Secondary injury (SI) after spinal cord trauma is characterized by the multiple pathophysiological events that are set in motion by a primary mechanical insult to the spinal cord. SI produces a post-spinal cord injury (SCI) microenvironment that severely limits recovery, and results in more functional deficits. Many advances have been made to increase the scientific understanding of SI mechanisms, but there remains a lack of standardized clinical treatment to mitigate the damage caused by secondary pathophysiology. The classification of SI processes can be done based on the biological systems they take place: vascular (hemorrhagic necrosis, ischemia, edema), immune (cytokine and hormone release, residential inflammatory cells, peripheral inflammatory and immune cells), and neuronal/glial systems (excitotoxicity, mitochondrial dysfunction, ionic disturbances, overproduction of reactive oxygen and nitrogen species, cell death pathway activation, and axon degeneration). Regarding mechanisms underlying the SI processes (i.e., SI mechanisms: the biochemical events that exacerbate structural and functional losses), SCI-induced elevation of reactive oxygen and reactive nitrogen species (ROS/RNS) serve as one of the most potent triggers of neural cell and neurite death and inflammation, essentially affecting all aforementioned systems to worsen neurological dysfunction. In addition to the role in pathophysiological circumstances, ROS/RNS are also important players in mediating physiological functions (e.g., cell signaling). This feature requires that development of therapeutics for managing post-SCI ROS and RNS must specifically impede the detrimental effects of the radicals in propagating the SI scale without interfering with their physiological roles. In the context of SCI, regulation of ROS/RNS species at their homeostatic levels may serve as an effective therapeutic target for future clinical studies to mitigate neurodegeneration and neuroinflammation, and to promote a permissive environment for endogenous recovery. Based on these facts, Hydrogen Peroxide and Peroxynitrite (a representative ROS and RNS, respectively) were evaluated as SI mediators after SCI and for their potential to be targeted to develop interventions to treat SCI. Overall, the reviewed research findings suggested that oxidative damage cascades should be further studied in laboratory and clinical settings to advance understanding of SI processes of SCI for devising therapies. / 2025-02-03T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45582 |
| Date | 04 February 2023 |
| Creators | Arbelaez, Christian Alexander |
| Contributors | Soghomonian, Jean-Jacques, Teng, Yang |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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