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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte and platelet aggregation stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP) was measured in 32 patients with cerebral ischemia and in 15 controls, using a whole blood aggregometer. The increases in impedance and the reductions in leukocyte and platelet counts were significantly greater in stroke patients than in controls. Aggregation was inhibited by oral ticlopidine, but not by oral aspirin. The effects were clearly counteracted by platelet-activating factor (PAF) antagonists, and counteracted in part by a 5-lipoxygenase inhibitor. The results suggest that platelets tend to be activated by PAF and leukotrienes liberated from hyperaggregable leukocytes in patients with ischemic stroke.
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PMID:Role of platelet-activating factor in aggregation of leukocytes and platelets in cerebral ischemia. 181 11

It has been postulated that lipoxygenase metabolites of arachidonic acid play a role in the pathogenesis of cerebral ischaemia. Severe forebrain ischaemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 min of ischaemia, circulation was restored by removing the arterial clamps and increasing blood pressure to preischaemic levels. During 30 min of cerebral ischaemia, free arachidonic acid increased by approximately 8.5 times compared with the preischaemic level. This accumulation was reversed within 60 min of reperfusion. The concentration of leukotriene C4 in brain tissue increased significantly during reperfusion: treatment with a 5-lipoxygenase inhibitor, AA-861, decreased the increase of brain water content associated with reperfusion. This study demonstrated that the increased arachidonic acid resulting from cerebral ischaemia in rats is metabolized to leukotrienes via the lipoxygenase pathway once circulation is restored, and these leukotrienes may play some role in the development of postischaemic cerebral oedema.
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PMID:Role of brain tissue leukotriene in brain oedema following cerebral ischaemia: effect of a 5-lipoxygenase inhibitor, AA-861. 197 46

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.
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PMID:Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema. 335 24

The 5-lipoxygenase metabolites, leukotrienes, increase in concentration during cerebral ischemia. Azelastine is a new anti-allergic agent which inhibits leukotriene C4 synthesis and release. We examined the neuroprotective properties of azelastine using the hippocampal slice. Azelastine 15 microM significantly protected CA1 evoked responses from hypoxic injury, with CA1 population spike amplitude recovering to a mean 76 +/- 13% in azelastine treated slices, compared to 4 +/- 3% recovery in paired unmedicated slices. The EC50 for this azelastine hypoxic protection was 9.8 microM. Azelastine additionally protected against injury induced by N-methyl-D-aspartate (NMDA), but not non-NMDA glutamate receptor agonists. No hypoxic protection was afforded by diphenhydramine 50 microM, suggesting that azelastine protection did not occur through histamine H1 receptor blockade. The finding of protection with azelastine against hypoxic and NMDA-induced injury suggests that leukotriene production is a common pathway in these forms of neuronal injury, and that leukotriene inhibition may be a useful neuroprotective strategy.
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PMID:Protection from hypoxic and N-methyl-D-aspartate injury with azelastine, a leukotriene inhibitor. 840 89

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid (AA). They constrict blood vessels and enhance vascular permeability inducing vasogenic edema that may hurt the ischemic penumbra after cerebral ischemia and reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most potent inhibitor of 5-lipoxygenase in different tissues. Furthermore, it has considerable inhibitory activity against cyclooxygenase. In this study, after developing a global ischemic model in the rat, the levels of LTC4 and PGE2 in the forebrain were measured, following different reperfusion periods after 10 min ischemia including 8 rats for each reperfused group. Sham operations were performed for each corresponding control group (n = 8). AA metabolites were then correlated with neuropathological findings. In the combined reperfused groups both metabolites increased significantly when compared with 10 min, ischemic group (P < 0.05). In the 8 min reperfused group, PGE2 and LTC4 increased significantly compared with each corresponding control group (P < 0.005). These mediators also increased to high levels compared with the 4 min reperfused group (P < 0.05, P < 0.005). PGE2 and LTC4 were reduced significantly at the 15th and 60th min of reperfusion compared with the 8 min reperfused group (P < 0.05, P < 0.005). NDGA (0.1 mg/kg) reduced both metabolites in the 8 min reperfused group significantly (P < 0.05). Brain cortex specimens were taken for light and electromicroscopical investigations. No significant differences were noted between the structural changes in the 4, 8 and 15 min of reperfusion and NDGA administered groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes. 841 14

This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.
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PMID:Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia. 868 59

Accumulation of arachidonic acid (AA) is greatest in brain regions most sensitive to transient ischemia. Free AA released after ischemia is either: 1) reincorporated into the membrane phospholipids, or 2) oxidized during reperfusion by lipoxygenases and cyclooxygenases, producing leukotrienes (LT), prostaglandins, thromboxanes and oxygen radicals. AA, its metabolite LTC4 and lipid peroxides (generated during AA metabolism) have been implicated in the blood-brain barrier (BBB) dysfunction, edema and neuronal death after ischemia/reperfusion. This report describes the time course of AA release, LTC4 accumulation and association with the physiological outcome during transient cerebral ischemia of gerbils. Significant amount of AA was detected immediately after 10 min ischemia (0 min reperfusion) which returned to sham levels within 30 min reperfusion. A later release of AA occurred after 1 d. LTC4 levels were elevated at 0-6 h and 1 d after ischemia. Increased lipid peroxidation due to AA metabolism was observed between 2-6 h. BBB dysfunction occurred at 6 h. Significant edema developed at 1 and 2 d after ischemia and reached maximum at 3 d. Ischemia resulted in approximately 80% neuronal death in the CA1 hippocampal region. Pretreatment with a 5-lipoxygenase inhibitor, AA861 resulted in significant attenuation of LTC4 levels (Baskaya et al. 1996. J. Neurosurg. 85: 112-116) and CA1 neuronal death. Accumulation of AA and LTC4, together with highly reactive oxygen radicals and lipid peroxides, may alter membrane permeability, resulting in BBB dysfunction, edema and ultimately to neuronal death.
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PMID:Arachidonic acid and leukotriene C4: role in transient cerebral ischemia of gerbils. 1049 17

Prostaglandins and leukotrienes (eicosanoids), metabolites of the arachidonic acid pathway, are subjected to altered synthesis or relocation after an ischemic insult. Although cyclooxygenase (COX) expression has been reported in human cerebral ischemia, no information is available on the expression of 5-lipoxygenase (5-LO) and its topographical correlation to COX induction. The objective of this study was to elucidate the comparative distribution of eicosanoids in ischemic tissues. COX and 5- LO, key enzymes for the synthesis of prostaglandins and leukotrienes, respectively, were examined in autopsied brains. COX1 was expressed intensely in the microglia but weakly in the neurons in control brains. These COX1-immunoreactive microglia showed a more activated form following ischemic damage and hypoxemia. In contrast, COX2 was absent in the control brains, and was induced robustly in the neuronal cell bodies and dendrites during the acute stages of focal ischemic damage, and then subsided at the subacute stages. These COX2-immunoreactive neurons accumulated in the peri-infarct regions, but were absent from the distant regions. In focal ischemic damage and Binswanger's disease, COX2 was up-regulated in the microglia. Neuronal immunostaining for 5-LO was up-regulated occasionally during hypoxemia and focal ischemic damage. Glial cells immunoreactive for 5-LO appeared in the foci of the ischemic damage, with small blood vessels being infiltrated by 5-LO-immunoreactive mononuclear leukocytes. These findings indicate that the isozymes of COX are differentially regulated depending on the cellular source and the types of ischemic damage, and that vascular 5-LO may accelerate the migration of leukocytes and augment the blood-brain barrier permeability. The possibility of increased substrate availability for the other should be noticed in specific inhibition of either COX or 5-LO since these two enzymes are accumulated in parallel in ischemic tissues.
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PMID:A comparative study on the expression of cyclooxygenase and 5-lipoxygenase during cerebral ischemia in humans. 1241 Mar 81

The purpose of this study is to discuss an important component-arachidonic acid (AA) cascade of inflammatory reaction in diabetic rats with cerebral ischemia. Using the model of middle cerebral artery occlusion (MCAO), we have compared the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and measured the levels of their products prostaglandin E2 (PGE(2)) and cysteine-containing leukotrienes (cys-LTs) after different reperfusion periods in diabetic and normal rats. Cerebral ischemia-reperfusion was accompanied by increased expression of COX-2 and release of PGE(2), peaking at 12 h after reperfusion. The expression of COX-2 was maintained at a high level until 24 h after reperfusion, while the levels of PGE(2) were declined rapidly to baseline. The expression of 5-LOX and levels of cys-LTs reached a peak at 6 and 12 h after reperfusion, respectively, and was returned to baseline at 24 h after reperfusion. Compared with normal rats, the expression of COX-2 and 5-LOX as well as release of PGE(2) and cys-LTs was elevated in the brains of diabetic rats, revealing a possible mechanism for hyperglycemia-mediated aggravation of cerebral ischemic injury. A reduction of arachidonic acid metabolites mediated by inhibitors of its metabolites could be helpful in preventing ischemic brain injury in diabetic rats.
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PMID:Metabolic changes of arachidonic acid after cerebral ischemia-reperfusion in diabetic rats. 1476 66

Cerebral ischemia induces 5-lipoxygenase translocation and leukotriene production in the brain. We tried to clarify the pathological significance of 5-lipoxygenase on cerebral ischemia using 5-lipoxygenase knockout mice. No significant difference was observed in the infarct size following permanent and transient ischemia for 60 min between both types of mice. The present study did not support the idea that leukotriene production is involved in infarct expansion in focal cerebral ischemia.
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PMID:Cerebral ischemia in 5-lipoxygenase knockout mice. 1503 36


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