Table 1.

Induction of autophagy for neuroprotection and functional recovery in traumatic SCI

Inducer of autophagy	Type of SCI model	Mechanisms and outcomes	Reference(s)
Rapamycin	Acute traumatic SCI in mice and rats	Inhibition of mTOR signaling promoted autophagy with upregulation of Beclin-1 and LC3B II, reduced neuronal apoptosis, and significantly increased locomotor function.	Sekiguchi et al., 2012; Wang et al., 2014
Rapamycin	Acute traumatic SCI in mice	Activation of autophagy flux (degradation of p62/SQSTM1 and p70S6K), decreases in macrophage/neutrophil infiltration and microglia activation, inflammation, astrocyte proliferation, and increase in p-Akt promoted neuronal survival and axonogenesis.	Goldshmit et al., 2015
VEGF165	Acute and subacute traumatic SCI in rats	Increases in the autophagy biomarkers Beclin-1 and LC3B II and decreases in inflammatory factors (IL-1β, TNF-α, and IL-10) and loss of motoneurons promoted locomotor function.	Wang et al., 2015
Retinoic acid	Subacute traumatic SCI in rats	Activation of autophagy flux with increase in LC3B II and decrease in p62, reduction in BSCB permeability and loss of tight junction molecules (P120, β-catenin, occludin, and claudin5) improved functional recovery.	Zhou et al., 2016
Metformin	Acute and subacute traumatic SCI in rats	Stimulation of autophagy flux with increases in Beclin-1 and LC3B II and decreases in p62 and inhibition of apoptosis promoted functional recovery.	Zhang et al., 2017
Atorvastatin	Acute, subacute, and chronic traumatic SCI in rats	Activation of autophagy (increases in Beclin-1 and LC3B II) and inhibition of apoptosis (deceases in caspase-9 and caspase-3) promoted recovery of neurological function.	Gao et al., 2016
Resveratrol	Acute and subacute traumatic SCI in rats	Activation of AMPK/SIRT1 signaling pathway promoted autophagy (increases in Beclin-1 and LC3B II), inhibited apoptosis (decreases in Bax and active caspase-9 and caspase-3), and provided functional neuroprotection.	Zhao et al., 2017
Curcumin	Acute and subacute traumatic SCI in rats	Increases in autophagy (inhibition of Akt/mTOR signaling pathway), spinal cord integrity, and remyelination, and prevention of apoptosis and inflammation promoted functional recovery.	Li et al., 2019a
FG-4592 or dimethyloxalylglycine	Acute and subacute traumatic SCI in rats	Activation of autophagy via HIF-1α/BNIP3 signaling pathway promoted neuroprotection, and axonal regeneration and improved functional recovery.	Wu et al., 2016; Li et al., 2019b

AMPK: Adenosine 5′ monophosphate-activated protein kinase; BNIP3: Bcl-2 and adenovirus E1B 19-kDa interacting protein 3; BSCB: blood-spinal cord barrier; HIF-1α: hypoxia inducible factor-1α; IL: interleukin; LC3B II: microtubule-associated protein 1 light chain 3B; mTOR: mechanistic target of rapamycin; SCI: spinal cord injury; SIRT1: Sirtuin 1; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor.