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

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1471
Number of pages1
JournalBMC Neuroscience
Volume10
DOIs
Publication statusPublished - Oct 6 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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    Matsukawa, N., Yasuhara, T., Hara, K., Xu, L., Maki, M., Yu, G., Kaneko, Y., Ojika, K., Hess, D. C., & Borlongan, C. V. (2009). Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neuroscience, 10, [1471]. https://doi.org/10.1186/1471-2202-10-126