Action mechanism of corticosteroids to aggravate Guillain-Barré syndrome

Abstract

Corticosteroids have been proved to be ineffective for Guillain-Barré syndrome, but the mechanism remains unknown. In a rabbit model of axonal Guillain-Barré syndrome, treatment with corticosteroids significantly reduced macrophage infiltration in the spinal ventral roots and the survival rate as well as clinical improvement. On 30(th) day after onset, there was significantly higher frequency of axonal degeneration in the corticosteroids-treated rabbits than saline-treated rabbits. Corticosteroids may reduce the scavengers that play a crucial role for nerve regeneration, thus delay the recovery of this disease.

Figure 1

(A) Staining of macrophage infiltration in the spinal ventral roots of acute motor axonal neuropathy (AMAN) rabbits one week after disease onset in methylprednisolone and saline groups. Scale bars indicate 200  μm. There was significant reduction of macrophage infiltration in methylprednisolone group than saline group. The numbers 1–6 represent the serial number of AMAN rabbits in different groups. The results were shown as mean ± standard error. (B) Voltage-gated sodium (Nav) channels cluster disruption and C3 deposition at the nodes of Ranvier in spinal ventral roots of AMAN rabbits. Representative immunofluorescence images of longitudinal sections of spinal ventral roots from the rabbits (50  μm). The activated C3 fragments were stained in green, Nav channels in red. As shown, the nodal Nav channel cluster is markedly disrupted together with the activated C3 fragment deposition in both methylprednisolone group and saline group. There was no difference in frequency of both Nav channel cluster disruption and activated C3 fragment deposition between methylprednisolone and saline groups. The numbers 1–6 represent the serial number of AMAN rabbits in different groups. The results were shown as mean ± standard error.

Figure 2

(A) Survival curves of rabbits up till 30 days after disease onset were shown. Five out of twelve rabbits died by day 30 after disease onset in methylprednisolone group. There was significant difference between the survival curves of methylprednisolone and saline groups (p = 0.04). (B) Changes in the clinical score (mean ± standard error) during the 30 days after disease onset. *p = 0.01.

Figure 3. Histological changes in the ventral roots of AMAN rabbits and the normal control were shown.

Scale bars indicate 50 μm. The frequency of axonal degeneration was significantly higher in methylprednisolone group (n = 7) than the saline group (n = 9) on the 30^th day after the initiation of treatment (p < 0.001). The results were shown as mean ± standard error.