ABSTRACT
Objective To investigate the effects of lipoxin A4 (LXA4) on the inflammatory response to focal cerebral ischemia-reperfusion(I/R) inmy in rats.Methods Fifty-six healthy male SD rats weighing 200-250 g were randomly divided into 3 groups:group Ⅰ sham operation(group S,n=8);group Ⅱ cerebral I/R(n=24)and group Ⅲ lipoxin A4+I/R(group LXA4,n=24).Right mid-cerebral artery was occluded for 2 h by inserting cranially a nylon thread with rounded tip into internal carotid artery.LXA4 0.03 nmol/5 μl was injected into cerebral ventricle at 5 min after cerebral ischemia.Neurological deficit was scored at 24 h of reperfusion.Then four animals in each group were killed and their brains were removed for microscopic examination and expression of MPO at 24 h of reperfusion.Meantime,content of IL-1β,TNF-α,TGF-β1,and IL-10 in the brain tissue were measured at 1,6,12,24 and 48 h of reperfusion by ELISA.Glial cell activity was examined at 24 h of reperfusion by immuno-histochemistry.Results Intra-cerebroventricular administrated LXA4 0.03 nmol/5 μl provided mild neuroprotection against focal cerebral I/R injury,improved neurological deficits,and reduced morphological brain damages and PMN infiltration.LXA4 also decreased the content of TNF-α and IL-1β,and increased the content of IL-10 and TGF-β1.The numbers of activated astroglia and microglia were decreased in group LXA4 compared with group I/R.Conclusion LXA4 protects the brain against I/R injury by inhibiting inflammatory response.
ABSTRACT
Objective To investigate the effect of lipoxin A4 ( LXA4 ) on the permeability of blood-brain barrier (BBB) after focal cerebral ischemia-repeffnsion (I/R) in rats. Methods Fifty-four adult male SD rats weighing 200-250 g were randomly divided into 3 groups ( n = 18 each): group Ⅰ sham operation (group S); group Ⅱ focal cerebral I/R ( group I/R) and group Ⅲ LXA4 ( group L). Focal cerebral I/R was produced by middle cerebral artery occlusion (MCAO) with a 4-0 nylon thread with rounded tip inserted into right internal jugular vein and threaded cranially in group Ⅱ and Ⅲ . In group Ⅲ LXA4 100 ng was injected into right lateral ventricle of the brain after MCA was successfully occluded. MCAO was maintained for 2 h. The neurological deficit was evaluated and scored (0 = no deficit, 5 = death) at 24 h of reperfusion. 2% Evans blue 4 ml/kg was injected via femoral vein at 1 h before the animals were sacrificed. The animals were killed and their brains were immediately removed for determination of brain water content, Evans blue content and expression of matrix metalloproteinase-9 (MMP-9)in the ischemic cortex. Results The neurologic deficit scores, the brain water and Evans blue content and MMP-9 protein expression in the cortex were significantly higher in I/R group than in S group. The cerebral I/R-induced changes were significantly attenuated in LXA4 group. Conclusion LXA4 can protect blood-brain barrier against cerebral I/R injury by inhibiting MMP-9 protein expression in the brain tissue.
ABSTRACT
Objective To investigate the effect of lipoxin A4(LXA4) on inflammatory response in a rat model of permanent focal cerebral ischemia (PFCI). Methods Seventy-two adult male SD rats weighing 200-250 g were randomly divided into 3 groups (n = 24 each):group Ⅰ sham operation (group S); group Ⅱ PFCI and group Ⅲ LXA4. PFCI was induced by thread occlusion of right middle cerebral artery according to the method described by Longa in group Ⅱ and Ⅲ. In group Ⅲ LXA4 100 ng/5 μl was injected into right ventricle of the brain after PFCI was successfully induced, while in group Ⅰ and Ⅱ equal volume of normal saline was injected instead of LXA4. Six animals were killed at 6, 12 and 24 h of ischemia. Their brains were immediately removed for microscopic examination and determination of myeloperoxidase (MPO) activity, TNF-α, IL-10 and transforming growth factor-β1 (TGF-β1) contents in the ischemic cortex. The expression of glial fibrillary acidic protein (GFAP)was measured by immuno-histochemistry. Apoptosis in neurons was assessed using TUNEL. Results PFCI significantly increased MPO activity, TNF-α, IL-10 and TGF-β1 contents and GFAP expression in the ischemic cortex and neuronal apoptosis in group Ⅱ as compared with group S. LXA4 significanfly decreased MPO activity,TNF-α content, GFAP expression and neuronal apoptosis and increased IL-10, TGF-β1 contents at 12,24 h of ischemia. LXA4 significantly ameliorated PFCI-induced cerebral histopathologic damage. Conclusion LXA4 can protect the brain against PFCI injury by inhibiting inflammatory response.
ABSTRACT
Aim To investigate the protective effect of lipoxin A4(LXA4)on ischemic brain injury in a rat model of permanent focal cerebral ischemia.Methods Adult male Sprague-Dawley rats weighing 200～250 g were used and rats were randomly divided into four groups:sham group,ischemia alone group,LXA4 10 ng group and LXA4 100 ng group.Permanent focal cerebral ischemia was induced by improved thread occlusion of right middle cerebral artery.Approximately 10 mm of nylon surgical thread was inserted into the right internal carotid artery in the rats of sham group.After the middle cerebral artery occlusion,the same volume of LXA4(5 ?l)or isotonic Na chloride(5 ?l)was injected respectively into the right lateral ventricle of the rat in 10 minutes.After 24 h of ischemia,the neurological deficit and the infarct volume were assessed by the method of Longa's score and 2,3,5-triphenyltetrazolium chloride(TTC)staining;the levels of malondialdehyde(MDA)and actvities of myeloperoxidase(MPO)in the ischemia cortex were measured by spectrophotometer;the contents of tumor necrosis factor-?(TNF-?)and interleukin-1?(IL-1?)were assayed by ELISA method.The histopathological change was observed after HE staining.Results Treatment with LXA4 10 ng or 100 ng significantly improved functional recovery,reduced relative infarction volume,inhibited MPO activity,decreased MDA,TNF-? and IL-1? levels,and improved histopathological injury.Moreover,the effects of neurological recovery and decreasing TNF-? level in LXA4 100 ng group were better than those in 10 ng group.Conclusion Treatment with LXA4 protects against permanent focal cerebral ischemia injury in rats.