Abstract
Arachidonate metabolites have many kinds of bioactivities. Thromboxane A2(TXA2) stimulates platelet aggregation and vasoconstriction, whereas prostaglandin I2(PGI2) antagonises its activities. Thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) are determined in biological materials. Production of TXB2, 6-keto-PGF1αand leukotriene C4(LTC4), which have potent vascular permeability, was measured by radioimmunoassay in experimental spinal cord injured animals. TXB2level in the rat spinal cord reached a peak concentration of 133.6 ± 3.8 pmol/g cord, and 6-keto-PGFlfVincreased to 26.2 ± 11.7 pmol/g cord 5 minutes after the injury. There was good correlation between TXB2production and vascular damage as monitored by fluorescein uptake. When OKY-046 ((E)-3-[4-(1-imidazolylmetyl) phenyl]-2-propenoic acid), which selectively inhibits TXA2synthetase activity, was administered 10 minutes before injury, the increase in TXB2production was inhibited by more than 80%, but the degree of vascular damage was reduced by only 40%. In the guinea pig spinal cord, LTC4levels reached a peak concentration of 2.2 ± 0.4 pmol/g cord 10 minutes after compression, while that of TXB2reached 146.8 ± 6.2 pmol/g cord. The increased production of TXB2was correlated with the degree of compression injury while that of LTC4production did not. These findings suggest that vasoactive eicosanoids, TXA2, PGI2and LTC4, play important roles in secondary damage following spinal cord injury, although their roles may be different among species of animals.
Similar content being viewed by others
Article PDF
References
Jonsson H T, Daniell H B (1976) Altered levels of PGF in cat spinal cord tissue following traumatic injury. Prostaglandins 11: 51–59.
Hsu C Y, Halushka P V, Hogan E L et al (1985) Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury. Neurology 35: 1003–1009.
Hiraku S, Taniguchi K, Wakitani K et al (1986) Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[4-(l-imidazolylmetyl) phenyl]-2- propenoic acid (OKY-046). J Pharmacol 41: 393–401.
Ban M, Tonai T, Kohno T et al (1989) A flavonoid inhibitor of 5-lipoxygenase inhibits leukotriene production following ischemia in gerbil brain. Stroke 20: 248–252.
Demopoulos H B, Flamm E S, Pietronigro D D, Seligman M L (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta Physiol Scand Suppl 492: 91–119.
Demediuk P, Faden A I (1988) Traumatic spinal cord injury in rats causes increases in tissue thromboxane but not peptidoleukotrienes. J Neurosci Res 20: 115–121.
Hsu C Y, Halushka P V, Hogan E L, Cox R D (1986) Increased thromboxane level in experimental spinal cord injury. J Neurol Sci 74: 289–296.
Black K L, Hoff J T (1985) Leukotrienes increase blood-brain barrier permeability following intraparenchy-mal injections in rats. Ann Neurol 18: 349–351.
Kiwak K J, Moskowitz M A, Levine L (1985) Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury. J Neurosurg 62: 865–869.
Faden A I, Lemke M, Demediuk P (1988) Effects of BW755C, a mixed cyclooxygenase-lipoxygenase inhibitor, following traumatic spinal cord injury in rats. Brain Res 463: 63–68.
Moreland D B, Soloniuk D S, Feldman M J (1989) Leukotrienes in experimental spinal cord injury. Surg Neurol 31: 277–280.
Xu J J, Hsu C Y, Liu T S et al (1990) Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury. J Neurochem 55: 907–912.
Saunders R D, Dugan L L, Demediuk P et al (1987) Effects of methylprednisolone and the combination of α-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J Neurochem 55: 24–31.
Yokota K, Tonai T, Horie K et al (1986) Enzyme immunoassay of prostanoids in human blood and urine. In: Hayaishi O, Yamamoto S, editors. Advances in Prostaglandin, Thromboxane Leukotriene Research. Vol 15. Raven Press, New York: 33–34.
Dempsey R J, Roy M W, Meyer K et al (1986) Development of cyclooxygenase and lipoxygenase metabolites of arachidonic acid after transient cerebral ischemia. J Neurosurg 64: 118–124.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mitsuhashi, T., Ikata, T., Morimoto, K. et al. Increased production of eicosanoids, TXA2, PGI2 and LTC4 in experimental spinal cord injuries. Spinal Cord 32, 524–530 (1994). https://doi.org/10.1038/sc.1994.84
Issue Date:
DOI: https://doi.org/10.1038/sc.1994.84
Keywords
This article is cited by
-
The effects of myelin on macrophage activation are phenotypic specific via cPLA2 in the context of spinal cord injury inflammation
Scientific Reports (2021)
-
Role of phospholipase A2s and lipid mediators in secondary damage after spinal cord injury
Cell and Tissue Research (2012)
-
Effects of zileuton and montelukast in mouse experimental spinal cord injury
British Journal of Pharmacology (2008)