4.3 Article

Inhibiting Matrix Metalloproteinases Protects Evoked Electromyography Amplitudes and Muscle Tension in the Orbicularis Oris Muscle in a Rat Model of Facial Nerve Injury

Journal

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlac041

Keywords

Extracellular matrix metalloproteinases; Facial nerve injury; Neuromuscular junction; Orbicularis oris; Prinomastat

Funding

  1. National Natural Science Foundation of China [81870714]

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Facial nerve injury leads to degradation of the neuromuscular junction and inhibits neurotransmission. Matrix metalloproteinases play critical roles in regulating NMJ remodeling. Treatment with the MMP inhibitor prinomastat after facial nerve injury can protect the function and morphology of the NMJ.
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.

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