Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

Shiang Suo Huang, Henrich Cheng, Ching Min Tang, Mao Wei Nien, Yuahn Sieh Huang, I. Huei Lee, Jiu Haw Yin, Terry B J Kuo, Cheryl C H Yang, Shen Kou Tsai, Ding I. Yang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Sonic hedgehog (SHH) is a morphogen important for neural development during embryogenesis. Recently, beneficial actions of SHH in ischemic injury have been noted. To test whether epidural application of the biolgically active N-terminal fragment of SHH (SHH-N) may reduce the extent of ischemic brain injury, male Long-Evans rats were exposed to a 60-min episode of middle cerebral artery occlusion (MCAO) with topical application of SHH-N and/or its specific inhibitor, cyclopamine, in fibrin glue over the peri-infarct cortex. We found that epidural application of SHH-N substaintially reduced infarct volumes after 7days of reperfusion, which was reversed by cyclopamine; SHH-N also improved behavioral outcomes as assessed by global neurological functions, rotarod test, and grasping power test. Furthermore, SHH-N attenuated the extents of protein oxidation, lipid peroxidation, and apoptosis induced by focal ischemia/reperfusion. Immunohistochemical staining coupled with bromodeoxyuridine (BrdU) incorporation revealed that SHH-N enhanced post-ischemic angiogenesis, stimulated the proliferation of nestin-positive (nestin+) neural progenitor cells (NPCs), and suppressed astrocytosis. Our results thus revealed multifaceted protective mechanisms of SHH-N against focal cerebral ischemia/reperfusion.

Original languageEnglish
Pages (from-to)680-688
Number of pages9
JournalExperimental Neurology
Volume247
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

Keywords

  • Angiogenesis
  • Anti-apoptosis
  • Anti-oxidation
  • Focal ischemia
  • Middle cerebral artery occlusion

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Huang, S. S., Cheng, H., Tang, C. M., Nien, M. W., Huang, Y. S., Lee, I. H., Yin, J. H., Kuo, T. B. J., Yang, C. C. H., Tsai, S. K., & Yang, D. I. (2013). Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats. Experimental Neurology, 247, 680-688. https://doi.org/10.1016/j.expneurol.2013.03.004