Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke

Noriyuki Matsukawa, Takao Yasuhara, Koichi Hara, Lin Xu, Mina Maki, Guolong Yu, Yuji Kaneko, Kosei Ojika, David C. Hess, Cesar V. Borlongan

研究成果査読

120 被引用数 (Scopus)

抄録

Background: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. Results: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. Conclusion: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.

本文言語English
論文番号1471
ページ(範囲)126
ページ数1
ジャーナルBMC Neuroscience
10
DOI
出版ステータスPublished - 10月 6 2009
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)
  • 細胞および分子神経科学

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