Vol 11: Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the bimodal stage after ischemia-reperfusion injury in rats.Reportar como inadecuado



 Vol 11: Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the bimodal stage after ischemia-reperfusion injury in rats.


Vol 11: Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the bimodal stage after ischemia-reperfusion injury in rats. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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This article is from Journal of Neuroinflammation, volume 11.AbstractBackground: Spinal cord ischemia-reperfusion I-R involves two-phase injury, including an initial acute ischemic insult and subsequent inflammatory reperfusion injury, resulting in blood-spinal cord barrier BSCB dysfunction involving the TLR4 pathway. However, the correlation between TLR4-MyD88-dependent and TLR4-TRIF-dependent pathways in BSCB dysfunction is not fully understood. The aim of this study is to characterize inflammatory responses in spinal cord I-R and the events that define its clinical progression with delayed neurological deficits, supporting a bimodal mechanism of injury. Methods: Rats were intrathecally pretreated with TAK-242, MyD88 inhibitory peptide, or Resveratrol at a 12 h interval for 3 days before undergoing 14-minute occlusion of aortic arch. Evan’s Blue EB extravasation and water content were detected at 6, 12, 18, 24, 36, 48, and 72 h after reperfusion. EB extravasation, water content, and NF-κB activation were increased with time after reperfusion, suggesting a bimodal distribution, as maximal increasing were detected at both 12 and 48 h after reperfusion. The changes were directly proportional to TLR4 levels determined by Western blot. Double-labeled immunohistochemical analysis was also used to detect the relationship between different cell types of BSCB with TLR4. Furthermore, NF-κB and IL-1β were analyzed at 12 and 48 h to identify the correlation between MyD88-dependent and TRIF-dependent pathways. Results: Rats without functional TLR4 and MyD88 attenuated BSCB leakage and inflammatory responses at 12 h, suggesting the ischemic event was largely mediated by MyD88-dependent pathway. Similar protective effects observed in rats with depleted TLR4, MyD88, and TRIF receptor at 48 h infer that the ongoing inflammation which occurred in late phase was mainly initiated by TRIF-dependent pathway and such inflammatory response could be further amplified by MyD88-dependent pathway. Additionally, microglia appeared to play a major role in early phase of inflammation after I-R injury, while in late responding phase both microglia and astrocytes were necessary. Conclusions: These findings indicate the relevance of TLR4-MyD88-dependent and TLR4-TRIF-dependent pathways in bimodal phases of inflammatory responses after I-R injury, corresponding with the clinical progression of injury and delayed onset of symptoms. The clinical usage of TLR4 signaling inhibitors at different phases may be a therapeutic option for the prevention of delayed injury.



Autor: Li, Xiao-Qian; Lv, Huang-Wei; Tan, Wen-Fei; Fang, Bo; Wang, He; Ma, Hong

Fuente: https://archive.org/







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