Effect of MEK inhibitors on glial scar formation after acute spinal cord injury

English Keywords:Spinal cord injury  Inhibitors of mitogen-activated ERK-regulating kinase  Glial scar formation  Glial fibrillary acidic protein  Vimentin

English Abstract:

  【Abstract】 Objectives: To investigate the influence and mechanism of the MEK inhibitors on glial scar formation after acute spinal cord injury in a rat model. Methods: Thirty-six adult female Sprague-Dawley rats were divided randomly into sham injury group(group I), SCI group(group Ⅱ), and U0126 treatment group(group Ⅲ). SCI lesions in group II and III were made by modified Allen′s impact device; while the sham injury group only accepted the pseudo-operation. Locomotor capacity was assessed based on the 21-point Basso, Beattie and Bresnahan score at 1d, 3d, 5d, 7d, 14d, 21d and 28d after injury. Somatosensory evoked potentials were used to assess neurologic recovery. While the lesions were obtained and studied by conventional histology, GFAP and Vim immunohistochemistry(HIC) by using light microscopy at 14d and 28d after injury. The rats were sacrificed at 14 and 28 days after SCI, perfusion fixed. Results: There was no obvious changes in BBB score and other index in group Ⅰ. After SCI, hind limbs motor function in group Ⅱ and group Ⅲ showed varied degrees of recovery, after 28 days, the BBB score in group Ⅱ was 12.00±1.70, and it was 16.5±1.08 in group Ⅲ, group Ⅲ improved more remarkably than group Ⅱ(P<0.05). Somatosensory evoked potentials prolonged after SCI, while the amplitude decreased significantly; the latency and amplitude in group Ⅲ increased significantly than group Ⅱ(P<0.05), the incubation period in group Ⅲ at 28 days was 16.86±0.55ms, and the amplitude was 4.19±0.11μV. HE staining showed glial cells increased after SCI, glial scar formed obviously at 28 days. Compared with group Ⅱ, the scar volume in group Ⅲ was smaller; astrocytes activation and proliferation of GFAP expression significantly increased in group Ⅱ and group Ⅲ. At 14 days, the GFAP expression in two groups was 143.56±1.09 and 133.56±3.31 respectively; Vim expression of the two groups was 110.68±9.41 and 102.44±6.93 respectively. At 28 days, the GFAP and Vim of the two groups were 110.68±9.41, 102.44±6.93 and 72.96±4.16, 66.44±4.46 respectively. The expressions of GFAP and Vim significantly decreased after intervention of U0126(P<0.05). Conclusions: MEK inhibitors can inhibit star glial cell proliferation as well as the expression of GFAP and Vim, which can decrease glial scar formation, and then improve the hindlimb motor function.