Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury

Amar, Arun Paul; Levy, Michael L.

doi:10.1097/00006123-199905000-00052

Cited by 357 publications

(244 citation statements)

References 88 publications

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“…[1][2][3][4][5][6][7][8][9][14][15][16][17][18][19][20] Some of these events, together constituting the 'secondary injury', evolve very early after the trauma.…”

Section: Literature Reviewmentioning

confidence: 99%

“…The traumatic event initiates a cascade of secondary injury mechanisms such as vascular changes, electrolytes shifts, excitotoxic neurotransmitters accumulation, inflammation, loss of energy metabolism, etc. [1][2][3][4][5][6][7][8][9] The persistent compression of spinal cord represents a cause of secondary injury potentially reversible. 10 The comprehension of these pathophysiological mechanisms has led to the studies of the National Acute Spinal Cord Injury Study (NASCIS) group on the use of high-dose methyl-prednisolone.…”

Section: Introductionmentioning

confidence: 99%

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Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach

et al. 2004

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Study design: Definitive and unequivocal evidence to support the practice of early or late surgery is still lacking in clinical studies. Accordingly, meta-analysis is one of the few methods that offer a rational, statistical approach to management decision. A review of the clinical literature on spinal cord injury with emphasis on the role of early surgical decompression and a meta-analysis of results was performed. Objectives: To determine whether neurological outcome is improved in traumatic spinal cordinjured patients who had surgery within 24 h as compared with those who had late surgery or conservative treatment. Methods: A Medline search covering the period 1966-2000, supplemented with manual search, was used to locate studies containing information on indication, rationale and timing of surgical decompression after spinal cord injuries. The analysis included a total of 1687 eligible patients. Results: Statistically, early decompression resulted in better outcome compared with both conservative (Po0.001) and late management (Po0.001). Nevertheless, analysis of homogeneity showed that only data regarding patients with incomplete neurological deficits who had early surgery were reliable. Conclusions: Although statistically the percentage of patients with incomplete neurological deficits improving after early decompression appear 89.7% (95% confidence interval: 83.9, 95.5%), to be better than with the other modes of treatment when taking into consideration the material available for analysis and the various other factors including clinical limitations; early surgical decompression can only be considered as practice option for all groups of patients.

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“…[1][2][3][4][5][6][7][8][9][14][15][16][17][18][19][20] Some of these events, together constituting the 'secondary injury', evolve very early after the trauma.…”

Section: Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach

et al. 2004

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“…The primary traumatic mechanical injury to the spinal cord causes the death of a number of neurons that can neither be recovered nor regenerated. However, neurons continue to die for hours after SCI and this represents a potentially avoidable event [3]. In particular, this secondary neuronal death is determined by a large number of cellular and molecular events (characteristic of local inflammatory response) that have been proposed to contribute significantly to secondary damage in the injured spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

et al. 2012

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Spinal cord injury (SCI) is a traumatic event that causes a secondary and extended inflammation characterized by infiltration of immune cells, including T lymphocytes, release of pro-inflammatory mediators in the lesion site, and tissue degeneration. Current therapeutic approaches for SCI are limited to glucocorticoids (GC) due to their potent antiinflammatory activity. GC efficacy resides, in part, in the capability to inhibit NF-κB, T lymphocyte activation, and the consequent cytokine production. In this study, we performed experiments aimed to test the susceptibility of glucocorticoidinduced leucine zipper (GILZ) transgenic (GILZ TG ) mice, in which GILZ is selectively over-expressed in T lymphocytes, to SCI induction. Consistent with a decreased inflammatory response, GILZ TG were less susceptible to SCI as compared to wild-type littermates. Notably, inhibition of NF-κB activation and nuclear translocation, diminished T lymphocytes activation and tissue infiltration, as well as decreased release of cytokines were evident in GILZ TG as compared to wild-type mice. Moreover, GILZ TG showed a reduced tumor necrosis factor-α, IL-1β, Inductible nitric oxide synthase (iNOS) and nytrotyrosine production, apoptosis, and neuronal tissue damage. Together these results indicate that GILZ mimics the anti-inflammatory effect of GC and represents a potential pharmacological target for modulation of T lymphocyte-mediated immune response in inflammatory disorders, such as SCI.

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“…Reactive oxygen species (ROS) are important mediators of SCI. 6 One such ROS, namely NO, has major cytotoxic effects within the secondary lesion. 7 For example, peroxynitrite is a superoxide derivative of NO that has been shown to destroy proteins, lipids, and DNA.…”

Section: Introductionmentioning

confidence: 99%

Changes in nitric oxide synthase expression in young and adult rats after spinal cord injury

2007

Spinal Cord

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Objective: To examine the clinical meaning of the changes in nitric oxide synthase (NOS) expression and activity after spinal cord injury (SCI) according to the age of the experiment animal. Material and method: Ten 5-and 16-week-old Sprague-Dawley rats were laminectomized at T10 and SCI induced at this level using a New York impactor. Outcome measures to assess SCI utilized the Basso-Beatti-Bresnahan scale to quantitate hind limb motor dysfunction as a functional outcome measure. NOS isoforms (nNOS, neuronal NOS; iNOS, inducible NOS; and eNOS, endothelial NOS) were also immunolocalized in sections of control and spinal cord injury in the two sample groups using specific monoclonal antibodies. Student's t-test evaluated the difference between the young and adult rats, and Po0.05 was considered as significant value. Result: As the expression of nNOS on the spinal gray matter of the adult rat decreased, eNOS activity increased. Different from the adult rat, expression of the nNOS in the young rat was maintained until 1 day after SCI, and compared with the adult rat; eNOS activity was increased in the vessels from the damaged gray matter area after 7 days of SCI. iNOS expression was maintained until the 7th day of SCI on the adult rat, but iNOS expression after 7 days of SCI on young rat decreased. The young rat showed relatively less motor disability on the hind limb when compared with the adult rat, and had a rapid recovery. Conclusion: Neural protective eNOS activity increased after SCI in the young rat, and neural destructive iNOS expression was more remarkable in the adult rat.

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Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury

Cited by 357 publications

References 88 publications

Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach

Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach

Glucocorticoid-Induced Leucine Zipper (GILZ) Over-Expression in T Lymphocytes Inhibits Inflammation and Tissue Damage in Spinal Cord Injury

Changes in nitric oxide synthase expression in young and adult rats after spinal cord injury

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