Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

Tuna, Metin; Polat, Sait; Erman, Tahsin; İldan, Faruk; Göçer, A. İskender; Tuna, Nusa; Tamer, Lülüfer; Kaya, Müge Mavioğlu; Çetinalp, Erdal

doi:10.3171/spi.2001.95.1.0064

Cited by 29 publications

(27 citation statements)

References 77 publications

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“…3; Bartholdi and Schwab, 1997;Kossmann et al, 1999;Hayashi et al, 2000;Nesic et al, 2001). While SCI-induced TNF␣ and IL-1␤ increases are reported to be deleterious in SCI (Bethea et al, 1999;Nesic et al, 2001), IL-6 may be protective (Tuna et al, 2001). SCI induces up-regulation of cytokines and chemokines (McTigue et al, 1998; Table IV) which then stimulate endothelial cells to mediate neutrophil, monocyte and T-cell attachment, excarberating SCI-induced cell losses (McTigue et al, 2000).…”

Section: Discussion Expression Profile Of the Contused Spinal Cord Onmentioning

confidence: 99%

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Nešić

Švrakić

et al. 2002

J of Neuroscience Research

102

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Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate ) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome.

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Section: Discussion Expression Profile Of the Contused Spinal Cord Onmentioning

confidence: 99%

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Nešić

Švrakić

et al. 2002

J of Neuroscience Research

102

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“…Membranebound enzymes like Na + ,K + -ATPase require phospholipids for maintenance of their activity and are very susceptible to structural changes due to lipid peroxidation [38,39] . Therefore, assessment of the Na + ,K + -ATPase activity can be used as an index for oxidant-induced tissue injury and lipid peroxidation [40] . This can be an explanation for why gastric injury was accompanied by a simultan eous increase in MDA and a decrease in Na + ,K + -ATPase activity in the current study.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Effect of Alpha-Lipoic Acid against Ethanol-Induced Gastric Mucosal Erosion in Rats

Şehirli¹,

Tatlıdede²,

Yüksel³

et al. 2007

Pharmacology

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Background/Aims: This investigation elucidates the role of free radicals in ethanol-induced gastric mucosal erosion and the protective effect of lipoic acid. Methods: After overnight fasting, Wistar albino rats were orally treated with 1 ml of absolute ethanol to induce gastric erosion. Lipoic acid (100 mg/kg) was given orally for 3 days before ethanol administration. Mucosal damage was evaluated 1 h after ethanol administration by macroscopic examination and histological analysis. Additional tissue samples were taken for measurement of malondialdehyde, glutathione (GSH), and myeloperoxidase activity. Production of reactive oxidants and oxidant-induced DNA fragmentation and Na⁺,K⁺-ATPase activity were also assayed in the tissue samples. Results: Generation of reactive oxygen species and lipid peroxidation associated with neutrophil infiltration play an important role in the pathogenesis of gastric mucosal damage induced by ethanol. Furthermore, oxidants depleted tissue GSH stores and impaired membrane structure as Na⁺,K⁺-ATPase activity was inhibited. On the other hand, lipoic acid treatment reversed all these biochemical indices as well as the histopathological changes induced by ethanol. Conclusion: These data suggest that lipoic acid administration effectively counteracts the deleterious effect of ethanol-induced gastric mucosal injury and attenuates gastric damage through its antioxidant effects.

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“…Conversely, IL-6 KO mice are resistant to experimental allergic encephalomyelitis (EAE) (7), and IL-6-neutralizing antibodies reduce EAE in wild-type mice (8), suggesting a role for IL-6 in mediating autoimmune demyelination. Neutralization of CNS IL-6 attenuates traumatic spinal cord injury in rats and is associated with reduced iNOS activity (9). As has been seen in other tissues (10), IL-6 within the CNS may stimulate iNOS expression, resulting in the production of NO and leading to free radical-induced tissue injury (10).…”

Section: Introductionmentioning

confidence: 99%

IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis

Kaplin

Deshpande

Scott

et al. 2005

Journal of Clinical Investigation

115

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Transverse myelitis (TM) is an immune-mediated spinal cord disorder associated with inflammation, demyelination, and axonal damage. We investigated the soluble immune derangements present in TM patients and found that IL-6 levels were selectively and dramatically elevated in the cerebrospinal fluid and directly correlated with markers of tissue injury and sustained clinical disability. IL-6 was necessary and sufficient to mediate cellular injury in spinal cord organotypic tissue culture sections through activation of the JAK/STAT pathway, resulting in increased activity of iNOS and poly(ADP-ribose) polymerase (PARP). Rats intrathecally infused with IL-6 developed progressive weakness and spinal cord inflammation, demyelination, and axonal damage, which were blocked by PARP inhibition. Addition of IL-6 to brain organotypic cultures or into the cerebral ventricles of adult rats did not activate the JAK/STAT pathway, which is potentially due to increased expression of soluble IL-6 receptor in the brain relative to the spinal cord that may antagonize IL-6 signaling in this context. The spatially distinct responses to IL-6 may underlie regional vulnerability of different parts of the CNS to inflammatory injury. The elucidation of this pathway identifies specific therapeutic targets in the management of CNS autoimmune conditions.

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Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

Cited by 29 publications

References 77 publications

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Antioxidant Effect of Alpha-Lipoic Acid against Ethanol-Induced Gastric Mucosal Erosion in Rats

IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis

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