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Following spinal cord trauma, mitochondrial dysfunction associated with increased oxidative stress is a critical event leading to leukocyte inflammatory responses, neuronal cell death and demyelination, contributing to permanent locomotor and neurological disability. The present study demonstrated that the mitochondrial enhancer N-acetylcysteine (NAC) may restore redox balance via enhancement of mitochondrial respiratory activity following traumatic spinal cord injury (SCI). In addition, NAC ameliorates oxidative stress-induced neuronal loss, demyelination, leukocyte infiltration and inflammatory mediator expression and improves long-term locomotor function. Furthermore, neuronal survival and neurological recovery are significantly correlated with increased mitochondrial bioenergetics in SCI following treatment with NAC. Therefore, NAC may represent a potential therapeutic agent for preserving mitochondrial dynamics and integrity following traumatic SCI.

After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord‑injured mice following blockade of ETAR and ETBR. We also examined the post‑traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord‑injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord‑injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long‑term neurological recovery.