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Am J Transl Res. 2017 Sep 15;9(9):4261-4270. eCollection 2017.

Autophagy plays a protective role in motor neuron degeneration following spinal cord ischemia/reperfusion-induced spastic paralysis.

Author information

1
State Key Laboratory of Trauma, Burns and Combined Injury, 3rd Department of Research Institute of Surgery, Daping Hospital, Third Military Medical UniversityChongqing 400042, P. R. China.
2
Department of Orthopaedics, The Second Affiliated Hospital of Luohe Medical College462300, Henan, P. R. China.

Abstract

Spinal cord ischemia and reperfusion (SCIR) injury can lead to neurologic dysfunction and paraplegia, which are serious complications after shock or thoracoabdominal aortic surgery. Autophagy is a fundamental cellular process in eukaryotes, and homeostasis of autophagic activities in the cytoplasm is critical for the maintenance of neuronal function. To date, no studies have addressed the involvement of autophagy in the regulation of motor neurons in the ventral horn of the spinal cord area following SCIR-induced spastic paralysis or the underlying mechanisms of this process. In this study, we investigated spastic paralysis in rats following SCIR injury. The number of autophagosomes increased 3 h following the injury, and subsequently decreased slowly to near-normal levels in the sham group as indicated by the autophagy markers microtubule-associated protein 1 light chain 3 (LC3), beclin-1, and p62. Furthermore, after treatment with the autophagy inhibitor 3-Methyladenine (3-MA) and autophagy activator rapamycin following SCIR, autophagy in the SCIR-3-MA group decreased significantly, while that in the SCIR-Rap group increased, compared with SCIR-DMSO controls group. Moreover, the assessment of motor neurons function, using Reuter's score and motor evoked potentials (MEP) and somatosensory evoked potentials (SEP), indicated that promoting autophagy reduced scores compared with SCIR controls, while inhibiting autophagy increased the scores, and hence motor neurons function. Autophagy in the SCIR model protected motor neurons function and morphology. These results would provide more evidences for better understanding function of autophagy in motor neurons degeneration and mechanisms underlying spastic paralysis. Autophagy would be a novel target for prevention and therapy in SCIR damage.

KEYWORDS:

Spinal cord ischemia reperfusion injury; autophagy; motor neurons; rapamycin and 3-MA; spastic paralysis

PMID:
28979699
PMCID:
PMC5622268

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