9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein
✍ Scribed by Hui Shen; Yu Luo; Chi-Chung Kuo; Xiaolin Deng; Chen-Fu Chang; Brandon K. Harvey; Barry J. Hoffer; Yun Wang
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 500 KB
- Volume
- 87
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H~2~O~2~ 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 ligation. 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. © 2008 Wiley‐Liss, Inc.