Targeting Mitochondrial Oxidative Stress: Potential Neuroprotective Therapy for Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a serious central nervous system (CNS) injury disease related to hypoxia-ischemia and inflammation. It is characterized by excessive reactive oxygen species (ROS) production, oxidative damage to nerve cells, and mitochondrial dysfunction. Mitochondria serve as the primary cellular origin of ROS, wherein the electron transfer chain complexes within oxidative phosphorylation frequently encounter electron leakage. These leaked electrons react with molecular oxygen, engendering the production of ROS, which culminates in the occurrence of oxidative stress. Oxidative stress is one of the common forms of secondary injury after SCI. Mitochondrial oxidative stress can lead to impaired mitochondrial function and disrupt cellular signal transduction pathways. Hence, restoring mitochondrial electron transport chain (ETC), reducing ROS production and enhancing mitochondrial function may be potential strategies for the treatment of SCI. This article focuses on the pathophysiological role of mitochondrial oxidative stress in SCI and evaluates in detail the neuroprotective effects of various mitochondrial-targeted antioxidant therapies in SCI, including both drug and non-drug therapy. The objective is to provide valuable insights and serve as a valuable reference for future research in the field of SCI.

Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis

“…Based on the data presented in Figure 3D, the MiT group contributes with more cells to CAP recordings than the MiP and CI groups. These results suggest that MitoTEMPO administered post-injury, as demonstrated in other studies, exerts an antioxidant effect within the mitochondria, supporting the necessary ATP synthesis for axonal regeneration [39]. Consequently, this facilitates a greater contribution of nerve axons to compound action potential, as indicated.…”

Mitochondrial Reactive Oxygen Species in Infection and Immunity

“…However, elevated levels of ROS are associated with a wide range of diseases, like cancer, neurodegeneration, and cardiac disorders [ 21 , 22 , 23 ]. Likewise, an excess of mitochondrial ROS (mt-ROS) is also implicated in a plethora of diseases and conditions, such as ischemia and tumorigenesis [ 24 , 25 ]. The importance of countering oxidative stress is evidenced by the antioxidant defense machinery employed by the cells.…”