Increased production of eicosanoids, TXA2, PGI2and LTC4in experimental spinal cord injuries

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.