9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein

Hui Shen, Yu Luo, Chi Chung Kuo, Xiaolin Deng, Chen Fu Fang, Brandon K. Harvey, Barry J. Hoffer, Yun Wang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligatiom 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia-induced injury, and these effects involve BMPs.

Original languageEnglish
Pages (from-to)545-555
Number of pages11
JournalJournal of Neuroscience Research
Volume87
Issue number2
DOIs
Publication statusPublished - Feb 1 2009
Externally publishedYes

Keywords

  • BMP7
  • Neuroprotection
  • Retinoic acid
  • Stroke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Shen, H., Luo, Y., Kuo, C. C., Deng, X., Fang, C. F., Harvey, B. K., Hoffer, B. J., & Wang, Y. (2009). 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein. Journal of Neuroscience Research, 87(2), 545-555. https://doi.org/10.1002/jnr.21865