregulated, and inflammation and brain injury were aggravated. After TREM2 downregulation, NF-кB p65 production, inflammation and brain injury were enhanced, suggesting that TREM2 may play a protective role by inhibiting NF-кB p65 production after SBI. Overall, these findings suggest that TREM2 in SBI may have protective effects on postoperative nerve and BBB damage, possibly in part via the NF-κB p65 pathway.
手术性脑损伤（SBI）在神经外科中不可避免，并且可能加重继发性脑损伤。脑损伤后，多种炎症因子被释放，导致神经炎症和细胞凋亡，随后出现脑水肿和神经功能损伤。TREM2 是一种主要在小胶质细胞中表达的免疫蛋白，是神经细胞参与炎症反应的重要环节。TREM2 和核因子-кB（NF-кB）确实与脑损伤后炎症细胞因子的释放密切相关。本研究旨在确定 TREM2 在 SBI 中的炎症功能，并研究 TREM2 是否通过 NF-кB p65 信号通路调节白细胞介素-1β（IL-1β）、IL-6 和肿瘤坏死因子-α（TNF-α）的释放。我们建立了 SBI 大鼠模型，并进行了 Western blot（WB）、免疫荧光（IF）和酶联免疫吸附试验（ELISA）进一步分析。接下来，进行脑水肿和神经评分分析。最后，检查 TREM2 是否通过调节 NF-кB p65 信号影响血脑屏障（BBB）通透性和神经细胞凋亡。我们发现 SBI 后 TREM2 上调，炎症和脑损伤加重。TREM2 下调后，NF-кB p65 产生、炎症和脑损伤增强，表明 TREM2 可能通过抑制 SBI 后 NF-кB p65 的产生发挥保护作用。总之，这些发现表明，SBI 中的 TREM2 可能对术后神经和 BBB 损伤具有保护作用，可能部分通过 NF-κB p65 通路。
