The Temporal Pattern, Flux, and Function of Autophagy in Spinal Cord Injury

Abstract

Previous studies have indicated that autophagy plays a critical role in spinal cord injury (SCI), including traumatic spinal cord injury (TSCI) and ischemia-reperfusion spinal cord injury (IRSCI). However, while the understanding of mechanisms underlying autophagy in SCI has progressed, there remain several controversial points: (1) temporal pattern results of autophagic activation after SCI are not consistent across studies; (2) effect of accumulation of autophagosomes due to the blockade or enhancement of autophagic flux is uncertain; (3) overall effect of enhanced autophagy remains undefined, with both beneficial and detrimental outcomes reported in SCI literature. In this review, the temporal pattern of autophagic activation, autophagic flux, autophagic cell death, relationship between autophagy and apoptosis, and pharmacological intervention of autophagy in TSCI (contusion injury, compression injury and hemisection injury) and IRSCI are discussed. Types of SCI and severity appear to contribute to differences in outcomes regarding temporal pattern, flux, and function of autophagy. With future development of specific strategies on autophagy intervention, autophagy may play an important role in improving functional recovery in patients with SCI.

AMP‐activated protein kinase‐dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats

“…Previous studies employing spinal cord contusion injury model have shown that levels of LC3 and Beclin 1 were increased and peaked at 7 or 10 days after injury, while studies employing hemi‐section injury model showed that the increase in LC3 signals was detected as early as 4 hours and peaked at 3 days after hemi‐section injury. The inconsistency of temporal pattern of autophagy following SCI could be prompted by the difference in SCI models or injury severity. Under our experimental condition, autophagic activity was significantly enhanced after SCI, peaked at 3 days, and fell slightly at 7 days after injury.…”

Resveratrol ameliorates autophagic flux to promote functional recovery in rats after spinal cord injury

“…The primary injury, which is irreversible, means that the spinal cord is injured by a direct or indirect violence. However, the secondary injury, following the primary injury, causes a sustained injury at the molecular and cellular level surrounding the epicenter of the lesion, including edema, hemorrhage, apoptosis, inflammation and oxidative stress, significantly affecting the prognosis of SCI [ 3 – 5 ]. It is considered as an effective method to treat SCI by reducing the secondary injury.…”

A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells

“…The term “autophagic flux” describe that autophagy is a dynamic process (Zhou et al, 2017 ), and there is a dynamic equilibrium between autophagosome formation and clearance by lysosome. Actually, the rate at which material is cleared from the cell by autophagy is known as autophagy flux (Palumbo et al, 2016 ).…”