Role of neutrophils in spinal cord injury in the rat

Taoka, Yuji; Okajima, Kenji; Uchiba, Mitsuhiro; Murakami, Kazunori; Kushimoto, Shigeki; Johno, Masayoshi; Naruo, Masakuni; Okabe, Hiroaki; Takatsuki, Kiyoshi

doi:10.1016/s0306-4522(97)00011-0

Cited by 323 publications

(257 citation statements)

References 22 publications

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“…In this study, we have shown by immunohistochemistry a significant increase in positive staining for TNF-a in SCI mice group compared with sham-operated animal groups as well as FasL. Besides, Taoka et al (1997) showed that activated neutrophils are involved in SCIinduced trauma in rats. We showed that the administration of TRAIL-neutralizing antibody in SCI reduced the expression of both TNF-a and FasL as well as the inflammatory cell infiltration as assessed by the specific granulocyte enzyme MPO after SCI.…”

Section: Discussionsupporting

confidence: 53%

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

Cantarella

Benedetto

Scollo

et al. 2010

Neuropsychopharmacol

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Spinal cord injury (SCI) is a major cause of disability, its clinical outcome depending mostly on the extent of damage in which proapoptotic cytokines have a crucial function. In particular, the inducers of apoptosis belonging to TNF receptor superfamily and their respective ligands are upregulated after SCI. In this study, the function of the proapoptotic cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in SCI-induced damage was investigated in the mouse. SCI resulted in severe trauma, characterized by prominent inflammation-related damage and apoptosis. Immunostaining for TRAIL and its receptor DR5 was found in the white and gray matter of the perilesional area, as also confirmed by western blotting experiments. Immunoneutralization of TRAIL resulted in improved functional recovery, reduced apoptotic cell number, modulation of molecules involved in the inflammatory response (FasL, TNF-a, IL-1b, and MPO), and the corresponding signaling (caspase-8 and -3 activation, JNK phosphorylation, Bax, and Bcl-2 expression). As glucocorticoid-induced TNF receptor superfamily-related protein (GITR) activated by its ligand (GITRL) contributes to SCI-related inflammation, interactions between TRAIL and GITRL were investigated. SCI was associated with upregulated GITR and GITRL expression, a phenomenon prevented by anti-TRAIL treatment. Moreover, the expression of both TRAIL and DR5 was reduced in tissues from mice lacking the GITR gene (GITR À/À ) in comparison with wild-type mice suggesting that TRAIL-and GITRL-activated pathways synergise in the development of SCI-related inflammatory damage. Characterization of new targets within such molecular systems may constitute a platform for innovative treatment of SCI.

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Section: Discussionsupporting

confidence: 53%

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

Cantarella

Benedetto

Scollo

et al. 2010

Neuropsychopharmacol

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“…12 In rats, neutrophils appear at the primary lesion site at 4-6 h after injury, peak in number at 12-24 h and disappear within 5 days. 13,14 Macrophages in the injured spinal cord are derived from blood-borne monocytes and resident microglia. Blood-borne monocyte/ macrophages infiltrate the lesion at 2 days after SCI in rats, achieve their highest density at 5-7 days and persist for weeks to months.…”

Section: Discussionmentioning

confidence: 99%

Responses of microRNAs 124a and 223 following spinal cord injury in mice

et al. 2009

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Study design: We investigated microRNA (miRNA) expression after spinal cord injury (SCI) in mice. Objectives: The recent discovery of miRNAs suggests a novel regulatory control over gene expression during plant and animal development. MiRNAs are short noncoding RNAs that suppress the translation of target genes by binding to their mRNAs, and play a central role in gene regulation in health and disease. The purpose of this study was to examine miRNA expression after SCI. Setting: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University. Methods: We examined the expression of miRNA (miR)-223 and miR-124a in a mouse model at 6 h, 12 h, 1 day, 3 days and 7 days after SCI using quantitative PCR. The miRNA expression was confirmed by in situ hybridization. Results: Quantitative PCR revealed two peaks of miR-223 expression at 6 and 12 h and 3 days after SCI. MiR-124a expression decreased significantly from 1 day to 7 days after SCI. In situ hybridization demonstrated the presence of miR-223 around the injured site. However, miR-124a, which was present in the normal spinal cord, was not observed at the injured site. Conclusion: Our results indicate a time-dependent expression pattern of miR-223 and miR-124a in a mouse model of SCI. In this study, the time course of miRNA-223 expression may be related to inflammatory responses after SCI, and the time course of decreased miR-124a expression may reflect cell death.

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“…An acute inflammatory response at the site of the initial lesion is at least partly responsible for this secondary spinal cord pathology (e.g., refs. [2][3][4]. Among the inflammatory cells recruited to the injured area are macrophages͞microglia and neutrophils that can mediate tissue damage by producing a variety of cytotoxic factors including reactive nitrogen species (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Uric acid protects against secondary damage after spinal cord injury

Scott

Cuzzocrea

Genovese

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

114

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Peroxynitrite contributes to the pathogenesis of various neurodegenerative disorders through multiple mechanisms and is thought to mediate secondary neuronal cell death after spinal cord injury (SCI). Here we establish that physiologically relevant levels of uric acid (UA), a selective inhibitor of certain peroxynitrite-mediated reactions, block the toxic effects of peroxynitrite on primary spinal cord neurons in vitro. Furthermore, administration of UA at the onset of SCI in a mouse model inhibits several pathological changes in the spinal cord including general tissue damage, nitrotyrosine formation, lipid peroxidation, activation of poly(ADP-ribose) polymerase, and neutrophil invasion. More importantly, UA treatment improves functional recovery from the injury. Taken together, our findings support the concept that peroxynitrite contributes to the pathophysiology of secondary damage after SCI. They also raise the possibility that elevating UA levels may provide a therapeutic approach for the treatment of SCI as well as other neurological diseases with a peroxynitrite-mediated pathological component.blood-brain barrier ͉ neutrophils ͉ peroxynitrite ͉ spinal cord neurons ͉ cytotoxicity A cascade of pathophysiological processes rapidly follows mechanical trauma to the spinal cord, resulting in secondary neuronal damage that can significantly exacerbate the original injury (1). An acute inflammatory response at the site of the initial lesion is at least partly responsible for this secondary spinal cord pathology (e.g., refs. 2-4). Among the inflammatory cells recruited to the injured area are macrophages͞microglia and neutrophils that can mediate tissue damage by producing a variety of cytotoxic factors including reactive nitrogen species (3-7). Several studies have implicated peroxynitrite, a molecule generated when nitric oxide and superoxide combine, in secondary neuronal damage after spinal cord injury (SCI) (5-7). Not only has evidence of peroxynitrite production been detected in spinal cord tissues from rats after traumatic injury (5-7), but administration of a peroxynitrite donor directly into the rat spinal cord has been shown to cause neuronal cell death and neurological deficit (8). In addition, a number of previous reports have demonstrated that peroxynitrite is toxic for neurons, including primary spinal cord neurons, and neuronal cell lines in vitro (9-13).Peroxynitrite is known to mediate several potentially destructive chemical reactions, including tyrosine nitration and lipid peroxidation (14). Mitochondrial respiration is directly inhibited by peroxynitrite and is an early marker of its cytotoxic effects (9,14). In addition, peroxynitrite causes DNA strand breakage, which activates the enzyme poly(ADP-ribose) polymerase (PARP), which in turn triggers a cascade of processes that often lead to cell death (14). Because increased nitrotyrosine formation, lipid peroxidation, and PARP activation have all been associated with secondary damage in spinal cord trauma (5-7, 14-20), it is possible that second...

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Role of neutrophils in spinal cord injury in the rat

Cited by 323 publications

References 22 publications

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

Neutralization of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Reduces Spinal Cord Injury Damage in Mice

Responses of microRNAs 124a and 223 following spinal cord injury in mice

Uric acid protects against secondary damage after spinal cord injury

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