PMID- 35656867 OWN - NLM STAT- MEDLINE DCOM- 20220923 LR - 20221117 IS - 1554-6578 (Electronic) IS - 0022-3069 (Print) IS - 0022-3069 (Linking) VI - 81 IP - 10 DP - 2022 Sep 19 TI - Inhibiting Matrix Metalloproteinases Protects Evoked Electromyography Amplitudes and Muscle Tension in the Orbicularis Oris Muscle in a Rat Model of Facial Nerve Injury. PG - 816-824 LID - 10.1093/jnen/nlac041 [doi] AB - Facial nerve injury results in degradation of the neuromuscular junction (NMJ) and blocks neurotransmission between the pre- and postsynaptic structures, which are separated by a synaptic cleft. Matrix metalloproteinases (MMPs), enzymes that degrade and modify the extracellular matrix, play critical roles in regulating NMJ remodeling. We previously demonstrated that MMP1, MMP2, MMP3, MMP7, and MMP9 are overexpressed in facial nerve-innervated orbicularis oris muscle after facial nerve injury in a rat model. In the present study, the MMP inhibitor prinomastat was administered to rats after facial nerve injury. The MMP levels, agrin expression, and muscle-specific kinase (MuSK) phosphorylation were evaluated. Variations in evoked electromyography (EEMG) amplitude were also recorded. Compared with the control group, MMP expression in the orbicularis oris after facial nerve injury was significantly reduced in the prinomastat group. Inhibition of MMP expression maintained agrin expression and MuSK phosphorylation; the NMJ morphology was also protected after the injury. Moreover, prinomastat treatment sustained EEMG amplitude and muscle tension after the injury. These findings indicate that inhibiting MMPs can protect the function and morphology of the NMJ and demonstrate the need for protection of the NMJ at early stages after facial nerve injury. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. FAU - Wu, Shuang AU - Wu S AD - From the Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Song, Lijun AU - Song L AD - Hebei North University, Zhangjiakou, Hebei, P.R. China. FAU - Yu, Meirong AU - Yu M AD - From the Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Gong, Chao AU - Gong C AD - From the Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Chen, Lianhua AU - Chen L AD - From the Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (Agrin) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Organic Chemicals) RN - 10T6626FRK (prinomastat) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.23 (Matrix Metalloproteinase 7) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Agrin MH - Animals MH - Electromyography/methods MH - Facial Muscles/innervation/metabolism MH - *Facial Nerve Injuries/metabolism MH - Matrix Metalloproteinase 1 MH - Matrix Metalloproteinase 2 MH - Matrix Metalloproteinase 3 MH - Matrix Metalloproteinase 7 MH - Matrix Metalloproteinase 9 MH - Matrix Metalloproteinase Inhibitors MH - Muscle Tonus MH - Organic Chemicals MH - Rats PMC - PMC9487608 OTO - NOTNLM OT - Extracellular matrix metalloproteinases OT - Facial nerve injury OT - Neuromuscular junction OT - Orbicularis oris OT - Prinomastat EDAT- 2022/06/04 06:00 MHDA- 2022/09/24 06:00 PMCR- 2022/06/03 CRDT- 2022/06/03 05:43 PHST- 2022/06/04 06:00 [pubmed] PHST- 2022/09/24 06:00 [medline] PHST- 2022/06/03 05:43 [entrez] PHST- 2022/06/03 00:00 [pmc-release] AID - 6599859 [pii] AID - nlac041 [pii] AID - 10.1093/jnen/nlac041 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 2022 Sep 19;81(10):816-824. doi: 10.1093/jnen/nlac041.