Blockade of Interleukin-6 Receptor Suppresses Reactive Astrogliosis and Ameliorates Functional Recovery in Experimental Spinal Cord Injury

S. Okada, M. Nakamura, Y. Mikami, T. Shimazaki, M. Mihara, Y. Ohsugi, Y. Iwamoto, K. Yoshizaki, T. Kishimoto, Y. Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

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Abstract

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16-1 (100 μg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16-1 not only suppressed the astrocytic diffentiation-promoting effect of IL-6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalJournal of Neuroscience Research
Volume76
Issue number2
DOIs
Publication statusPublished - Apr 15 2004

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Interleukin-6 Receptors
Spinal Cord Injuries
Interleukin-6
Neural Stem Cells
Cicatrix
Stem Cells
Cytokines
Connective Tissue Cells
Neuroglia
Astrocytes
Spinal Cord
Monoclonal Antibodies
Body Weight
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Blockade of Interleukin-6 Receptor Suppresses Reactive Astrogliosis and Ameliorates Functional Recovery in Experimental Spinal Cord Injury. / Okada, S.; Nakamura, M.; Mikami, Y.; Shimazaki, T.; Mihara, M.; Ohsugi, Y.; Iwamoto, Y.; Yoshizaki, K.; Kishimoto, T.; Toyama, Y.; Okano, Hideyuki.

In: Journal of Neuroscience Research, Vol. 76, No. 2, 15.04.2004, p. 265-276.

Research output: Contribution to journalArticle

Okada, S, Nakamura, M, Mikami, Y, Shimazaki, T, Mihara, M, Ohsugi, Y, Iwamoto, Y, Yoshizaki, K, Kishimoto, T, Toyama, Y & Okano, H 2004, 'Blockade of Interleukin-6 Receptor Suppresses Reactive Astrogliosis and Ameliorates Functional Recovery in Experimental Spinal Cord Injury', Journal of Neuroscience Research, vol. 76, no. 2, pp. 265-276. https://doi.org/10.1002/jnr.20044
Okada, S. ; Nakamura, M. ; Mikami, Y. ; Shimazaki, T. ; Mihara, M. ; Ohsugi, Y. ; Iwamoto, Y. ; Yoshizaki, K. ; Kishimoto, T. ; Toyama, Y. ; Okano, Hideyuki. / Blockade of Interleukin-6 Receptor Suppresses Reactive Astrogliosis and Ameliorates Functional Recovery in Experimental Spinal Cord Injury. In: Journal of Neuroscience Research. 2004 ; Vol. 76, No. 2. pp. 265-276.
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