Abstract
Spinal cord ischemia is a severe clinical complication induced by thoracoabdominal aortic surgery, severe trauma, or compression to the spinal column. As one of the most important functional cells in the spinal cord, spinal motor neurons (SMNs) suffer most during the process since they are vulnerable to ischemic injury due to high demands of energy. Previous researches have tried various animal models or organotypic tissue experiments to mimic the process and get to know the pathogenesis and mechanism. However, little work has been performed on the cellular model of spinal cord ischemia, which has been hampered by the inability to obtain a sufficient number of pure primary SMNs for in vitro study. By optimizing the isolation and culture of SMNs, our laboratory has developed an improved culture system of primary SMNs, which allows cellular models and thus mechanism studies. In the present study, by establishing an in vitro model of spinal cord ischemia, we intended to observe the dynamic time-course changes of SMNs and investigate the role of autophagy in SMNs during the process. It was found that oxygen-glucose deprivation (OGD) resulted in destruction of neural networks and decreased cell viability of primary SMNs, and the severity increased with the prolonging of the OGD time. The OGD treatment enhanced autophagy, which reached a peak at 5 h. Further investigation demonstrated that inhibition of autophagy exacerbated the injury, evidencing that autophagy plays a protective role during the process.
Highlights
The results showed that the proportion of spinal motor neurons (SMNs) reached over 95%, which can meet the requirements of subsequent experiments
Autophagy was first detected by transmission electron microscopy (TEM) in the 1950s, and it was originally observed as a focal degradation of cytoplasmic areas performed by lysosomes, which still remains the hallmarks of this process
The TEM strongly once again suggested that overactivation of autophagy was triggered in primary SMNs subjected to oxygen-glucose deprivation (OGD)
Summary
Spinal cord ischemia is a devastating complication following thoracoabdominal aortic surgery (Drinkwater et al, 2010; Shimizu and Yozu, 2011; Etz et al, 2014), and it frequently occurs as well when the spinal cord suffers from direct trauma during spinal cord injury (Rivlin and Tator, 1978; Aslan et al, 2009), or compression from vertebral stenosis and various other spinal lesions (Gooding et al, 1975; Griffiths et al, 1979; Yang et al, 2015), which may lead to various degrees of disability or even paraparesis/paraplegia (Coselli et al, 1997; Etz et al, 2008; Suarez et al, 2013). Autophagy (means ‘‘self-eating’’ in Greek, ‘‘auto’’ oneself, ‘‘phagy’’ to eat), a term which was first coined by Christian de Duve in 1963 (De Duve, 1963; Klionsky, 2008), is a highly regulated process in which protein aggregates and damaged organelles are degraded via the lysosomal pathway It is an evolutionary conserved catabolic system where unnecessary or dysfunctional cellular components, including cytosolic proteins and organelles, are detained in a double-membrane vesicle, and the resulting vacuoles (autophagosomes) are degraded after they are transmitted to the lysosomal compartment (Klionsky and Emr, 2000; Mizushima and Komatsu, 2011; Feng et al, 2014). The concrete change in a certain cell type during the process of spinal cord injury has never been reported, and the underlying mechanisms deserve further investigation
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