Reduction of ischemia-induced cerebral injury by all-trans-retinoic acid.
Ischemia-induced cerebral injury evolves over a longer period than previously believed through post-ischemic inflammation. Retinoic acid (RA) has been shown to exert cytoprotective effects on several cells, but its effects on ischemia-induced cerebral injury have been poorly characterized. The aim of the present study was to examine the effects of all-trans-RA on ischemia-induced cerebral injury and elucidate the underlying mechanism. All-trans-RA treatment reduced the size of the ischemia-induced cerebral infarct. To elucidate the underlying mechanism, ischemia-induced cerebral inflammation was studied by examination of expressions of interleukin 1beta (IL-1beta) and ED-1. RA treatment significantly reduced the cerebral inflammation. Moreover, cerebral ischemic induction of cyclooxygenase-2 (COX-2) and CCAAT/enhancer binding protein beta (C/EBPbeta), which binds to the COX-2 promoter, was also inhibited by RA. These results suggest that RA can reduce ischemia-induced cerebral injury by an anti-inflammatory action, which may be effected via inhibition of C/EBPbeta-mediated COX-2 induction.
Choi
Byung-Kwan
BK
Department of Neurosurgery, Pusan National University, 1-10 Ami-Dong, Suh-Gu, Busan 602-739, South Korea.
Kim
Ji-Hoon
JH
Jung
Jong-Soo
JS
Lee
Young-Suk
YS
Han
Myoung-Eun
ME
Baek
Sun-Yong
SY
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Oh
Sae-Ock
SO
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053331:Ectodysplasins / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D010784:Photomicrography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; D053331:Ectodysplasins; D053583:Interleukin-1beta; D014212:Tretinoin; D051546:Cyclooxygenase 2