PMID- 37506317 OWN - NLM STAT- MEDLINE DCOM- 20230811 LR - 20230816 IS - 1473-558X (Electronic) IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 34 IP - 13 DP - 2023 Sep 6 TI - TLR4-MyD88 signaling is involved in the spinal neurons during the full length of recovery from transection of the motor branch of the femoral nerve in mice. PG - 655-663 LID - 10.1097/WNR.0000000000001939 [doi] AB - This study was designed to see the expression of toll-like receptor 4 (TLR4) and downstream molecules including myeloid differentiation factor 88 (MyD88) and interleukin 1-beta (IL-1beta) in the spinal cord as peripheral nerve injury recovered in mice. We established a model of femoral nerve injury (FNI) in C57BL/6 mice by transection of the motor branch of the femoral nerve, followed by retrograde labeling to show the according motor neurons in the anterior horn of the spinal cord pars lumbar. We observed the motor function recovery of the injured hind limbs using behavioral tests. The expression of TLR4, MyD88, and IL-1beta was examined by immunofluorescent staining and western blot. According to the behavior test, the FNI animals fully recovered within 6-8 weeks. TLR4, MyD88, and IL-1beta were expressed in the ventral horn of the spinal cord both at 72 h till 6 weeks after the femoral nerve transection surgery, and these proteins were mostly co-localized with neurons. IL-1beta also tended to rise in the same surgery groups, but more intimate with microglia surrounding nearby retrograde labeled neurons. And western blot results were consistent with histological findings. The results indicate that peripheral nerve injury may induce innate immune reactions of the central neurons and critical signaling like TLR4/MyD88 in the spinal cord may reflect the recovery of the injury. These findings suggest that peripheral nerve injury triggered the TLR4/MyD88 signal in the soma of spinal neurons may be involved in function and nerve restoration through neuron-glia crosstalk. CI - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Wei, Xiaoyan AU - Wei X AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. AD - School of Medicine, Northwest University, Xi'an. FAU - Ding, Yumeng AU - Ding Y AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - Wang, Lichao AU - Wang L AD - Naval Medical Center, Naval Medical University, Shanghai, China. FAU - Zhang, Qixingmao AU - Zhang Q AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - Wang, Chunhuai AU - Wang C AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - Chen, Chen AU - Chen C AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - You, Siwei AU - You S AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - Wu, Mingmei AU - Wu M AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. FAU - Kuang, Fang AU - Kuang F AD - Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230717 PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Mice MH - Animals MH - *Myeloid Differentiation Factor 88/metabolism MH - *Peripheral Nerve Injuries MH - Toll-Like Receptor 4/metabolism MH - Femoral Nerve/metabolism MH - Mice, Inbred C57BL MH - Motor Neurons/metabolism PMC - PMC10399940 COIS- There are no conflicts of interest. EDAT- 2023/07/28 19:11 MHDA- 2023/08/11 06:43 PMCR- 2023/08/03 CRDT- 2023/07/28 15:43 PHST- 2023/08/11 06:43 [medline] PHST- 2023/07/28 19:11 [pubmed] PHST- 2023/07/28 15:43 [entrez] PHST- 2023/08/03 00:00 [pmc-release] AID - 00001756-990000000-00141 [pii] AID - 10.1097/WNR.0000000000001939 [doi] PST - ppublish SO - Neuroreport. 2023 Sep 6;34(13):655-663. doi: 10.1097/WNR.0000000000001939. Epub 2023 Jul 17.