thromboxane-b2 and Spinal-Cord-Injuries

This study investigates how strenuous arm exercise affects oxidized-low density lipoprotein (O(X)-LDL) mediated-platelet activation in patients with SCI. Ten patients with SCI and ten age- and sex-matched healthy subjects exercised strenuously using an arm crank ergometer. The following measurements were taken both when the subjects were at rest, and immediately after exercise: plasma lipid profile, O(X)-LDL mediated platelet aggregability and [Ca(2+)]i, urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 8-iso-prostaglandin F(2alpha), (8-iso-PG F(2alpha)) contents, and plasma NO metabolite (nitrite plus nitrate) level. Based on these measurements, the major findings of this study can be summarized as follows: 1) the SCI group had higher urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB2 contents, but a lower plasma nitrite plus nitrate level than the control group; 2) at rest, the SCI group had a higher platelet aggregability and [Ca(2+)]i, and O(X)-LDL-potentiated platelet activation than the control group; 3) O(X)-LDL-potentiated platelet aggregation was enhanced by strenuous arm exercise in both groups, but the effect of exercise was more pronounced in the SCI group than in the control group; 4) treating the platelet with L-arginine inhibited O(X)-LDL-potentiated platelet activation in both groups. The study concludes that individuals with SCI had more extensive resting and exercise-enhanced O(X)-LDL-potentiated platelet activation and greater amounts of preformed lipid peroxides than those without SCI. Therefore, supplementation therapy with antioxidants may be needed for patients with SCI, especially in a strenuous arm exercise period.

Topics: Adult; Arm; Arteriosclerosis; Calcium; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dinoprost; Exercise Test; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Platelet Activation; Platelet Aggregation; Platelet Count; Risk Factors; Spinal Cord Injuries; Thromboxane B2

In order to understand the relation between TXA2-PGI2 and secondary trauma and the effect of intra-arachnoid perfusion of dexamethasone and verapamil on alteration of TXA2-PGI2 following spinal cord injury, TXB2 and 6-keto-PGF alpha concentration and pathological changes in injured site 1, 2, 4, and 6 h after injury were studied using a rabbit spinal cord injury model by Allen's weight drop method.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Calcium Channel Blockers; Dexamethasone; Injections, Spinal; Male; Rabbits; Spinal Cord Injuries; Thromboxane B2; Verapamil

In an attempt to elucidate a possible role for eicosanoids in the pathogenesis of spinal cord injury (SCI), we measured the concentration of leukotriene (LT) C4, thromboxane B2, and 6-keto-prostaglandin F1 alpha in cerebrospinal fluid in both a canine experimental model and 11 patients with SCIs.. The eicosanoid concentration in cerebrospinal fluid was measured by radioimmunoassay. Neurological severity was assessed according to the grading system of Frankel et al.. Control samples were obtained from 20 patients without SCIs.. In the canine model, a significant increase in all eicosanoid levels was found on Days 1 to 7, which subsequently returned to the control levels. In the clinical study, the highest mean (+/- standard error of the mean) concentrations of LTC4, thromboxane B2, and 6-keto-prostaglandin F1 alpha in the acute stage of SCI were 95.9 +/- 10.7, 175.2 +/- 38.2, and 167.5 +/- 39.9 pg/ml, respectively. These concentrations were five to nine times higher than control levels. There was a good correlation between cerebrospinal fluid LTC4 levels and the neurological severity. The time-dependent change in LTC4 concentrations in seven patients with SCIs was similar to that observed in the canine model. In addition, the highest mean concentrations of the eicosanoids measured in patients with complete paralysis was also similar to those of the canine model. The eicosanoid concentrations in five patients with SCI were measured more than 6 months after the onset of injury. Although all eicosanoid levels had elevated in the acute stage of injury, they were not elevated and showed the same levels as the controls at the chronic stage.. The findings suggest that enhanced arachidonate metabolism occurs in humans and support the evidence from animal experiments that emphasizes the importance of eicosanoids in the secondary processes mediating ischemia and edema.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Animals; Dogs; Female; Humans; Leukotriene C4; Male; Methylprednisolone; Middle Aged; Neuroprotective Agents; Osmolar Concentration; Spinal Cord Injuries; Thromboxane B2; Time Factors

Platelet activating factor (PAF) and PAF receptor antagonist BN52021 were respectively administered by intrathecal or intravenous injection in cats. We observed their effects on blood flow and TXB2/ 6-keto-PGF1 alpha ratio (T/K ratio) in injured spinal cord and its adjacent region (L2-L4)s after trauma. The results showed that gray matter and white matter blood flow at L2-L4 segment significantly decreased T/K ratio elevated evidently in PAF group as compared with simple spinal cord injury, while gray matter and white matter blood flow at L2-L4 segment significantly increased and T/K ratio markedly decreased in BN52021 group as compared with simple spinal cord injury group. The results demonstrate and that PAF is an important factor leading to spinal cord blood flow reduction after trauma, and that PAF receptor antagonist BN52021 can evidently improve spinal cord blood flow and relieve secondary damage after trauma.

Topics: Animals; Cats; Diterpenes; Female; Ginkgolides; Injections, Spinal; Lactones; Male; Platelet Activating Factor; Prostaglandins F; Regional Blood Flow; Spinal Cord; Spinal Cord Injuries; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; beta-Thromboglobulin; Blood Coagulation Tests; Catecholamines; Cyclic AMP; Female; Fibrinolysis; Hemodynamics; Humans; Incidence; Male; Platelet Aggregation; Quadriplegia; Spinal Cord Injuries; Thrombophlebitis; Thromboxane B2

Acute alcohol intoxication may exacerbate the consequences of central nervous system trauma, although the mechanism is uncertain. Effects of acute ethanol administration on behavioral and neurochemical changes were examined in rats after traumatic spinal cord injury. Survival rates were reduced and posttraumatic neurologic function worsened in ethanol-treated as compared with saline-treated controls. Ethanol-treated rats had significantly lower tissue levels of excitatory amino acids and higher levels of free fatty acids, thromboxane, and lactic acid than did controls. Tissue magnesium concentration was significantly reduced by trauma and recovered more slowly in ethanol-treated rats. Enhanced phospholipid hydrolysis with free fatty acid and thromboxane accumulation, increased release of excitatory amino acids, and decreased tissue magnesium levels may each serve to worsen secondary tissue damage and diminish neurologic recovery after spinal cord injury associated with acute alcohol intoxication.

Topics: Amino Acids; Animals; Behavior, Animal; Body Water; Cations; Cholesterol; Ethanol; Fatty Acids, Nonesterified; Lactates; Lactic Acid; Laminectomy; Rats; Spinal Cord Injuries; Thromboxane B2

Thromboxane A2 (TXA2) is an eicosanoid with potent platelet aggregation and vasoconstricting activity, while prostaglandin I2 (PGI2) antagonizes its activity. But these eicosanoids are so labile that the stable degradation products, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), are determined in biological materials. In a rat spinal cord compression injury model, a production of TXB2 reached a peak (133.6 +/- 13.8 pmol/g cord) 5 minutes after compression injury, while that of 6-keto-PGF1 alpha slightly increased (26.2 +/- 11.7 pmol/g cord). And the magnitude of the increase in TXB2 and the extent of post-traumatic vascular damage as determined by fluorescein uptake were both dependent on the degree of spinal cord compression injury. We also studied the effect of a selective TXA2 synthetase inhibitor, OKY-046 [E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid), both on TXB2 production in the injured spinal cord and post-traumatic vascular damage. When OKY-046 was administered intravenously 10 minutes prior to compression injury at a dose of 500 micrograms/kg body weight, the increased production of TXB2 was inhibited by about 80% and uptake of sodium fluorescein was reduced by a maximum of 40%. When the compression injury was induced before OKY-046 was administered, the inhibitory effect of OKY-046 on TXB2 production decreased depending on the duration before administration. In contrast, the 6-keto-PGF1 alpha level was not affected in the presence of OKY-046.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Animals; Blood Vessels; Depression, Chemical; Fluoresceins; Male; Methacrylates; Rats; Rats, Inbred Strains; Spinal Cord; Spinal Cord Compression; Spinal Cord Injuries; Thromboxane B2; Thromboxane-A Synthase

A total of 118 patients with cervical spinal cord injury were studied to determine the neurologic improvement achieved by either conservative or surgical treatment. Useful recovery was observed in 55% of the patients with incomplete cord injuries, but in none of those with complete cord injuries. There was no significant difference between the treatment groups regarding neurologic improvement. In experimental studies on rats, the increased levels of lipid peroxides and thromboxane after spinal cord injury were found to be proportional to the magnitude of injury. These evidences suggest that spinal cord injury is directly related with the magnitude of injury, and the prognosis is determined entirely at the time of injury.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Female; Free Radicals; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Methacrylates; Prognosis; Rats; Spinal Cord; Spinal Cord Injuries; Thromboxane B2; Thromboxane-A Synthase

BW755C is an inhibitor of both cyclo-oxygenase and lipoxygenase, which has been found to have protective effects after myocardial ischemia in dogs. Impact injury to the spinal cord is associated with tissue ischemia as well as with the accumulation of eicosanoids. In the present studies we evaluated the effects of BW755C after traumatic spinal cord injury in rats. Drug treatment reduced thromboxane B2 levels and improved neurological recovery as compared to treatment with equal-volume physiological saline. The findings suggest that this drug or related compounds may be useful for the treatment of clinical spinal cord injury.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Animals; Enzyme Inhibitors; Lipoxygenase; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Inbred Strains; Spinal Cord Injuries; Thromboxane B2

Thromboxane-prostacyclin imbalance may be an important determinant of platelet-vessel wall interactions that are vital in circulatory homeostasis. In experimental spinal cord injury, the vascular damage contributes substantially to the process of progressive secondary injury culminating in post-traumatic myelopathy. In this study, we found a time-dependent alteration of thromboxane-prostacyclin balance in the injured spinal cord with thromboxane dominance during the first 2 h: a time when maximal vascular injury is reflected by extravasation of 125I-labelled serum albumin. The thromboxane-prostacyclin imbalance reverted to favor prostacyclin by 18 h post-injury. This time-dependent alteration of thromboxane-prostacyclin balance should be considered in the planning of therapeutic attempts to prevent secondary injury by pharmacological modulation of platelet-vessel wall interaction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessels; Homeostasis; Kinetics; Rats; Rats, Inbred Strains; Serum Albumin; Spinal Cord; Spinal Cord Injuries; Thromboxane B2; Time Factors

Spinal cord samples from rats subjected to three different levels of impact trauma (25, 50, 100 g-cm) were examined for immunoreactive thromboxane B2 and 6-sulfidopeptide-containing leukotrienes, using specific radioimmunoassays. Trauma resulted in pronounced increases in thromboxane levels as early as 5 min after injury, with maximum values at 1 hr. Although thromboxane values then slowly declined, they remained significantly above control values for up to 7 days. Significantly smaller thromboxane values were found in rats subjected to mild injury (25 g-cm) than in those that received more severe, irreversible impact injury (50 and 100 g-cm). No statistically significant changes were observed in leukotriene levels in any of the experimental groups. These findings are consistent with the hypothesis that cyclooxygenase products of arachidonic acid metabolism may contribute to secondary injury after spinal cord trauma and provides the rationale for the use of cyclooxygenase inhibitors in the treatment of such injury.

Topics: Animals; Kinetics; Male; Rats; Reference Values; Spinal Cord; Spinal Cord Injuries; SRS-A; Thromboxane B2; Time Factors

Eicosanoids are known mediators of inflammation, vascular permeability, and are involved in microcirculatory blood flow regulation. To study their potential involvement in the pathophysiology of CNS trauma we used a rabbit spinal cord trauma model. Rabbits were subjected to lumbar spinal cord trauma produced by a modification of the Allen weight-drop method. TXB2, 6-keto-PGF1 alpha, PGE2, and 5-hydroxyeicosatetraenoic acid (5-HETE) release from spinal cord slices incubated ex vivo were measured by radioimmunoassay at 5, 30 min, 24 hrs, and 2 wks after trauma. Five and 30 min after trauma the TXB2/6-keto-PGF1 alpha ratio was elevated and the release of 5-HETE at 5 min after trauma increased in the injured spinal cord whereas release of 6-keto-PGF1 alpha and PGE2 remained at base-line levels. In the thoracic spinal cord, TXB2 and 6-keto-PGF1 alpha release were increased at 30 min after trauma. Release of 5-HETE from the injured spinal cord was also elevated 24 hrs after trauma. Two wks after trauma, TXB2 and 6-keto-PGF1 alpha release were also elevated in the injured spinal cord. Measurements of tissue water content by microgravimetry indicated progressive edema in the injury site while histopathological evaluation indicated progressive damage and tissue destruction. The results of this study suggest that eicosanoids may be involved in the pathophysiology of spinal cord trauma through two potential mechanisms: 1) site specific increase in the TXB2/6-keto-PGF1 alpha ratio immediately following trauma which is due primarily to an increase in TXA2 synthesis; 2) the increase synthesis of 5-HETE which signals the activation of the 5-lipoxygenase pathway of arachidonate metabolism and production of mediators that are involved in inflammatory mechanisms and may affect local blood flow regulation and blood-spinal cord barrier integrity.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Culture Techniques; Dinoprostone; Edema; Hydroxyeicosatetraenoic Acids; Male; Prostaglandins E; Rabbits; Spinal Cord; Spinal Cord Injuries; Thromboxane B2

An increased accumulation of tissue thromboxane A2 occurred shortly after spinal cord injury. Prostacyclin formation was not affected. The magnitude of the increase in thromboxane and the extent of post-traumatic vascular damage as determined by extravasation of 125I-labeled human serum albumin were both dependent on the degree of injury. These findings raise the possibility that activation of arachidonic acid metabolism with a preponderance in thromboxane formation may contribute to microvascular injury in experimental spinal cord contusion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Vessels; Edema; Epoprostenol; Rats; Rats, Inbred Strains; Spinal Cord; Spinal Cord Injuries; Thromboxane A2; Thromboxane B2

We measured levels of thromboxane B2 and 6-keto-PGF1 alpha in rabbit spinal cord and cat CSF after impact injury to spinal cord. Rabbit tissue thromboxane B2 levels increased more than 6-keto-PGF1 alpha. In cat, CSF thromboxane B2 was higher the first hour postinjury; CSF 6-keto-PGF1 alpha also increased, but less so. These results imply activation of arachidonic acid metabolism. The relatively greater increase of thromboxane B2 suggests that thromboxane-prostacyclin imbalance may contribute to post-traumatic ischemia.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cats; Epoprostenol; Male; Rabbits; Spinal Cord Injuries; Thromboxane A2; Thromboxane B2; Thromboxanes