Table 1.

Molecular therapies for spinal cord injury.

Therapeutic Agent	Molecular Target	Mechanisms of Action	Reference
Diazoxide	K-ATP Channels	Aids spinal cord ischemia-reperfusion injury by decreasing apoptosis and preserving neuronal viability and motor function. The synergistic effect with erythropoietin contributes to higher therapeutic effects.	[109,110,111,112]
Glibenclamide	NCCa-ATP	Acts as an NCCa-ATP antagonist, improving behavioral outcomes, decreasing lesion volume, and significantly preserving white matter.	[113]
Levetiracetam	SV2A	Reduces glutamate excitotoxicity, lipid peroxidation, and apoptosis, and improves astrocitic function. Significant functional and histological improvements were observed.	[115,116]
Riluzole	Na+ Channels	Reduces glutamate excitotoxicity and inflammatory cytokines, and induces a less active state in microglia and macrophages. Decreases cavity size and neuropathic pain, and improves motor function recovery.	[118,119,121,122,123]
Progesterone	PR	Increases TGFβ1 positive astrocytes and microglia cells. Attenuates axonal dieback, neuronal death, and pro-inflammatory cytokines. Contradictory results were observed.	[134,135,136,137,250]
Estrogen	ER-α and ER-β receptors	Attenuates the expression of several inflammasome components, apoptosis, and ROS production. Reduces glial scar formation and demyelination, and improves axonal regeneration.	[138,144,145,146]
Atorvastatin	HMG-CoA reductase inhibitor	Reduces oxidative stress markers, pro-inflammatory cytokines, and apoptosis. Improve motor functions and increase spare axons. Synergic treatment with and L-carnitine enhances therapeutic outcomes. No improvements were observed when tested in humans aside from a decrease in neuropathic pain.	[148,150,151,152,153,154]
Resveratrol	Pleiotropic interactions	Activates autophagy and inhibits apoptosis and pro-inflammatory cytokines. Reduces astrocyte activation and glial scar formation. Improves motor function and survival of motor neurons.	[161,163,164,165,166,167,168,169]
Omega-3 fatty acids	Pleiotropic interactions	Reduces oxidative stress, apoptosis, and inflammatory markers, and increases autophagy. Inhibits microgliosis and demyelination and increases oligodendrocytes. Locomotor recovery was observed.	[16,176,177,178,179,180,251]
Minocycline	Pleiotropic interactions	Improves behavior outcomes. Reduction in free radicals, lipid peroxidation, glial fibrillary, and acidic protein expression, as well as an increase in brain-derived neurotrophic factor were observed. Synergic effects with olfactory ensheathing cells graft were observed.	[185,186,187,188]
Il-10	IL-10R1 and IL-10R 2	Improves motor function, reduces lesion volume, decreases TNF-α levels and modulation of macrophages.	[252,253]
IL-4	IL-4Rα	Reduction in tissue damage and inflammatory markers were observed. Favors macrophage and microglia phenotype to a pro-regenerative phenotype. Improves locomotor recovery.	[205,206,254]
Maresin	RORα/LGR6	Reduces pro-inflammatory cytokines, induces pro-regenerative macrophages phenotype, improves neutrophil clearance, and reduces macrophages in the lesion site. Improves locomotor recovery.	[210,255]
Hypothermia	-	Reduces inflammatory cell infiltration, cell death, MPO activity, and vasogenic edema, and increases BSCB stabilization.	[214]
Anti-Nogo A	Nogo-A receptor	Promotes axonal regrowth and sprouting. Improves functional recovery, and reduces urodynamic abnormalities.	[220,225,226,227,228]
ChABC	CSPGs	Promotes functional recovery, neural plasticity, and regeneration. Synergic treatment with cell therapies.	[232,236,237,245,246,247,248,249]