lipoxin-a4-methyl-ester has been researched along with Disease-Models--Animal* in 2 studies
2 other study(ies) available for lipoxin-a4-methyl-ester and Disease-Models--Animal
| Article | Year |
|---|---|
Lipoxin A4 Methyl Ester Reduces Early Brain Injury by Inhibition of the Nuclear Factor Kappa B (NF-κB)-Dependent Matrix Metallopeptidase 9 (MMP-9) Pathway in a Rat Model of Intracerebral Hemorrhage.
BACKGROUND Intracerebral hemorrhage (ICH) is associated with inflammation and disruption of the blood-brain barrier (BBB). Lipoxin A4 methyl ester (LXA4 ME), is a stable synthetic analog of lipoxin with anti-inflammatory properties. This study aimed to investigate the effects of LXA4 ME in a rat model of ICH. MATERIAL AND METHODS Male Sprague-Dawley rats (n=120), between 12-13 weeks of age, were divided into the sham group (sham-operated), the vehicle-treated group (ICH+vehicle), the LXA4 ME-L group (ICH+low-dose LXA4 ME, 10 ng/d), and the LXA4 ME-H group (ICH+high-dose LXA4 ME, 100 ng/d). The ICH model was created by injection of autologous blood into the right basal ganglia. LXA4 ME was injected into the ventricle 10 min after the development of ICH. A modified neurological severity score (mNSS), rotarod latencies, and brain water content were used to evaluate the rats. The TUNEL assay measured neuronal cell death. Western blot was used to measure protein expression of nuclear factor kappa B (NF-kappaB), matrix metalloproteinase-9 (MMP-9), zonula occludens-1 (ZO-1), and claudin-5. RESULTS In the rat model of ICH, treatment with LXA4 ME reduced the levels of proinflammatory cytokines, improved neurologic function, reduced neuronal apoptosis, and reduced cerebral edema associated with damage to the BBB, and reduced the expression levels of NF-kB, MMP-9, ZO-1, and claudin-5. CONCLUSIONS In a rat model of ICH, treatment with LXA4 reduced early brain injury and protected the BBB by inhibiting the NF-kappaB-dependent MMP-9 pathway. Topics: Animals; Apoptosis; Blood-Brain Barrier; Brain; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Cytokines; Disease Models, Animal; Inflammation; Lipoxins; Male; Matrix Metalloproteinase 9; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction | 2019 |
A lipoxin A4 analog ameliorates blood-brain barrier dysfunction and reduces MMP-9 expression in a rat model of focal cerebral ischemia-reperfusion injury.
LXA(4) methyl ester (LXA(4)ME), a lipoxin A(4) analog, reduces ischemic insult in the rat models of transient or permanent cerebral ischemic injury. We investigated whether LXA(4)ME could ameliorate blood-brain barrier (BBB) dysfunction after stroke by reducing matrix metalloproteinase (MMP)-9 expression. Adult male rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Brain infarctions were detected by triphenyltetrazolium chloride (TTC) staining. BBB dysfunction was determined by examining brain edema and Evans Blue extravasation. Temporal expression of MMP-9 was determined by zymography and Western blot. The presence of tissue inhibitors of metalloproteinase-1 (TIMP-1) was also determined by Western blot in tissue protein sample. Brain edema and Evans Blue leakage were significantly reduced after stroke in the LXA(4)ME group and were associated with reduced brain infarct volumes. MMP-9 activity and expression were inhibited by LXA(4)ME after stroke. In addition, LXA(4)ME significantly increased TIMP-1 protein levels. Our results indicate that LXA(4)ME reduces brain injury by improving BBB function in a rat model of MCAO, and that a relationship exists between BBB permeability and MMP-9 expression following ischemic insult. Furthermore, these results suggest that LXA(4)ME-mediated reduction of MMP-9 following stroke are attributed to increased TIMP-1 expression. Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Disease Models, Animal; Lipoxins; Male; Matrix Metalloproteinase 9; Rats; Rats, Sprague-Dawley; Reperfusion Injury | 2012 |