Spinal cord injury (SCI) can be caused by external direct or indirect factors, leading to sensory and motor dysfunction in the injured segment and below. SCI causes serious physical and psychological damage to patients, and its complications (such as paralysis and urinary incontinence) can cause considerable economic burden to the society. In Asia, the incidence rate of traumatic SCI ranges from 12.06 to 61.6 per million people. This is slightly lower than North America (27.1 to 83.0 per million people) (Chen et al., 2022).

SCI is divided into primary injury and secondary injury. Secondary SCI has a series of pathophysiological changes, such as increased glutamate excitatory toxicity, mitochondrial disorder, oxidative stress, neuroinflammation, cell apoptosis and necrosis, and axonal degeneration (Scivoletto et al., 2020, Li et al., 2019, Lv et al., 2019). Oxidative stress refers to the imbalance of oxidation-reduction homeostasis, i.e., the imbalance between oxide formation and antioxidant defense system, predominantly leaning towards the oxidation side (Jaganjac et al., 2022). In secondary SCI, augmented glutamate causes ion imbalance and excessive intracellular Ca2+ leads to mitochondrial dysfunction, generating significant reactive oxygen species (ROS) (Zhang et al., 2019). Activated macrophages, neutrophils and oligodendrocytes also release excessive ROS that triggers pro-inflammatory cytokines (TNF-α and IL-2) and protease release, further promoting apoptosis of oligodendrocytes and resulting in axonal demyelination as well as loss of its function and stability (Liu et al., 2020). A higher ROS and reactive nitrogen species (RNS) cause lipid peroxidation and generate reactive aldehydes, such as 4-hydroxynonenal (4-HNE) that are neurotoxic (Ge et al., 2021). SCI upregulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in both neurons and astrocytes. The Nrf2 induces the activity of various antioxidant enzymes, such as heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione peroxidase (GPX) (Lin et al., 2019), which are beneficial for SCI repair. In the clinical setting, dexamethasone and other glucocorticoids are used to improve SCI. However, due to complications arising from the administration of large doses, the use of glucocorticoids has been limited.

Resveratrol is a plant-derived natural polyphenol that acts on a variety of cell targets, such as nuclear factor-κB (NF-κB), AMP-activated protein kinase (AMPK), and silent mating-type information regulation 2 homolog-1 (SIRT1) to exert anti-inflammatory, antioxidant, anti-apoptotic and anti-cancer effects (Zhuang et al., 2019). Resveratrol regulates the activity of related enzymes and inhibit lipid peroxidation. For example, it can activate the SIRT1 signaling to mitigate manganese-induced oxidative stress and neuroinflammation (Cong et al., 2021). Additionally, resveratrol may inhibit oxidative stress by activating the Nrf2/HO-1 signal pathway mediated by the phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt) (Xu et al., 2022). These inhibitory effects can minimize the occurrence and development of oxidative stress after SCI and accelerate the repair process.

This report summarizes the ameliorative effects of resveratrol regarding oxidative stress. The report also elaborates on the Nrf2/HO-1 activation by resveratrol and the specific mechanism of action to attenuate oxidative stress after SCI.