Objective: In this study, chronic compression of cervical spinal cord was introduced into twy/twy mice and the role of MK2 signaling pathway was investigated in this disease.
Methods: twy/twy mice aged 6-24 weeks were used and the inflammatory response in the cervical spinal cord was observed. The Institute of Cancer Research (ICR) mice were used as controls. MK2 inhibitor (PF-3644022, 30 mg/kg) was administered intragastrically to twy/twy mice. The motor behavior was firstly observed in these three groups by Catwalk gait analysis. And the cervical spinal cord between C2 and C3 of vertebral segments was analyzed by MRI and Western blot assay.
Results: The stride length of paws and interlimb coordination reduced in twy/twy mice. However, at 4 weeks after PF-3644022 treatment, a marked improvement was observed in the motor function. The expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2 and p-MK2) and apoptosis related proteins (such as cleaved caspase-8 and bax/bcl-2) in the spinal cord of twy/twy mice significantly increased as compared to controls, but 4-week treatment with PF-3644022 markedly reduced the expressions of these factors and apoptotic proteins in the cervical spinal cord.
Conclusion: MK2 signaling pathway is involved in the chronic compression induced inflammation of the cervical spinal cord. Thus, to inhibit the MK2 pathway may used to improve the outcome and prevent the deterioration of neurological dysfunction.
Keywords: Cervical spinal cord; chronic compression; inflammation; mitogen-activated protein kinase-activated protein kinase 2.