Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion.
Inflammation, which is known to be detrimental to the neurological outcome during the acute phase after ischemia, provides a potential preventative or therapeutic approach for acute stroke. Lipoxins are endogenous lipoxygenase derived eicosanoids and evokes protective actions in a range of pathophysiologic processes. Here, we evaluated the efficacy of 5 (S), 6 (R)-lipoxin A(4) methyl ester (LXA(4) ME), a stable synthetic analogue of lipoxin A(4) in cerebral ischemia reperfusion injury in rats. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2h. Intracerebroventricular administration of LXA(4) ME immediately after onset of ischemia ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal apoptosis. Moreover, Treatment with LXA(4) ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-alpha and IL-1beta; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-beta1 in the ischemic brain. In addition, activation of NF-kappaBeta was inhibited by LXA(4) ME treatment. These results demonstrate that treatment of LXA(4) ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.
Ye
Xi-Hong
XH
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wu
Yan
Y
Guo
Pei-Pei
PP
Wang
Jie
J
Yuan
Shi-Ying
SY
Shang
You
Y
Yao
Shang-Long
SL
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D044045:Lipoxins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D016207:Cytokines; D044045:Lipoxins; D009195:Peroxidase