Wu Muyao, He Xiaoyi, Gong Yating, Wang Chaoyu, Huang Yaqian, Gao Fan, Dang Baoqi
Department of Rehabilitation, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China.
Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China.
J Cent Nerv Syst Dis. 2024 Nov 20;16:11795735241301568. doi: 10.1177/11795735241301568. eCollection 2024.
Traumatic brain injury (TBI) can cause damage to the blood-brain barrier, resulting in neuroinflammatory reactions and brain edema that seriously affect the recovery of neurological function. We hypothesize that an enriched environment (EE) regulates the TLR2/NF-κB signaling pathway and thereby modulates the integrity of the blood-brain barrier to achieve neuroprotective effects.
This study evaluated the expression of toll-like receptor (TLR)-2 after TBI in a rat model, with the aim of determining whether TLR2/NF-κB improves secondary brain injury by inhibiting the release of inflammatory factors and reducing brain edema.
We established a TBI model using Sprague-Dawley rats and implemented EE intervention or TLR2 siRNA to reduce TLR2. Western-blot analysis, real-time PCR, immunofluorescence staining, ELISA, TUNEL and FJC staining, wet-dry methods, rotarod testing, and neurological scoring were then applied for analysis.
Our results revealed that TLR2 was activated after TBI in rats and that EE or silencing of TLR2 with TLR2 siRNA reduced the level of inflammation, significantly alleviating brain edema, neuronal apoptosis, and degeneration. TBI exacerbated brain edema and nerve damage caused by TLR2/NF-κB signaling, and EE appeared to regulate neuroinflammation and brain edema by reducing TLR2.
Inhibition of TLR2 with EE might constitute a successful approach in the management of TBI.
创伤性脑损伤（TBI）可导致血脑屏障受损，引发神经炎症反应和脑水肿，严重影响神经功能的恢复。我们推测，丰富环境（EE）可调节Toll样受体2（TLR2）/核因子κB（NF-κB）信号通路，从而调节血脑屏障的完整性，实现神经保护作用。
本研究评估了大鼠TBI模型中Toll样受体（TLR）-2的表达，旨在确定TLR2/NF-κB是否通过抑制炎性因子释放和减轻脑水肿来改善继发性脑损伤。
我们使用Sprague-Dawley大鼠建立TBI模型，并实施EE干预或使用TLR2小干扰RNA（siRNA）降低TLR2水平。随后采用蛋白质免疫印迹分析、实时荧光定量聚合酶链反应（PCR）、免疫荧光染色、酶联免疫吸附测定（ELISA）、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）和荧光金（FJC）染色、干湿重法、转棒试验和神经功能评分进行分析。
我们的结果显示，大鼠TBI后TLR2被激活，EE或用TLR2 siRNA沉默TLR2可降低炎症水平，显著减轻脑水肿、神经元凋亡和变性。TBI加剧了TLR2/NF-κB信号通路引起的脑水肿和神经损伤，而EE似乎通过降低TLR2来调节神经炎症和脑水肿。
EE抑制TLR2可能是治疗TBI的一种成功方法。
