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F Marzatico

Publications and source records attributed to F Marzatico.

At least 37 records · Page 2Linked to original sources
PubMed1993

Experimental Parkinson's disease in monkeys. Effect of ergot alkaloid derivative on lipid peroxidation in different brain areas.

The effects of the Parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated in four different monkey brain areas (frontal and occipital cortex, caudate putamen, substantia nigra). The basal and stimulated lipid peroxidation and the reduced glutathione (GSH) concentration were evaluated in three groups of male Macaca fascicularis monkeys (6 animals/group): (a) controls; (b) MPTP-treated animals; (c) animals treated with MPTP and alpha-dihydroergocryptine (DEK; ergot alkaloid characterized by a dopaminergic agonist action). In MPTP-treated animals the GSH concentration was unchanged or decreased in a non-significant way in the frontal and occipital cortex, and in substantia nigra. The basal thiobabituric acid reactive substance (TBARS) concentrations were significantly higher in the caudate putamen and substantia nigra of MPTP-treated animals. In the MPTP-treated monkeys the DEK administration induced a restoration of basal TBARS values to nearly normal ones. By incubating tissue from different brain areas with FeSO4 plus ascorbic acid, the stimulation of lipid peroxidation decreased the TBARS production in the substantia nigra of the MPTP-treated animals. These results, taken together, may indicate that an increased lipid peroxidation could possibly play a role in producing the Parkinson-like syndrome by MPTP and that a free radical excess could be responsible for the degeneration of the substantia nigra. The treatment with an ergot alkaloid (i.e., alpha-dihydroergocryptine) partially antagonizes the MPTP-induced increase in basal TBARS concentration in caudate putamen.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Antioxidant enzymatic activities after experimental subarachnoid hemorrhage in rats.

Lipid peroxidation has been hypotesized as one of possible factors involved in the pathogenesis of neuronal damage and delayed vasospasm after subarachnoid hemorrhage. In the brain there are anti-oxidant enzymatic systems which act as scavengers of superoxides and free radicals. In the present study the pattern of enzymatic anti-oxidant activities (Cu-Zn and Mn superoxide dismutase, and glutathione peroxidase) was investigated in an experimental model of subarachnoid hemorrhage in the rat in order to verify whether the hemorrhagic insult may be responsible for an impairment of such anti-oxidant systems. Enzymatic activities were assayed in three different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham-operated and at 30 min, 1, 6 and 48 h after subarachnoid hemorrhage induction. After the hemorrhage induction the Cu-Zn superoxide dismutase activity in cerebral cortex was significantly reduced at all the set times (p < .05), while Mn-superoxide dismutase activity was significantly decreased since 1 h (p < .05) until 48 h (p < .05). Glutathione peroxidase activity was significantly reduced only in the late phase (48 h) of subarachnoid hemorrhage (p < .01). In the hippocampus, all enzymatic activities were significantly reduced in the late phase. In the brain stem Cu-Zn superoxide dismutase was significantly impaired at 1 and 6 h (p < .05) after subarachnoid hemorrhage induction, while in the late phase (48 h) reached the control value. The mitochondrial Mn-superoxide dismutase was significantly reduced since 1 h (p < .05) until 48 h (p < .02) after subarachnoid hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Effect of high-dose methylprednisolone on anti-oxidant enzymes after experimental SAH.

Lipid peroxidation has been considered one of the most important factors involved in the pathogenesis of neuronal damage following subarachnoid hemorrhage. In the brain, the protective systems most involved against peroxidative and free radicals generated reactions are superoxide-dismutase (SOD) and glutathione-peroxidase (GSH-Px). Since these activities are subjected to a significant reduction following experimental SAH induction in rats, we investigated in the present study if the beneficial effect of high-dose methylprednisolone (MP) in inhibiting lipid peroxidative processes in SAH is possibly linked to an influence on anti-oxidant enzymatic activities. In brain cortex, after MP treatment, Cu-Zn SOD activity in the early phase and more dramatically in the late phase after SAH was restored (4.06 +/- 0.06 and 4.07 +/- 0.14 enzymatic units/mg of protein, respectively) if compared to hemorrhagic non-treated controls (3.69 +/- 0.16 and 2.96 +/- 0.06 enzymatic U/mg of protein) while Mn-SOD and GSH-Px activities were improved in treated animals only in the early and late phases after SAH, respectively. In the hippocampus, in treated rats Cu-Zn activity was partially restored only at 6 h, while Mn-SOD activity recovered at 48 h after SAH; no significant changes in GSH-Px activity were found in treated animals at any time. In the brain stem, in treated animals, Cu-Zn SOD activity was restored in the early phase (3.86 +/- 0.12 enzymatic U/mg of protein) up to control values of non-hemorrhagic rats (3.44 +/- 0.30 enzymatic U/mg of protein), while GSH-Px activity recovered in the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Correlation between electroencephalogram isoelectric time and hippocampal norepinephrine levels, measured by microdialysis, during ischemia in rats.

It is suggested that norepinephrine (NE) plays a role during transient forebrain ischemia. NE may have a protective action against neuronal cell death in the hippocampus, or it may be one of the causes of injurious ischemic effects. We used the microdialysis technique to study extracellular NE levels in the rat hippocampus before, during, and after 30 min of transient incomplete forebrain ischemia (induced by four-vessel occlusion) to describe the time course of NE in this condition. There was a maximal increase (fivefold) in extracellular NE after 10 min of reflow only when the electroencephalogram was isoelectric. NE levels returned to baseline 40 min after release of the carotid clamps and remained constant for the next 80 min. Thus there appears to be a transient NE overflow in the hippocampus during ischemia, closely related to the complete loss of brain electrical activity.

Animals↗
PubMed1992

Ex vivo release of eicosanoids after aneurysmal subarachnoid hemorrhage: a preliminary experience in humans.

Authors addressed the question whether the byosynthesis and the release of specific eicosanoids may occur in human brain cortex, and if the qualitative pattern of arachidonic acid metabolism is similar to that observed in experimental SAH. Human brain samples from 18 patients operated on for anterior communicating artery aneurysm (5 unruptured aneurysms considered as control cases, 7 patients operated on between Days 1 and 4 after SAH and 6 patients operated on between Days 10 and 14) were studied for the ex vivo release of 4 selected eicosanoids (Prostaglandin D2, E2, 6-keto-PGF1a and Leukotriene C4). Levels of arachidonate metabolites were determined by radioimmunoassay technique. PGD2 release is significantly lower in cases operated on delayed phase if compared to both control cases (p less than 0.05) and patients operated on in the acute phase, while there is no significant difference between the release of PGD2 in control cases and patients operated on in the acute phase. Release of 6-keto-PGF1a is significantly higher in patients operated on in a delayed phase (p less than 0.03 vs patients operated on in the acute phase and p less than 0.05 versus control cases). The release of LTC4 is significantly enhanced (p less than 0.05) in cases operated on in the acute phase if compared with unruptured aneurysms. The release of PGE2 is significantly enhanced in patients operated on in the acute phase (p less than 0.05) if compared to patients with unruptured aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Age-related acute depletion of cerebral glutathione by peroxidative stress.

Cyclohexene-1-one and cycloheptene-1-one cause a severe age-related depletion of reduced glutathione (GSH) in the forebrain of 5- or 15- or 25-month-old rats. Chronic pretreatment with phosphatidylcholine partially inhibits the GSH depletion in old forebrains by the prooxidants tested, suggesting that in aged animals alterations in mitochondrial inner membrane phospholipid composition and/or cytochrome oxidase activity might play a role in oxygen free-radical production.

Aging↗
PubMed1991

Sequential damage in mitochondrial complexes by peroxidative stress.

The biochemical characteristics of the electron transfer chain are evaluated in purified non-synaptic ("free") mitochondria from the forebrain of 60-week-old rats weekly subjected to peroxidative stress (once, twice, or three times) by the electrophilic prooxidant 2-cyclohexene-1-one. The following parameters are evaluated: (a) content of respiratory components, namely ubiquinone, cytochrome b, cytochrome c1, cytochrome c; (b) specific activity of enzymes, namely citrate synthase, succinate dehydrogenase, rotenone-sensitive NADH: cytochrome c reductase, cytochrome oxidase; (c) concentration of reduced glutathione (GSH). Before the first peroxidative stress induction, the rats are administered for 8 weeks by intraperitoneal injection of vehicle, papaverine, delta-yohimbine, almitrine or hopanthenate. The rats are treated also during the week(s) before the second or third peroxidative stress. The cerebral peroxidative stress induces: (a) initially, a decrease in brain GSH concentration concomitant with a decrease in the mitochondrial activity of cytochrome oxidase of aa3-type (complex IV), without changes in ubiquinone and cytochrome b populations; (b) subsequently, an alteration in the transfer molecule cytochrome c and, finally, in rotenone-sensitive NADH-cytochrome c reductase (complex I) and succinate dehydrogenase (complex II). The selective sensitivity of the chain components to peroxidative stress is supported by the effects of the concomitant subchronic treatment with agents acting at different biochemical steps. In fact, almitrine sets limits to its effects at cytochrome c content and aa3-type cytochrome oxidase activity, while delta-yohimbine sets limits to its effects at the level of tricarboxylic acid cycle (citrate synthase) and/or of intermediary between tricarboxylic acid cycle and complex II (succinate dehydrogenase).(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine↗
PubMed1991

Effects of nicardipine treatment on Na(+)-K+ ATPase and lipid peroxidation after experimental subarachnoid haemorrhage.

The calcium theory of neuronal damage has been recently adapted to subarachnoid haemorrhage (SAH). It is proposed that haemorrhagic insult to the brain causes free radical-mediated destructive reactions of membrane phospholipids, and the consequent decrease of phospholipid-dependent enzymatic activities, such as Na(+)-K+ ATPase. In the present study we have studied the effects of Nicardipine treatment on lipid peroxidation and Na(+)-K+ ATPase activity after experimental induction of SAH. SAH was induced in anaesthesized rats by slow injection of 0.3 ml of autologous arterial blood into the cisterna magna. We assessed the extent of lipid peroxidation by measuring the level of thiobarbituric acid reactive substances (TBARS) and Na(+)-K+ ATPase activity in 3 different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham-operated (0.3 ml of mock CSF into cisterna magna) and at 1 hour, 6 hours and 48 hours after SAH induction; simultaneously, we investigated the capacity of cerebral lipid peroxidation by measuring the accumulation of TBRAS in homogenates of brain areas incubated under aerobic conditions. Na(+)-K+ ATPase activity decreased in the cerebral cortex at 1 hour and 6 hours and in brain stem at 1 hour after SAH, while the same enzymatic activity did not change in the hippocampus. There was no significant difference in lipid peroxide content between sham-operated and haemorrhagic animals; Nicardipine treatment reduced the TBRAS content and induced the recovery of Na(+)-K+ ATPase activity, exerting a brain protective role against the detrimental effects of the haemorrhage.

Animals↗
PubMed1991

"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.

The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Animals↗
PubMed1990

Influence of oxidative stress on the age-linked alterations of the cerebral glutathione system.

The glutathione system (reduced and oxidized glutathione; redox index) was studied in the forebrain of male Wistar rats of 5, 15, and 25 months of age following the administration for 2 months in drinking water of chemicals that induce oxidative stress: paraquat and diethyldithiocarbamate (DDC) to increase superoxide radical formation, aminotriazole and hydrogen peroxide to increase hydroxyl radical generation, as well as diamide and ferrous chloride to decrease the glutathione cycle activity. Chronic oral administration of phosphatidylcholine for 2 months was evaluated in 25-month-old rats. Aging accentuated the changes produced by chemicals that induce oxidative stress; i.e., the changes in the glutathione redox index were most pronounced in the forebrains of the older paraquat-, DDC-, H2O2-, and diamide-treated rats. Markedly different adaptative changes occurred within the various drug groups. The reduced glutathione was increased (by paraquat, DDC and aminotrazole), decreased (by H2O2) or unchanged (by iron and diamide). Furthermore, in older rats, paraquat and DDC increased the glutathione redox index, whereas H2O2 and diamide decreased the glutathione redox index or were ineffective (i.e., aminotriazole, iron). The glutathione redox index altered by chronic drug administration was modified by the concomitant administration of phosphatidylcholine.

Administration, Oral↗
PubMed1990

Influence of aging and drug treatment on the bioenergetics of hypoxic brain.

Synaptosomes isolated from the forebrain of rats of different ages (20, 60 and 100 weeks of age) were incubated in Krebs-Henseleit-Hepes (pH 7.4) buffer, for 10 min at 24 degrees C. The energetic state was defined by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The biological energy "lost" by the system during the coupled reactions was estimated by the delta delta G = delta Gox-red - delta GATP. The animals were submitted for 10 min to different degrees of in vivo hypoxia. To elucidate the mechanism of action, the effect of the pretreatment with drugs acting on oxygen availability (almitrine) or on microcirculation and metabolism (delta-yohimbine) was tested. In synaptosomes isolated from the forebrain of animals submitted to moderate degree of hypoxia (oxygen arterial partial pressure ranging between 32 and 29 mmHg) the efficiency of the system was quite similar to that observed in normoxia, with the exception of the older rats. In synaptosomes isolated from the forebrain of rats submitted to severe degree of hypoxia (oxygen arterial partial pressure ranging between 20 and 18 mmHg) the efficiency of the system was markedly altered as a function of both aging and severity of hypoxemia. The pretreatment with the agent increasing the oxygen availability partially modified the efficiency of the system, the alpha-blocking agent being less important. The drug action was markedly related to both the age and the degree of hypoxia.

Adenosine Triphosphate↗
PubMed1990

Factors involved in the age-related alteration in the efficiency of the brain bioenergetics.

The synaptic energy state may be defined by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The biological energy 'lost' by the system during the coupled reactions is calculated as delta delta G = delta Gox-red-delta GATP. These evaluations are performed in synaptosomes isolated from the forebrain of rats of different ages (20, 60 and 100 weeks of age) and incubated in Krebs-Henseleit-Hepes (pH 7.4) buffer, for 10 min at 24 degrees C. The animals are submitted for 10 min to different degrees of in vivo hypoxia. To better elucidate the mechanism of action, the effects of the pretreatment with agents inducing vasodilation (papaverine), or acting on cerebral carbohydrate metabolism (hopanthenate), or on neurotransmission and cerebral metabolism (theniloxazine) are tested. In synaptosomes isolated from the forebrain of animals submitted to moderate degree of hypoxia (PaO2 = 32-29 mmHg) the efficiency of the system is quite similar to that observed in normoxia, with the exception of the older rats. In synaptosomes isolated from the forebrain of rats submitted to severe degree of hypoxia (PaO2 = 20-18 mmHg) the efficiency is altered as a function of both aging and severity of hypoxemia. Drug pretreatment may partially interfere with the delta delta G by hypoxemia, the action being related to the rat age and hypoxic degrees. The age-related decrease in the efficiency of the coupled states seems to be related to alteration in the phosphorylation state of adenine nucleotides.

Adenine Nucleotides↗
PubMed1990

Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase.

Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy.

Analysis of Variance↗
PubMed1990

High-dose methylprednisolone and 'ex vivo' release of eicosanoids after experimental subarachnoid haemorrhage.

In the present study we have investigated the effects of high-dose methylprednisolone (MP) treatment on the 'ex vivo' release of four major eicosanoids in an experimental model of subarachnoid haemorrhage (SAH) with the aim of verifying: (a) the efficacy in reducing arachidonic acid metabolism enhancement; (b) whether high-dose methylprednisolone is effective on both the cyclooxygenase and lipoxygenase pathways; and (c) discussing the possible role of high-dose MP treatment in brain protection after SAH. Levels of prostaglandin D2 and E2, prostacyclin and also leukotriene C4 were determined by the radioimmunoassay technique after 1 h incubation of cerebral cortex samples of rats which had been subjected to experimental SAH procedure (injection of 0.3 ml of autologous arterial blood). The release of prostaglandin D2 at 48 h after SAH is significantly higher when compared to that of sham-operated animals (P less than 0.01); prostaglandin E2 release is significantly enhanced at 6 h after the SAH procedure (P less than 0.01); release of the lipoxygenase metabolite is significantly enhanced at 1, 6 and 48 h after SAH induction; MP significantly decreases the release of all eicosanoids, and values in treated animals do not differ from those of sham-operated animals. The results of the present study suggest that the global inhibitory effect of high-dose MP treatment on the 'ex vivo' release of eicosanoids after experimental SAH could be considered to be one of the neurochemical correlates for the reduced incidence and severity of arterial inflammatory response, which results in chronic vasospasm and supports the clinical evidence of MP efficacy in preventing or reducing the incidence of arterial vasospasm after aneurysmal rupture.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effects of high-dose methylprednisolone on Na(+)-K+ ATPase and lipid peroxidation after experimental subarachnoid hemorrhage.

The production of oxygen-free radicals and their subsequent peroxidative action on membrane unsaturated fatty acids could be enhanced after subarachnoid hemorrhage. High-dose methylprednisolone (30 mg/Kg i.v.) treatment can antagonize acute SAH-induced brain hypoperfusion and protect the ultrastructural integrity of endothelial cell membranes. Experimental subarachnoid hemorrhage (SAH) was induced in anesthesized rats by slow injection of 0.3 ml of autologous arterial blood into cisterna magna. Tissue lipid peroxidation, quantified as thiobarbituric acid reactive material (TBAR) and Na(+)-K+ ATPase activity were assayed in three different rat brain areas (cerebral cortex, hippocampus and brain stem) of controls (without any surgical manipulation), sham-operated (0.3 ml. of mock CSF into cisterna magna) and after SAH induction, at 1 h, 6 h and 48 h. Na(+)-K+ ATPase activity decreased in the cerebral cortex at 1 h and 6 h and in brain stem at 1 h after SAH, while the same enzymatic activity was unchanged in the hippocampus. High-dose methyl-prednisolone treatment (started immediately after SAH induction) enhanced the Na(+)-K+ ATPase activity until control levels. There was no significant difference in lipid peroxide content between sham-operated and hemorrhagic animals; however, the injection itself induces a transient increase of TBAR (1 h after injection) and methylprednisolone treatment decreases the products of lipid peroxidation in all brain areas.

Animals↗
PubMed1990

Arachidonic acid metabolism and pathophysiologic aspects of subarachnoid hemorrhage in rats.

We studied the ex vivo production of prostaglandin D2, prostaglandin E2, 6-ketoprostaglandin F1 alpha, and leukotriene C4 in the brain tissue of rats subjected to experimental subarachnoid hemorrhage. The ex vivo method allows the study of arachidonic acid metabolites released from brain slices at different times after subarachnoid hemorrhage induction and reflects the residual capacity for arachidonic acid metabolism after the pathologic event. The rats were sacrificed 30 minutes, 1 and 6 hours, and 2 days after subarachnoid hemorrhage was induced by the injection of 0.30 ml autologous arterial blood into the cisterna magna. Concentration of prostaglandin D2 and 6-ketoprostaglandin F1 alpha was increased significantly relative to control 2 days after induction. The concentration of prostaglandin E2 was increased significantly 6 hours after induction, while ex vivo production of leukotriene C4 was increased significantly at 1 and 6 hours and 2 days. The correlation between these results and the occurrence of vasospasm after subarachnoid hemorrhage is discussed. The results obtained from the ex vivo incubation of brain tissue slices after experimental subarachnoid hemorrhage suggest that after the hemorrhage there is a significant modification of brain eicosanoid metabolism, which could be of great importance in interpreting the pathogenesis of subarachnoid hemorrhage-related neuronal impairment.

Animals↗