Effects of nerve graft on nitric oxide synthase, NAD(P)H oxidase, and antioxidant enzymes in chronic spinal cord injury

Lee, Yu Shang; Sindhu, Ram K.; Lin, Ching Yi; Ehdaie, Ashkan; Lin, Vernon W.; Vaziri, Nosratola D.

doi:10.1016/j.freeradbiomed.2003.11.006

Cited by 28 publications

(25 citation statements)

References 32 publications

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“…Protein Function Involved in Antioxidant Activity-Large amounts of reactive oxygen species (ROS), including hydrogen peroxide, hydroxyl radicals, and peroxynitrate, are produced within a few hours after spinal cord injury (88,89). These neurotoxic factors contribute to the pathology of secondary damage of spinal cord injury and play an important role in the progression of spinal cord injury (90).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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Acidic fibroblast growth factor (aFGF; also known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. However, the pathological changes that occur with spinal cord injury (SCI) and the attribution to aFGF of a neuroprotective effect during SCI are still elusive. In this study, we demonstrated that rat SCI, when treated with aFGF, showed significant functional recovery as indicated by the Basso, Beattie, and Bresnahan locomotor rating scale and the combined behavior score (p < 0.01-0.001). Furthermore proteomics and bioinformatics approaches were adapted to investigate changes in the global protein profile of the damaged spinal cord tissue when experimental rats were treated either with or without aFGF at 24 h after injury. We found that 51 protein spots, resolvable by two-dimensional PAGE, had significant differential expression. Using hierarchical clustering analysis, these proteins were categorized into five major expression patterns. Noticeably proteins involved in the process of secondary injury, such as astrocyte activation (glial fibrillary acidic protein), inflammation (S100B), and scar formation (keratan sulfate proteoglycan lumican), which lead to the blocking of injured spinal cord regeneration, were down-regulated in the contusive spinal cord after treatment with aFGF. We propose that aFGF might initiate a series of biological processes to prevent or attenuate secondary injury and that this, Spinal cord injury (SCI)1 is a costly disease as well as the most frequent cause of mortality and morbidity in every medical care system around the world (1, 2). Traumatic axonal injury is a primary sequela of contusive SCI and is characterized by axonal swelling and disconnection of the ascending sensory and descending motor tracts (3). Contusive SCI seems to initiate a complicated cascade of pathophysiological changes, a process called secondary injury, including fiber deformation, increased vascular permeability, local ischemia, intraneuronal edema, and local demyelination. Moreover traumatic axonal injury typically involves a disruption of the axonal membrane, and this results in up-regulation of the entry of calcium, the influx of which initiates calpain activation (4, 5) and mitochondrial injury/swelling (6), resulting in cytochrome c release and caspase activation (7). Simultaneously the proliferation and hypertrophy of astrocytes around the injury site are characterized by increased immunoreactivity to glial fibrillary acidic proteins (GFAPs) (8).Although many studies have focused on revealing the pathophysiology of SCI, the exact molecular mechanisms and the biochemical pathways that mediate secondary injury remain sketchy (9). Spinal cord injury often causes permanent neurological deficits mostly because the injured neurons lack regenerative ability, and the series of destructive processes that follow SCI results in a second wave of cell death and spreading tissue loss (10). Therefore, studies of the stimulaFrom the ‡Institute

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Section: Discussionmentioning

confidence: 99%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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“…Components of the NADPH oxidase enzyme and evidence of oxidative stress have been reported to be increased after SCI and remain elevated for chronic periods [9]. The NADPH oxidase enzyme is a protein complex that plays a key role in the production of reactive oxygen species (ROS) and is composed of 4 cytosolic subunits (gp40 PHOX , p47 PHOX , p67 PHOX , and the GTP-binding protein p21-Rac1) and 2 membrane subunits (gp91 PHOX and p22 PHOX ) (FIG.…”

Section: Nadph Oxidasementioning

confidence: 99%

Novel Neuroinflammatory Targets in the Chronically Injured Spinal Cord

Pajoohesh‐Ganji

Byrnes

2011

Neurotherapeutics

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Summary: Injury to the spinal cord is known to result in inflammation. To date, the preponderance of research has focused on the acute neuroinflammatory response, which begins immediately and is believed to terminate within hours to (at most) days after the injury. However, recent studies have demonstrated that postinjury inflammation is not restricted to the first few hours or days after injury, but can last for months to years after a spinal cord injury (SCI). These chronic studies have revealed that increased numbers of inflammatory cells, such as microglia and macrophages, and inflammatory factors, including cytokines, chemokines, and enzyme products are found at markedly delayed times after injury. Here we review experimental work on a selection of the novel inflammatory factors observed chronically after SCI, including the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase enzyme and galectin-3. We will discuss the role of these proteins in inflammation with regard to both detrimental and beneficial effects of neuroinflammation after injury. Finally, the potential of these proteins to serve as therapeutic targets will be considered, and a novel therapeutic approach (i.e., the agonist for metabotropic glutamate receptor 5 [mGluR5], [RS]-2-Chloro-5-hydroxyphenylglycine [CHPG]) will be discussed. This review will demonstrate the expression and activity profiles, roles in potentiation of injury, and therapy studies of these inflammatory factors suggest that not only are these chronically expressed factors viable targets for SCI treatment, but that the therapeutic window is broader than has previously been thought.

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“…In the spinal cord, amyotrophic lateral sclerosis, a neurodegenerative disease affecting motor neurons, is associated with a mutation in the gene encoding CuZnSOD [11]. In spinal cord injury alterations in the antioxidant system have been detected [12], and the inflammatory process is related to oxidative stress at spinal cord [8]. Some works describe changes in antioxidant system after axotomy [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Neuropathic Pain Modifies Antioxidant Activity in Rat Spinal Cord

et al. 2006

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Oxidative stress is an important pathophysiological mechanism of many neurological diseases. Reactive oxygen and nitrogen species have been cited as molecules involved in the nociceptive process. In this study, rats were submitted to sciatic nerve transection (SNT) for induction of neuropathic pain, and enzyme activities of SOD and catalase as well as lipid peroxidation (LPO) were measured in the lumbosacral spinal cord. The results show that LPO was not changed after SNT. SOD activity was reduced 7 days after SNT, while the change in catalase activity occurred on the third and seventh days in both sham and SNT animals. Hyperalgesia in SNT group was detected at the same points in time. These results suggest that SNT was not a strong enough stimulus to deplete all antioxidant content in the spinal cord, since increase in LPO was not detected. However, the role of oxidative stress in nociception can not be excluded.

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Effects of nerve graft on nitric oxide synthase, NAD(P)H oxidase, and antioxidant enzymes in chronic spinal cord injury

Cited by 28 publications

References 32 publications

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Novel Neuroinflammatory Targets in the Chronically Injured Spinal Cord

Neuropathic Pain Modifies Antioxidant Activity in Rat Spinal Cord

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