Autophagy Is Activated in Injured Neurons and Inhibited by Methylprednisolone After Experimental Spinal Cord Injury

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Abstract

Study Design.

Experimental, controlled trial, animal study.

Objective.

To assess autophagy expression after rat spinal cord injury (SCI) and investigate the effect of methylprednisolone treatment on autophagy.

Summary of Background Data.

Although it is evident that SCI induces necrosis and apoptosis, its relationship to autophagy is uncertain. Autophagy is implicated in various pathological states in the nervous system, such as neurodegenerative diseases, cerebral ischemia, and traumatic brain injury. Up to now, no autophagy expression was evidenced by transmission electronic microscope (TEM) and the autophagy marker, microtubule-associated protein light chain 3 (LC3) in neural tissue after SCI.

Methods.

Sixty-six Sprague-Dawley rats were used for the experimental procedure. In the SCI group, laminectomy at T9 were performed, followed by impactor contusion of the spinal cord. In the sham group, only a laminectomy was performed without contusion. We used Western blot to analyze LC3 at 2 hours, 4 hours, 1 day, 3 days, and 7 days after SCI. We also investigated the effect of methylprednisolone on autophagy expression of contused spinal cord. Cellular localization and ultrastructural changes after spinal cord injury were compared with those sham-operated rats using immunofluorescent double labeling and TEM, respectively. Data from the Western blot were analyzed using a nonparametric Kruskal-Wallis test with P < 0.05 being considered significant.

Results.

We detected significantly elevated level of LC3 2 hours after SCI, and then the level declined until 1 week after SCI. Methylprednisolone decreased LC3 expression at 2 hours after SCI. LC3 positive cells were colocalized with neuronal nuclei, but not with glial fibrillary acidic protein. The existence of autophagy and progress of autophagic cell death after SCI were confirmed by TEM.

Conclusion.

Through observing the enhanced autophagy expression in neurons soon after contusion injury and the inhibitive effect of methylprednisolone treatment, this study demonstrates the characteristics of autophagy expression after SCI and suggests that autophagic cell death may play a role in neuronal death after spinal cord trauma.

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