The role and mechanism of Toll-like receptor 4 in traumatic brain injury

Abstract

Objective To study the role and mechanism of Toll-like receptor 4 (TLR4) in traumatic brain injury. Methods After 24 h brain injury, comparative study TLR 4 knockout [TLR4(-/-)]/wild type mice [TLR4(+ /+ )]. Edema area change of different groups is compared by magnetic resonance imaging (MRI) scan. Use real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) method to compare cytokines like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, and brain derived neurotrophic factor (BDNF) change between different groups. To compare important downstream signaling molecules Myeloid differentiation factor (MyD)88/nuclear factor-κB (NF-κB) changes in different groups, we use Western blotting. Results After 24 h of brain injury, significant difference were observed in different groups in Morris water maze test. TLR4(-/-) mice group showed shorter incubation period [(39.26±18.1) s] than TLR4(+ /+ ) mice [(50.19±16.5) s; t=2.361, P=0.021], and TLR4(-/-) mice group (2.04±1.18) showed more times across the platform than TLR4(+ /+ ) mice (0.60±0.47; t=3.000, P=0.011). Comparing to the edema area of TLR4(+ /+ ) mice group [(23.20±5.70)%], the area of TLR4 mice [(10.31±2.01)%] was smaller (t=5.643, P=0.000). Comparing to the TLR4(+ /+ ) mice, the expression of IL-10 [TLR4(-/-): 3.00±0.74; TLR4(+ /+ ): 1.20±0.27; t=6.046, P=0.000] and BDNF [TLR4(-/-): 55.67±7.94; TLR4(+ /+ ): 42.52±3.25; t=4.055, P=0.002] increased dramatically in TLR4(-/-) mice, while TNF-α[TLR4(-/-): 6.49±0.36; TLR4(+ /+ ): 8.89±0.57; t=9.419, P=0.000], IL-1β [TLR4 (-/-): 7.49±0.79; TLR4(+ /+ ): 12.76±1.06; t=10.547, P=0.000] decreased significantly. About the important downstream signaling molecules of TLR4, we found that activation of MyD88 (t=7.968, P=0.000)/NF-κB (t=6.198, P=0.000) in TLR4(-/-) mice is significant lower than that in TLR4(+ /+ ) mice. Conclusion After traumatic brain injury, the activation of TLR4 can promote the inflammatory response, resulting in more severe cerebral trauma, aggravating cerebral edema and secondary injury. In addition, MyD88/NF-κB signaling pathway plays an important role in this pathophysiological process. Key words: Traumatic brain injury; Toll-like receptor 4; Microglia polarization; Inflammatory response