Neuroprotective effect of minocycline on expression of glial cell line-derived neurotrophic factor in facial motoneurons of rats after facial nerve ischemia

Abstract

Objective To explore the neuroprotective mechanism of minocycline in facial motoneurons by studying the neuroprotective effect of minocycline on expression of glial cell-derived neurotrophic factor (GDNF) in rats after facial nerve ischemia. Methods One hundred and twenty male Sprague-Dawley rats were randomly divided into sham-operated (SH) group, petrosal artery interruption (PAI) group and minocyline treated (MC) group (n=40). Facial nerve ischemia models in the later two groups were established by occluding the tympanic segment of the petrosal artery. The rats in MC group were given intragastric injection of minocycline (60 mg/kg) each day, while rats in the PAI and SH groups were given the same amount of normal saline. The animals were executed 3, 7, 14, 28 days after ischemia. The histopathological changes of facial neurons were observed by hematoxylin and eosin (HE) staining. The apoptosis changes in facial motoneurons were detected by Terminal deoxynucleoside transferase mediated-dUTP nick end labeling (TUNEL). The protein expression of GDNF was measured by immunohistochemistry staining and Western blotting. Results HE staining results showed that MC group had less severe nerve damage (shrank neuronal somas, condensation of cytoplasm and unconspicuous axon) than PAI group. The TUNEL results showed that the number of apoptotic cells in MC group was significantly fewer than that in PAI group at each time point (P<0.05). Immunohistochemistry and Western blotting indicated increased GDNF protein expression in the PAI group and MC group as compared with that in the SH group, and the GDNF expression in MC group was significantly higher than that in PAI group (P<0.05). Conclusion Minocycline could play a strong neuroprotective effect on facial motoneurons of rats after facial nerve ischemia by enhancing GDNF expression and inhibiting facial motoneurons apoptosis. Key words: Minocycline; Facial nerve; Ischemia injury; Apoptosis; Glial cell line-derived neurotrophic factor