Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia

Haruyuki Suzuki, Yoshihisa Sugimura, Shintaro Iwama, Hiromi Suzuki, Ozaki Nobuaki, Hiroshi Nagasaki, Hiroshi Arima, Makoto Sawada, Yutaka Oiso

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (e.g. IL-1β, inducible nitric-oxide synthase, and TNF-α), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice.

Original languageEnglish
Pages (from-to)2090-2098
Number of pages9
JournalJournal of the American Society of Nephrology
Volume21
Issue number12
DOIs
Publication statusPublished - 01-12-2010

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Minocycline
Microglia
Demyelinating Diseases
Hyponatremia
Nervous System
Matrix Metalloproteinase 12
Cytokines
Chemokine CCL2
Nitric Oxide Synthase Type II
Interleukin-1
Real-Time Polymerase Chain Reaction
Diet
Therapeutics

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Suzuki, Haruyuki ; Sugimura, Yoshihisa ; Iwama, Shintaro ; Suzuki, Hiromi ; Nobuaki, Ozaki ; Nagasaki, Hiroshi ; Arima, Hiroshi ; Sawada, Makoto ; Oiso, Yutaka. / Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia. In: Journal of the American Society of Nephrology. 2010 ; Vol. 21, No. 12. pp. 2090-2098.
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Suzuki, H, Sugimura, Y, Iwama, S, Suzuki, H, Nobuaki, O, Nagasaki, H, Arima, H, Sawada, M & Oiso, Y 2010, 'Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia', Journal of the American Society of Nephrology, vol. 21, no. 12, pp. 2090-2098. https://doi.org/10.1681/ASN.2010040438

Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia. / Suzuki, Haruyuki; Sugimura, Yoshihisa; Iwama, Shintaro; Suzuki, Hiromi; Nobuaki, Ozaki; Nagasaki, Hiroshi; Arima, Hiroshi; Sawada, Makoto; Oiso, Yutaka.

In: Journal of the American Society of Nephrology, Vol. 21, No. 12, 01.12.2010, p. 2090-2098.

Research output: Contribution to journalArticle

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