thromboxane-b2 and Brain-Edema

Traumatic brain injury (TBI) is the main cause of trauma-related deaths. Systemic hypotension and intracranial hypertension causes cerebral ischemia by altering metabolism of prostanoids. We describe prostanoid, pupilar and pathological response during resuscitation with hypertonic saline solution (HSS) in TBI. Method Fifteen dogs were randomized in three groups according to resuscitation after TBI (control group; lactated Ringer's (LR) group and HSS group), with measurement of thromboxane, prostaglandin, macroscopic and microscopic pathological evaluation and pupil evaluation.Result Concentration of prostaglandin is greater in the cerebral venous blood than in plasma and the opposite happens with concentration of thromboxane. Pathology revealed edema in groups with the exception of group treated with HSS.Discussion and conclusion There is a balance between the concentrations of prostaglandin and thromboxane. HSS prevented the formation of cerebral edema macroscopically detectable. Pupillary reversal occurred earlier in HSS group than in LR group.

Topics: Animals; Brain; Brain Edema; Brain Injuries; Cerebrovascular Circulation; Dogs; Fluid Therapy; Hemodynamics; Intracranial Pressure; Isotonic Solutions; Male; Prostaglandins F; Pupil; Random Allocation; Reproducibility of Results; Ringer's Lactate; Saline Solution, Hypertonic; Shock, Hemorrhagic; Thromboxane B2; Time Factors; Treatment Outcome

Hypertensive basal ganglia hemorrhage (HBGH) accounts for 35%-44% of cases of hypertensive intracranial hemorrhage (ICH), which is one of the most devastating forms of cerebrovascular disease. In this study, intracerebral hematoma was evacuated with a burr hole craniectomy. The relationships of residue hematoma volume to brain edema, inflammation factors and the long-term prognosis of HBGH patients were studied.. One hundred and seventy-six patients with HBGH were randomly divided into gross-total removal of hematoma (GTRH) and sub-total removal of hematoma (STRH) groups. The pre-operative and post-operative data of the patients in the two groups were compared. The pre-operative data included age, sex, hematoma volume, time from the ictus to the operation, Glasgow Coma Scale (GCS) scores, and the European Stroke Scale (ESS) scores. The post-operative information included edema grade, level of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a (6-K-PGF1a), tumor necrosis factor-a (TNF-a) and endothelin (ET) in hematoma drainage or cerebral spinal fluid (CSF), ESS and Barthel Index (BI).. There was no statistical difference between the two groups (P>0.05) in the pre-operative data. The levels of TXB2, 6-K-PGF1a, TNF-a and ET in the GTRH group were significantly lower than those in the STRH group at different post-operative times. The ESS in the GTRH group increased rapidly after the operation and was higher than that in the STRH group. There was a significant difference between the two groups (P<0.05). The post-operative CT scan at different times showed that the brain edema grades were better in the GTRH group than in the STRH group. The BI was higher in the GTRH group than in the STRH group (P<0.05).. GTRH is an effective method to decrease ICH-induced injury to brain tissue. Such effect is related to decreased perihematomal edema formation and secondary injury by coagulation end products activated inflammatory cascade.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Basal Ganglia Hemorrhage; Biomarkers; Brain Edema; Disease Progression; Encephalitis; Endothelins; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Hypertension; Inflammation Mediators; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Predictive Value of Tests; Prognosis; Thromboxane B2; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

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

Dietary docosahexaenoic acid (DHA) intake can decrease the level of membrane arachidonic acid (AA), which is liberated during cerebral ischemia and implicated in the pathogenesis of brain damage. Therefore, in the present study, we investigated the effects of chronic ethyl docosahexaenoate (E-DHA) administration on mortality and cerebral edema induced by transient forebrain ischemia in gerbils. Male Mongolian gerbils were orally pretreated with either E-DHA (100, 150 mg/kg) or vehicle, once a day, for 4 weeks and were subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. The content of brain lipid AA at the termination of treatment, the survival ratio, change of regional cerebral blood flow (rCBF), brain free AA level, thromboxane B(2) (TXB(2)) production and cerebral edema formation following ischemia and reperfusion were evaluated. E-DHA (150 mg/kg) pretreatment significantly increased survival ratio, prevented post-ischemic hypoperfusion and attenuated cerebral edema after reperfusion compared with vehicle, which was well associated with the reduced levels of AA and TXB(2) in the E-DHA treated brain. These data suggest that the effects of E-DHA pretreatment on ischemic mortality and cerebral edema could be due to reduction of free AA liberation and accumulation, and its metabolite synthesis after ischemia and reperfusion by decreasing the content of membrane AA.

Topics: Animals; Arachidonic Acid; Body Water; Brain; Brain Chemistry; Brain Edema; Cerebrovascular Circulation; Docosahexaenoic Acids; Fatty Acids; Gerbillinae; Ischemic Attack, Transient; Male; Survival Analysis; Thromboxane B2

The present study was designed to prospectively investigated the prostaglandin (PG) levels and extent of peritumoral edema in 30 cases of glioma by using methods of radioimmunoassay and imaging. Both TXB2 and 6-keto-PGF1 alpha levels in all glioma groups went up over that in the control group. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were markedly increased with the extent of tumor malignancy. Water concentration in anaplastic astrocytoma and glioblastoma were significantly elevated. Difference in TXB2 level and TXB2/6-keto-PGF1 alpha ratio among three edema grades were statistically significant. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were closely correlated with water concentration (r1 = 0.53, r2 = 0.72, P < 0.01). Our findings suggested that the metabolism of PG in glioma were in the state of disorder, and that the imbalance between PGI2 and TXA2 may be one of factors which affect the formation of peritumoral edema.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Astrocytoma; Brain Edema; Brain Neoplasms; Epoprostenol; Female; Glioblastoma; Humans; Male; Middle Aged; Prospective Studies; 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

Methylprednisolone was recently reported to significantly improve motor and sensory function after acute spinal cord injury in patients. Our study was designed to determine whether methylprednisolone exerts a beneficial effect after head injury. Diethyl ether-anesthetized rats were assigned to receive surgery with no cranial impact and no methylprednisolone (group A, n = 13); surgery with no cranial impact and intraperitoneal methylprednisolone (greater than or equal to 60 mg/kg) (group B, n = 8); surgery with cranial impact and no methylprednisolone (group C, n = 8, and group E, n = 8); or surgery with cranial impact and methylprednisolone (greater than or equal to 60 mg/kg) (group D, n = 15, and group F, n = 13). Neurologic severity score was determined at 1, 2, 4, and 24 h (when appropriate) after injury, and brain tissue eicosanoid levels and cerebral edema were determined when the animals were killed (4 h after injury in groups C and D and 24 h after injury in groups E and F). Treatment with methylprednisolone did not improve neurologic severity score or edema formation and did not alter brain tissue levels of prostaglandin E2, thromboxane B2, or 6-keto-prostaglandin F1 alpha at any time period. The authors conclude that methylprednisolone does not exert a beneficial effect on brain tissue edema or functional activity after cranial impact in rats.

Topics: Animals; Brain; Brain Edema; Craniocerebral Trauma; Male; Methylprednisolone; Nervous System Diseases; Prostaglandins; Rats; Thromboxane B2

Brain tumours produce prostaglandins in vitro; their in vivo production has been studied by determining the levels of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha and thromboxane B2 in tumour cyst fluid and ventricular CSF taken from 21 patients with a variety of intracranial tumours. The levels were high in tumour cyst fluid but there was no overall increase in ventricular CSF. Hence, brain tumours do not produce a consistent pattern of abnormality of eicosanoid concentrations in the ventricular CSF that would be useful for diagnosis. If brain tumours produce excess quantities of these prostaglandins in vivo as they do in vitro, these prostaglandins may be rapidly cleared by the cerebral microvasculature unless compartmentalized within a tumour cyst.

Topics: 6-Ketoprostaglandin F1 alpha; Body Fluid Compartments; Body Fluids; Brain Edema; Brain Neoplasms; Dinoprost; Dinoprostone; Eicosanoids; Female; Humans; Hydrocephalus; Intervertebral Disc Displacement; Male; Thromboxane B2

Head trauma (HT) was induced in the left hemisphere of rats by a weight drop device. Edema was maximal 24 h after HT in the injured zone, and PGE2, TXB2 and 6-keto-PGF1 alpha were elevated in both the injured and remote areas. The effect of a specific thromboxane synthetase inhibitor, OKY-046, on the outcome of HT was studied. OKY-046, 100 mg/kg, was given to rats immediately and 8 h after HT. The neurological severity score (NSS) was evaluated at 1 h after HT, and at 24 h, just prior to sacrifice. Specific gravity (SG) of both hemispheres was measured after decapitation. Prostaglandins (PGs) were extracted from the site of injury and from the frontal lobes, remote from the injury, and assayed by RIA. Basal levels of PGE2 and 6-keto-PGF1 alpha were not reduced by the drug while basal TXB2 levels were lowered. However, the increased production due to HT of all PGs, was inhibited by OKY-046, especially that of TXB2. The ratio of TXB2/6-keto-PGF1 alpha, known to affect vascular tone, was reduced by OKY-046 treatment as a result of TXA2 synthesis inhibition. Still, no effect was found on the neurological outcome (as evaluated by the NSS), or on edema formation (expressed by reduced SG). Thus, based on the present findings increased TXA2 synthesis cannot be implicated in the pathophysiology of cerebral edema or dysfunction following HT.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Animals; Brain Edema; Brain Injuries; Dinoprostone; Male; Methacrylates; Rats; Specific Gravity; Thromboxane B2; Thromboxane-A Synthase

Previous studies have indicated that the regional distribution of the arachidonic acid metabolites around a focal ischemic lesion may be important in the pathogenesis of cerebral ischemia. To determine the functional significance of this regionalization, we examined the effect of imidazole (a thromboxane synthetase inhibitor) on the distribution of the vasoconstrictor thromboxane and the vasodilators prostacyclin and prostaglandin E2 (PGE2) and on the distribution of cerebral blood flow (CBF) around a focal ischemic lesion, middle cerebral artery (MCA) occlusion in the cat. The study was conducted in two phases. The first phase examined regional distribution of tissue arachidonic acid metabolites and the effect of imidazole treatment on that distribution. The second phase examined the effect of imidazole treatment on the distribution of blood flow about the focal ischemic lesion as well as on electrocortical function and edema production. MCA occlusion resulted in increased thromboxane, prostacyclin, and PGE2 levels in the ipsilateral hemisphere. These increases were greatest in the region of marginal ischemia and were present both 3 and 6 hours after occlusion. Imidazole pretreatment (50 mg/kg i.p.) significantly inhibited thromboxane production, but augmented production of prostacyclin and PGE2. In the blood flow studies, imidazole was without effect on regions of dense cerebral ischemia (CBF less than 20 ml/minute/100 g for more than 12 of 24 postocclusion hours). In regions of marginal ischemia (20 less than CBF less than 30 ml/minute/100 g for more than 12 of 24 postocclusion hours), imidazole pretreatment significantly increased blood flow in both gray and white matter compared with saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Brain; Brain Edema; Cats; Cerebrovascular Circulation; Dinoprostone; Evoked Potentials, Somatosensory; Imidazoles; Ischemic Attack, Transient; Prostaglandins E; Thromboxane B2; Thromboxane-A Synthase

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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Benzoquinones; Body Water; Brain; Brain Edema; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Susceptibility; Eicosanoic Acids; Hypertension; Male; Quinones; Rats; Rats, Inbred SHR; SRS-A; Thromboxane B2

Head injury was induced in the left hemisphere of rats. The rats were killed at various time intervals after trauma (immediately, 15 min, 1 and 18 h, and 4 and 10 days), and the rates of synthesis and release of prostaglandin PGE2, 6-keto-PGF1 alpha, and thromboxane TXB2 from cortical slices of both hemispheres were studied. The rate of synthesis of PGE2 after 18 h was six and four times higher than control in the contused and contralateral hemispheres, respectively. By 10 days post-trauma, both hemispheres had normal rate of PGE2 release. TXB2 and 6-keto-PGF1 alpha synthetases were affected already 15 min after the injury, and a similarly elevated rate of synthesis was found in both hemispheres. The maximal effect was detected after 1 or 18 h with return to normal after 4 or 10 days for TXB2 and 6-keto-PGF1 alpha, respectively. Tissue specific gravity was determined for both hemispheres using linear gradient columns. The results of these determinations indicate that development of edema occurs in the contused hemisphere as early as 15 min post trauma; it reaches its maximal level at 18 h and returns to normal at 10 days. Arterial pressure was monitored, and a transient increase was found at 10 min post trauma. We suggest that the production of edema after brain injury may be related to the increased rate of PGE2 and PGI2 synthesis, which occurs at similar time intervals after injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Brain; Brain Edema; Craniocerebral Trauma; Dinoprostone; Male; Prostaglandins; Prostaglandins E; Rats; Thromboxane B2

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