6-ketoprostaglandin-f1-alpha and Brain-Ischemia

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Brain Ischemia; Dinoprostone; Eicosanoids; Fetal Diseases; Fetus; Rats; Thromboxane B2; Tritium

To observe the therapeutic effects of midnight-noon ebb-flow method of selecting acupoints (MNEFMSA) for acute ischemic cerebrovascular diseases (AICD) and its influence on hemorrheology and on the levels of interleukin-6 (IL-6), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha).. The 90 cases were randomly divided into 3 groups, each consisting of 30 cases. The drug group was treated mainly by routine medication; in addition to medication, the affected-channel group was treated by acupuncture at points along the course of the affected channel, and the MNEFMSA group was treated by MNEFMSA.. The total effective rate of MNEFMSA group, affected-channel group and drug group was 96.67%, 90% and 73.33% respectively. The total effective rate of MNEFMSA group was obviously superior to that of the drug group (P < 0.01), and cure rate and marked improvement rate were obviously superior to those of the drug group and the affected-channel group (P < 0.05 or P < 0.01). After treatment, the three groups all got improvements in the hemorheological indexes, of which MNEFMSA group got marked improvements in the whole blood viscosity and erythrocyte deformability rate, significantly different from the other two groups (P < 0.05). At the early stage of treatment and after treatment, the three groups all had IL-6, TXB2 and 6-keto-PGF1alpha obviously improved (P < 0.05 or P < 0.01), of which MNEFMSA group got obvious improvement in 6-keto-PGF1alpha and IL-6 ever since the early stage of the treatment (P < 0.05).. In the treatment of acute ischemic cerebrovascular diseases, MNEFMSA can markedly raise the clinical therapeutic effects by improving the hemorheological indexes, lowering the level of IL-6, and restoring the dynamic equilibrium between TXB2 and6-keto-PGF1alpha, so as to promote the recovery of cerebral nervous function.

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Points; Acupuncture Therapy; Adult; Aged; Aged, 80 and over; Brain Ischemia; Female; Humans; Interleukin-6; Male; Medicine, Chinese Traditional; Middle Aged; Thromboxane B2

To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke.. Randomized clinical trial of three graded dose levels.. A geriatric clinic attached to a nursing home.. Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks.. Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha.. Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings.. We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Brain Ischemia; Bridged Bicyclo Compounds; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Humans; Nicotinic Acids; Platelet Aggregation Inhibitors; Thromboxane B2

Arachidonic acid (AA) and its vasoactive metabolites have been implicated in the pathogenesis of brain damage induced by cerebral ischemia. The membrane AA concentrations can be reduced by changes in dietary fatty acid intake. The purpose of the present study was to investigate the effects of chronic ethyl docosahexaenoate (E-DHA) administration on the generation of eicosanoids of AA metabolism during the period of reperfusion after ischemia in gerbils. Weanling male gerbils were orally pretreated with either E-DHA (100, 200 mg/kg) or vehicle, once a day, for 10 weeks, and subjected to transient forebrain ischemia by bilateral common carotid occlusion for 10 min. E-DHA (200 mg/kg) pretreatment significantly decreased the content of brain lipid AA at the termination of treatment, prevented postischemic impaired regional cerebral blood flow (rCBF) and reduced the levels of brain prostaglandin (PG) PGF(2alpha) and 6-keto-PGF(1alpha), and thromboxane B(2) (TXB(2)), as well as leukotriene (LT) LTB(4) and LTC(4) at 30 and 60 min of reperfusion compared with the vehicle, which was well associated with the attenuated cerebral edema in the E-DHA-treated brain after 48 h of reperfusion. These data suggest that the E-DHA (200 mg/kg) pretreatment reduces the postischemic eicosanoid productions, which may be due to its reduction of the brain lipid AA content.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Brain; Brain Chemistry; Brain Edema; Brain Ischemia; Cerebrovascular Circulation; Dinoprost; Docosahexaenoic Acids; Eicosanoids; Fatty Acids; Gerbillinae; Leukotriene B4; Leukotriene C4; Lipids; Male; Reperfusion; Thromboxane B2

The plasma expression levels of ET-1, TXB2, 6-keto-PGF1alpha, vWF at different time after cerebral ischemia were assayed for observing the effects of baicalin, jasminoidin, cholalic acid, hydrolysis fluid of nacre and the combined prescription (CP) on cerebral vasoconstriction and endothelial cells in MCAO rats.. The plasma levels of ET-1, TXB2, 6-keto-PGF1alpha in MCAO rats were detected by the method of RIA and the plasma expressions of vWF were observed by ELISA.. The levels of ET-1, TXB2/6-keto-PGF1alpha and vWF all increased at different time after cerebral ischemia, so do TXB2 at 12 hours after ischemia. The expression of 6-keto-PGF1alpha significantly reduced at different time point after ischemia in MCAO rat. There were no significant changes after medicine treating 12 hours except baicalin's increasing 6-keto-PGF1alpha level. Jasminoidin and CP significantly reduced the expression of ET-1 at 24 hours after ischemia, so do all effective components except CP on expression of TXB2 at 12 hours after ischemia. The expression of TXB2 was significantly decreased by baicalin and CP at 24 hours after cerebral ischemia. Both baicalin and cholalic acid significantly increased the expression of 6-keto-PGF1alpha at 12 hours after ischemia while cholalic acid and hydrolysis fluid of nacre increased its level after ischemia for 24 hours. TXB2/6-keto-PGF1alpha ratio was reduced distinctively by baicalin, jasminoidin, cholalic acid, CP at the point of 12 hours, while decreased by baicalin and CP, and increased by jasmionoidin at the point of 24 hours. On the other hand, baicalin, hydrolysis fluid of nacre significantly reduced and jasminoidin increased the expression of vWF at the point of 12 hours. At the point of 24 hours, expression of vWF reduced by hydrolysis fluid of nacre and increased by baicalin.. The higher plasma expression of ET-1, TXA2 in plasma aggravated cerebral vasoconstriction and damaged endothelial cells. At the same time, the effective components of "Qing Kai Ling" inhibit the expression of ET-1 , TXA2 and reduce both TXB2/6-keto-PGF1alpha ratio and level of vWF. As a result, they relax cerebral microvessel and protect endothelial cells by different pathway at different target points.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Ischemia; Cholic Acid; Drugs, Chinese Herbal; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Flavanones; Male; Rats; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; von Willebrand Factor

The cerebral ischemia rabbit model was made by using the occlusion of four vessels. The results showed that TXB2 and cAMP contents in brain tissues and the latter in plasma markedly increased (P < 0.05, P < 0.01), the 6-keto-PGF1 alpha in brain tissues significantly lowered (P < 0.05) in ischemia formed 30 minutes and 45 minutes after reperfusion. After intravenous injection of Astragalus membranaceus (AM) extracts (3.3 g/kg), Huoxuefang (HXFO and Yiqi Houxue Fang (YQHXF) consisted of AM and HXF before ischemia, the marked increase of TXB2 contents after reperfusion was inhibited (P < 0.05) and the 6-keto-PGF1 alpha in brain tissues after reperfusion were increased (P < 0.01) in HXF and YQHXF group, which change the AM extracts didn't have (P < 0.05). HXF could markedly inhibit the increase of cAMP in brain tissues after reperfusion P < 0.05), while the AM extracts and YQHXF couldn't (P > 0.05). All above-mentioned suggested that the above-mentioned suggested that the balance disorder of TXA2/PGI2 in brain tissues might participate in the occurrence of cerebral reperfusion injury and YQHXF might act against this injury by means of improving the balance of TXA2/PGI2 in brain tissues, which was mainly released by HX drugs of it.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Astragalus propinquus; Brain; Brain Ischemia; Cyclic AMP; Drugs, Chinese Herbal; Female; Male; Rabbits; Reperfusion Injury; Thromboxane B2

Berberine (Ber) 20 mg.kg-1.d-1 for 1, 3, or 5 d inhibited platelet aggregation induced by ADP, arachidonic acid (AA) and collagen (Coll) in rats with 24 h reversible middle cerebral artery occlusion (MCAO), and the platelet adhesiveness was inhibited as well. Using radioimmunoassay method, the thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) contents in rat plasma were measured 24 h after MCAO. The results indicate that the TXB2 levels after drug treatment were lower than those in ischemia control rats, but the 6-keto-PGF1 alpha levels showed no obvious difference between the two groups. The same dose of Ber was also shown to inhibit thrombosis formation. This suggests that the decline of platelet aggregation and decrease of TXB2 content may be one of the important factors involved in the anti-cerebral ischemia effect of Ber.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Berberine; Brain Ischemia; Male; Platelet Adhesiveness; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Thromboxane B2

In this study Mongolian gerbils were submitted to a normothermic bilateral carotid ligation lasting 5 min. A noncompetitive antagonist of NMDA receptors, MK-801, 0.8 mg/kg, was injected i.p. 30 min before ischemia, or the ganglioside GM1, 30 mg/kg, was given i.p. for 3 days, twice a day. The morphology of the hippocampal CA1 neurones and the brain content of cyclooxygenase metabolites of arachidonic acid: prostaglandin 6-keto PGF1 alpha and thromboxane Tx B2 were studied. Untreated ischemia induced the accumulation in brain of the 6-keto PGF1 alpha and Tx B2 immunoreactive materials, and resulted in a lesion of 70% of CA1 neurones. In the MK-801- and GM1-pretreated groups the postischemic levels of Tx B2 were significantly decreased. However MK-801 and GM1 did not prevent damage to the CA1 neurones in gerbils normothermic after ischemia, whereas a partial neuroprotection was observed in hypothermic, MK-801 treated gerbils. The results of this study indicate that NMDA receptors may participate in the mechanism of postischemic release of eicosanoids in brain. They also confirm a potential modulatory role of gangliosides. These results are discussed in terms of the involvement of cyclooxygenase metabolites of arachidonic acid in the mechanism of a selective delayed neuronal damage to the hippocampus CA1 after ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Ischemia; Dizocilpine Maleate; Female; G(M1) Ganglioside; Gerbillinae; Hippocampus; Male; Prostaglandins; Thromboxane B2

The effect of mild and moderate hypothermia on ischemia-induced glutamate release and eicosanoid production was evaluated in WKY rats subjected to incomplete forebrain ischemia. Under isoflurane anesthesia, microdialysis probes were inserted into the hippocampus and caudate nucleus. In four groups of rats, the intraischemic temperature was maintained at either 38 degrees C (normothermia), 36 degrees C, 34 degrees C (mild hypothermia) and 30 degrees C (moderate hypothermia). In these groups, normothermia was restored immediately upon reperfusion. In two additional groups, both intra- and post-ischemic temperatures were maintained at either 34 degrees C or 30 degrees C. The levels of glutamate were measured in the dialysate collected during ischemia and the levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha were measured in dialysate collected prior to and after ischemia. As expected, hypothermia reduced ischemia-induced glutamate release in both structures. However, the application of mild hypothermia did not attenuate post-ischemic levels of all eicosanoids measured. Moderate hypothermia (30 degrees C) attenuated the post-ischemic increase in the levels of PGF2 alpha. The data suggest that the processes that lead to eicosanoid formation are less sensitive to temperature reduction than those that lead to glutamate release.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Temperature; Brain Chemistry; Brain Ischemia; Caudate Nucleus; Dinoprost; Eicosanoids; Glutamic Acid; Hippocampus; Hypothermia; Microdialysis; Rats; Rats, Inbred WKY; Reperfusion; Thromboxane B2

Hippocampal slices of rats at postnatal day 7 were submitted to superfusion with Ca(2+)- and Mg(2+)-free, bicarbonate buffered ion balanced medium, and perfusate concentrations of eicosanoids: thromboxane B2 and 6-keto prostaglandin F1 alpha were determined by the radioimmunoassay. It was noted that the permanent presence of Ca2+ increased the basal eicosanoid level, and in these conditions modulation of eicosanoid production was lost, whereas temporary, a 20 min application of 1.3 mM Ca2+ did not influence significantly eicosanoid release. A 20 min application of the anoxic/aglycemic medium containing calcium did not change the content of eicosanoids in superfusates. A significant stimulation of the thromboxane B2 and 6-keto prostaglandin F1 alpha release was noted provided the application of the experimental medium was accompanied by a 10 min arrest of superfusion. This effect was inhibited by MK-801 and quinacrine, suggesting an involvement of NMDA receptors and phospholipase A2. We propose that a model of anoxic/aglycemic superfusion with a stop flow period allows retention of endogenous glutamate in the extracellular fluid, resembling a similar effect during in vivo ischemia, whereas during a continuous superfusion glutamate is immediately washed out. Consequently, an application of the anoxic/aglycemic medium accompanied by a temporary arrest of superfusion represents more adequate in vitro model of ischemia than a constant superfusion with this medium. In these conditions NMDA receptors mediate eicosanoid release.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Brain Ischemia; Calcium; Culture Techniques; Dizocilpine Maleate; Eicosanoids; Hippocampus; Hypoxia; N-Methylaspartate; Quinacrine; Radioimmunoassay; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Thromboxane B2

The products resulting from arachidonic acid metabolism of the both cyclo-oxygenase and lipoxygenase pathways possess strong physiological activities, such as vasoconstriction and the enhancement of vascular permeability. Therefore, it is likely that these metabolites are involved in cerebral circulatory disturbance and the formation of brain edema in cerebral ischemia. It is reported that intracerebral injection of leukotriene B4, C4, and E4 increased blood-brain barrier permeability. Thus, it is suggested that leukotrienes may induce vasogenic cerebral edema. We examined role of the products resulting from arachidonic acid of the cyclo-oxygenase and lipoxygenase pathways on the formation of ischemic cerebral edema in rats with focal cerebral ischemia. Focal cerebral ischemia was induced by the occlusion of right middle cerebral artery. Acyclo-oxygenase inhibitor, indomethacin (4mg/kg), was given intravenously 30 minutes before the occlusion of the middle cerebral artery. Also, azerastine hydrochloride (8mg/kg), which has an inhibitory effect on the production and release of leukotrienes from human neutrophil as well as an antagonistic action on leukotrienes and another inhibitory effect on the production of superoxide anion, was given intravenously 5 minutes prior to occlusion. Concentrations of prostaglandin E2 (PGE2), thromboxane B2 (TxB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and leukotriene C4 (LTC4) measured by radioimmunoassay. The percent water content of a cerebral hemisphere was determined by the wet-dry weight method. In the occluded hemisphere, PGE2, 6-keto-PGF1 alpha, TxB2 and LTC4 significantly increased at 2, 6, 12 hours respectively, following the MCA occlusion as compared to the control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Brain Edema; Brain Ischemia; Cerebral Arteries; Constriction; Dinoprostone; Leukotriene C4; Male; Rats; Rats, Wistar; Thromboxane B2

Policosanol is a mixture of higher primary aliphatic alcohols, isolated from sugar cane wax, whose main component is octacosanol. Policosanol (25, 50 and 200 mg/kg) administered by the oral route not only significantly reduced serum thromboxane B2 (TXB2) levels but also, at 200 mg/kg significantly increased 6-keto-PGF1 alpha in Mongolian gerbils. Policosanol at 200 mg/kg significantly protected against cerebral ischemia induced by unilateral ligation of common carotid artery in Mongolian gerbils. In this experimental model, combined administration of ineffective doses of policosanol (25 mg/kg) and aspirin (ASA) (30 mg/kg) significantly protected animals indicating a synergism between them.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Brain Ischemia; Drug Synergism; Epoprostenol; Fatty Alcohols; Gerbillinae; Thromboxane A2; Thromboxane B2

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibu

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Weight; Brain Ischemia; Caudate Nucleus; Cell Death; Dialysis; Dinoprost; Eicosanoids; Hippocampus; Ibuprofen; Neurons; Prosencephalon; Rats; Rats, Inbred WKY; Stereotaxic Techniques

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Brain Ischemia; Catalase; Cerebrovascular Circulation; Free Radical Scavengers; Hypercapnia; Hypotension; Isoproterenol; Superoxide Dismutase; Superoxides; Swine; Vasodilation

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Arterioles; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Dinoprostone; Female; Hypercapnia; Hypotension; Isoproterenol; Male; Swine; Transforming Growth Factor beta; Vasodilation

By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Chemistry; Brain Ischemia; Cerebrovascular Disorders; Epoprostenol; Female; Radioimmunoassay; Rats; Rats, Wistar; Resuscitation

Thirty three New Zealand rabbits were randomly divided into three groups, i.e. the control group, the high atmospheric pressure. (HAP) group and the hyperbaric oxygenation (HBO) group. The experimental animals were made into the models of reperfusion for acute incomplete cerebral ischemia. The blood-gas analyses drawn from the common carotid arteries and the internal jugular veins were carried out, and the 6-keto-PGF1a and TXB2 in the brain tissues determined. The results showed that the contents of 6-keto-PGF1a in the brain tissues of the HBO groups were significantly increased (P less than 0.01). While those of TXB2 were significantly decreased (P less than 0.01). The po2 in both the arterial and the venous blood were obviously elevated in the HBO group. Pathological examination showed that the brain tissue damages in the HBO group were the slightest among the three groups. It was postulated that the effect of HBO on 6-keto-PGF1a and TXB2 might reflect one of the mechanisms of HBO for the treatment of acute cerebral ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Gas Analysis; Brain Ischemia; Hyperbaric Oxygenation; Rabbits; Reperfusion Injury; Thromboxane B2

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1 alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1 alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1 alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1 alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1 alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1 alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB2 and 6-keto-PGF1 alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Ischemia; Caudate Nucleus; Dialysis; Hippocampus; Rats; Thromboxane B2

By occluding the bilateral carotid arteries of rabbits to produce bilateral partial cerebral ischemia, and by using RIA and ELISA to measure the levels of Beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in plasma, the authors found that the levels of beta-TG, PF4 and TXB2 in plasma had significantly increased (P less than 0.01), but the level of 6-keto-PGF1 alpha in plasma showed no change (P greater than 0.05) after cerebral ischemia appeared. The results of the Ligusticum wallichii (Ligusticum) pre-treatment to the test-group showed that the levels of beta-TG, PF4 and TXB2 in plasma had significantly decreased (P less than 0.01), and the level of 6-keto-PGF1 alpha in plasma had significantly increased (P less than 0.05). This suggested that the Ligusticum treatment could effectively inhibit the platelet activation in vivo and correct the TXA2-PGI2 imbalance in blood after cerebral ischemia. In this study, some new approaches were explored to explain the mechanisms of Ligusticum for preventing and treating cerebral ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; beta-Thromboglobulin; Brain Ischemia; Drugs, Chinese Herbal; Female; Male; Platelet Factor 4; Rabbits; Thromboxane B2

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Aspirin; beta-Thromboglobulin; Blood Platelets; Brain Ischemia; Cell Survival; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Ticlopidine

Reperfusion of ischemic brain is associated with production of thromboxane A2 (TXA2), a proaggregatory vasoconstrictor. We used an animal model of transient forebrain ischemia to study the effects of 1-benzylimidazole (1-BI), a selective inhibitor of thromboxane synthase, upon cerebral eicosanoid levels and cerebral blood flow. Male Wistar rats were subjected to 30 minutes of four-vessel occlusion. The mean +/- SEM brain level of TXB2, the stable metabolite of TXA2, determined after 60 minutes of reperfusion was 101 +/- 20 pg/mg brain protein in five ischemic control rats. Infusion of 10 micrograms/g 1-BI reduced mean +/- SEM cerebral TXB2 concentration to 11 +/- 3 pg/mg brain protein in five rats (p less than or equal to 0.002). Mean +/- SEM hemispheric cerebral blood flow measured in four ischemic control rats after 60 minutes of reperfusion was 42 +/- 9 ml/100 g brain/min compared with 104 +/- 13 ml/100 g brain/min in three 1-BI-treated rats (p less than or equal to 0.001). Mean +/- SEM hippocampal blood flow in four ischemic control rats after 60 minutes of reperfusion was 51 +/- 14 ml/100 g brain/min compared with 125 +/- 25 ml/100 g brain/min in three 1-BI-treated rats (p less than or equal to 0.04). We conclude that selective inhibition of thromboxane synthase may alleviate ischemic brain damage by reducing cerebral TXA2 concentrations and elevating cerebral blood flow.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Brain Ischemia; Cerebrovascular Circulation; Eicosanoic Acids; Male; Rats; Rats, Inbred Strains; Thromboxane B2; Thromboxane-A Synthase

We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Ischemia; Cats; Cerebral Arteries; Cerebrovascular Circulation; Constriction; Dinoprost; Dinoprostone; Female; Male; Thromboxane B2

Effects of ischemia (20 min) on cerebral cortical prostanoid synthesis and microvascular responses to hypercapnia and topical acetylcholine were examined in anesthetized newborn pigs. Pial arteriolar dilation in response to hypercapnia (10% CO2 ventilation, 10 min) was absent 2 h after ischemia and reversed toward constriction by 24 h postischemia. In sham control piglets, hypercapnia increased cortical periarachnoid fluid prostanoid concentrations. After ischemia, hypercapnia did not affect prostanoid concentrations on the brain surface. Acetylcholine (10(-3) M)-induced pial arteriolar constriction was reversed toward dilation 24 h after cerebral ischemia. Further, acetylcholine-induced prostanoid synthesis was markedly attenuated after ischemia. We conclude that cerebral ischemia-reperfusion alters cerebral prostanoid synthesis and microvascular control in newborn pigs. These abnormalities persist for at least 24 h.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Animals; Animals, Newborn; Brain; Brain Ischemia; Cerebrovascular Circulation; Dinoprost; Dinoprostone; Hypercapnia; Prostaglandins; Swine; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Ischemia; Glucose; Insulin; Lactates; Lactic Acid; Male; Rats; Rats, Inbred WKY

The time-dependent release of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane (Tx) B2, and 6-keto-PGF1 alpha (6-keto) from brain was measured before, during, and after a 15-min interval of total ischemia (four-vessel occlusion) in halothane-anesthetized cats using the technique of cerebroventricular perfusion. Resting levels of PGE2, PGF2 alpha, 6-keto, and Tx were: 253 +/- 75, 953 +/- 300, 650 +/- 200, and 550 +/- 170 pg/ml, respectively. During the 15-min ischemia, all prostanoids rose significantly, yet the highest levels were not observed until the first 15-60 min of the reflow at which time levels of PGE2, PGF2 alpha, 6-keto, and Tx, as compared with the preischemic baseline, rose approximately 8, 3.4, 3, and 55-fold, respectively. Significantly, although all prostanoids showed increases relative to baseline, the ratios of PGF2 alpha/6-keto and PGE2/6-keto remained stable throughout the experiment in both groups of animals. In contrast, the Tx/6-keto ratio rose from approximately 1 to approximately 30 during the 60 min after reflow in untreated cats. Treatment with zomepirac sodium (5 mg/kg, i.v.), a cyclooxygenase inhibitor, resulted in highly significant reductions in the levels of all prostanoids during the preischemic period. In zomepirac sodium-treated animals, there were also highly significant reductions in the prostanoid response to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Ischemia; Cats; Dinoprost; Dinoprostone; Extracellular Space; Female; Fibrinolytic Agents; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thromboxane B2; Tolmetin

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Brain; Brain Ischemia; Cell Membrane Permeability; G(M1) Ganglioside; Lactates; Male; Rats; Rats, Inbred Strains; Reperfusion; Thromboxane B2

We found recently that exogenously administered PGD2, PGE1 and PGI2 showed a protective effect against cerebral hypoxia/ischemia in mice. In the present study, to find out whether these PGs play a pathophysiological role in cerebral hypoxia/ischemia, we examined a possible role of PGs in the development of adaptive protection against cerebral hypoxia/ischemia. Mice were pretreated with a sublethal dose of KCN, hypoxic gas mixture and electroshock 10-120 min before tests. Ten to thirty min after pretreatment with a sublethal dose of KCN, mice proved to be significantly protected against cerebral hypoxia/anoxia in all models studied: KCN-induced anoxia, normobaric hypoxia and decapitation-induced gasping. Similar results were observed when hypoxic gas and electroshock were used as pretreatments. These facts indicate that the protective effect does not depend on how cerebral hypoxia/anoxia is induced but on the substances formed in the brain after hypoxia/anoxia as well as electroshock. Brain concentrations of cyclooxygenase products markedly increased subsequent to hypoxia/anoxia as well as electroshock. The increase in PGs formation as well as resistance to hypoxia was prevented by pretreatment with indomethacin. These findings suggest that endogenously formed PGs at least including the three PGs, PGD2, PGE1 and prostacyclin in mouse brain during or after hypoxia/ischemia are responsible for the increase of resistance to hypoxia/ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Adaptation, Physiological; Animals; Brain; Brain Ischemia; Electroshock; Hypoxia, Brain; Indomethacin; Male; Mice; Nitrogen; Potassium Cyanide; Prostaglandins; Thromboxane B2

The aim of this study was to observe whether acetylsalicylic acid (ASA) had different effects in both sexes. Out of the ischemic stroke patients who were admitted to the National Taiwan University Hospital (NTUH), those who had not taken ASA or ASA-like drugs for more than 2 weeks were selected for this study. For the diagnosis of ischemic stroke, computed tomography (CT) of the brain was performed in all cases, and for differential diagnosis, other necessary procedures were employed in a few cases. The serum salicylate (SA) level was measured by Trinder's method, thromboxane B2 (TXB2) and 6-keto-PGF1 alpha by radioimmunoassay, threshold concentration of adenosine diphosphate (ADP) by Born's method, and circulating platelet aggregates (CPA) by Wu and Hoak's method. The present study showed that the means of serum SA levels after administration of the same dose of ASA were not significantly different between the two sexes. After ingestion of ASA, a single dose of 75 mg, 300 mg or 600 mg, or 300 mg 4 times a day, mean plasma TXB2 levels were significantly suppressed and mean threshold concentrations of ADP were significantly elevated in the two sexes. After administration of above-mentioned various doses of ASA, the abnormally high plasma TXB2 levels and abnormally low threshold concentrations of ADP and CPA ratios were significantly normalized in both male and female patients. Plasma 6-keto-PGF1 alpha levels were not influenced by ingestion of ASA 75 mg, but significantly depressed by administration of ASA 300 mg in both sexes. There were no sex differences in the antiplatelet effect of ASA in this experiment.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Aged; Aspirin; Blood Platelets; Brain Ischemia; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Platelet Aggregation; Salicylates; Salicylic Acid; Sex Factors; Thromboxane B2

This study examined the changes in cerebral blood flow, water content, and lipoxygenase metabolites (leukotrienes) following bilateral carotid artery occlusion (BCO) and reperfusion in the gerbil. The effect of inhibiting lipoxygenase with nordihydroguaretic acid (NDGA) was also examined. BCO caused cerebral blood flow (measured using H2 clearance) to decline from 23.5 +/- 1.9 to 4.5 +/- 1.9 ml/min/100 gm. Reperfusion increased flow to 27.9 +/- 4 ml/min/100 gm at 10 min, which declined to 13.7 +/- 1.3 ml/min/100 gm at 50 min. Concomitant oedema measurement revealed brain specific gravity decreasing to 1.0402 +/- 0.0014 at 10 min and to 1.0325 +/- 0.0006 at 50 min reperfusion (nonoccluded controls). Leukotriene B4 (LTB4) increased from 26.8 +/- 4.6 to 33.5 +/- 2.1 pg/mg protein 10 min after reperfusion (p less than 0.05), but declined to 21.8 +/- pg/mg protein by 100 min (vs nonischaemic control = 21.3 +/- 2.9 pg/mg protein). Activation of arachidonate metabolism was confirmed by significantly increased 6 keto PGF1 alpha. Pretreatment of the animals with NDGA did not alter CBF, but increased specific gravity above saline-treated controls at 50 min of reperfusion (NDGA = 1.0370 +/- 0.002 vs control = 1.0325 +/- 0.0006, p less than 0.05). Similarly, NDGA blunted the increase in LTB4 formation 10 min after reperfusion (control = 26.8 +/- 4.6 pg/mg protein vs NDGA = 29.7 +/- 2.9 pg/mg protein, p = N.S.). These findings indicate that LTB4 production is stimulated by BCO and reperfusion in the gerbil, and that this stimulation occurs early on in the reperfusion. Further, we observe that the lipoxygenase inhibitor NDGA limits the formation of ischaemic cerebral oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Brain Chemistry; Brain Edema; Brain Ischemia; Gerbillinae; Leukotriene B4; Lipoxygenase; Regional Blood Flow

A thrombo-embolic stroke model was produced by the internal carotid artery (ICA) infusion of arachidonic acid (AA). The differences in responses to AA ICA infusion were investigated in stroke-resistant spontaneously hypertensive rats (SHRSR) and Wistar-Kyoto (WKY) rats. The SHRSR showed a higher mortality, more severe brain oedema and brain metabolic impairment, more prominent elevation of TXB2 and 6-keto-PGF1 alpha. Electron microscopic observation revealed more severe endothelial damage, mitochondrial swelling and perivascular oedema and earlier thrombus formation in SHRSR than in WKY rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Brain; Brain Ischemia; Cerebrovascular Disorders; Hypertension; Male; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Thromboxane B2

Three different levels of global forebrain ischemia were induced in rats and their plasma levels of Thromboxane B2 (TXB2) and 6 Keto PGF1 alpha were determined to investigate the relation between severity of ischemia and eicosanoid production. Ischemia stimulates the activity of cellular lipase whose actions cause deacylation of brain phospholipids and release of free fatty acids. Arachidonic acid (A.A.) is one of the predominant fatty acids which is liberated in brain after ischemia. A.A. is the primary substrate for the synthesis of prostaglandins (PGs), Thromboxane A2 (TXA2) and Prostacyclin (PGI2), which play an important role in regulation of platelet aggregation and vasotonus. Thromboxane is a potent platelet aggregator and vasoconstrictor. On the other hand, PGI2 has the opposite nature. Therefore it can be considered that PGs and moreover, the balance of TXA2 and PGI2 may have an intimate relation to the development of cerebral ischemia. Three different levels of ischemia were produced by bilateral carotid artery ligation (BLCL) using three kinds of rats with different blood pressure ranges, namely, SHRSP (Stroke-prone spontaneously hypertensive rats), SHRSR (Stroke-resistant spontaneously hypertensive rats) and WKY (Wistar kyoto rats). It is known that higher pressure groups suffer severe ischemia by BLCL procedure. Hypertensive rats (SHRSP, SHRSR) were originally produced from WKY. The experimental animals used were about 300 gr and 16 weeks old male rats. The plasma and brain TXB2 and 6 Keto-PGF1 alpha, stable metabolites of TXA2 and PGI2 were measured by radioimmunoassay. The chronological changes of brain and plasma PGs levels after ischemia using SHRSR were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Body Water; Brain Chemistry; Brain Ischemia; Carotid Arteries; Cerebrovascular Circulation; Epoprostenol; Hypertension; Ligation; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2

Thromboxane A2 and prostacyclin are two compounds which have been implicated as important modulators of local cerebral blood flow. Concentrations of the stable metabolites of these two compounds, thromboxane B2 and 6-keto-PGF1 alpha, were measured in cerebrospinal fluid (CSF) from eight acute ischaemic stroke patients and 14 patients with no evidence of cerebrovascular disease. Concentrations of thromboxane B2 ranged from 0.15 to 4.0 pg/ml and were significantly higher (P = 0.025) in the ischaemic stroke group when compared with the control group (0.1-0.3 pg/ml). Simultaneously acquired concentrations of 6-keto-PGF1 alpha were not elevated in the stroke group when compared to normals. These clinical findings support evidence from animal studies that emphasizes the importance of cerebral prostaglandins in mediating the secondary vascular changes of cerebral infarction. In conclusion there is an aberration in CSF thromboxane B2 concentrations in patients who have had a stroke. This may be an acute or chronic phenomenon.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Brain Ischemia; Humans; Middle Aged; Thromboxane B2

Vascular eicosanoids (E) thromboxane (measured as T X B2) and prostacyclin (measured as 6-keto-PGF1 alpha) may modulate hemodynamic parameters in brain circulation. We have studied (a) the effects of the administration of vasoactive drugs, in the rat, on T X B2 and 6-keto-PGF1 alpha levels and release in brain cortex, and (b) changes of brain vascular E levels during hypoxia and recovery, in the same animal species. Administration of vasoactive drugs (papaverine, dipyridamole, the carbochromene derivative AD6 and nifedipine) to rats resulted in differential effects on endogenous levels and post-decapitation release of both compounds. Reduction of the T X B2/6-keto-PGF1 alpha balance in brain cortex was obtained with papaverine and AD6, whereas nifedipine reduced 6-keto-PGF1 alpha more than T X B2. During hypoxia there was no significant modification of brain vascular E, but during recovery both compounds were decreased. Thus pharmacological treatments during recovery from hypoxia may normalize brain vascular E levels.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Ischemia; Cerebral Cortex; Chromonar; Eicosanoic Acids; Papaverine; Rats; Thromboxane B2; Thromboxanes; Vasodilator Agents

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Edema; Brain Ischemia; In Vitro Techniques; Male; Rats; Rats, Inbred SHR; Thiobarbiturates; Thromboxane B2

This study examines the pathophysiology of stroke secondary to focal cerebral ischemia. The interaction of arachidonic acid metabolites and polyamines, a class of ubiquitous ornithine-derived molecules with important membrane effects on edema, Ca++-dependent endocytosis, platelet function, and prostaglandin (PG) formation, are correlated with regional changes in H2 clearance, cerebral blood flow (rCBF), ischemic edema, and somatosensory evoked responses (SSERs) after middle cerebral artery (MCA) occlusion. Thirty cats were studied up to 3 hours before and 6 hours after right MCA occlusion. Four areas of brain showing different levels of perfusion after MCA occlusion were sampled for tissue levels of PGs: 6-keto-PGF1 alpha, PGE2, and as well as thromboxane B2 (TXB2), ornithine decarboxylase activity (ODC) (a measure of polyamine activity) and gravimetric determination of cerebral edema. After right MCA occlusion, right hemisphere SSER amplitude decreased and interpeak latency increased markedly. rCBF was distributed into zones of dense, partial, and no ischemia ranging from 12.6 to 59.4 ml/100 g/minute. Ischemic edema was distributed inversely to rCBF and was increased in areas of dense ischemia (85.2 +/- 0.5%) and ischemia (82.7 +/- 0.7%), but not in partially ischemic or control areas. 6-Keto-PGF1 alpha (1257.3 pg/mg), PGE2 (1628.5 pg/mg), and TXB2 (1572.8 pg/mg) were all significantly (P less than 0.05) increased in areas of partial ischemia that had not yet developed edema. ODC levels were significantly elevated (3812 pmole/g/hour, P less than 0.05) and increased with time in areas of slightly denser ischemia that showed an intermediate increase in edema, but not the presence of infarction. This is the first demonstration that ODC, the rate-limiting enzyme for polyamine synthesis, is stimulated by cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain Edema; Brain Ischemia; Cats; Cerebral Cortex; Dinoprostone; Evoked Potentials, Somatosensory; Ornithine Decarboxylase; Polyamines; Prostaglandins; Prostaglandins E; Regional Blood Flow; Thromboxane B2