Thromboxane and 5-HETE increase after experimental spinal cord injury in rabbits.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D000818:Animals; D046508:Culture Techniques; D015232:Dinoprostone; D004487:Edema / Q000134:cerebrospinal fluid; D006893:Hydroxyeicosatetraenoic Acids / Q000134:cerebrospinal fluid*; D008297:Male; D011458:Prostaglandins E / Q000134:cerebrospinal fluid; D011817:Rabbits; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid* / Q000473:pathology; D013929:Thromboxane B2 / Q000134:cerebrospinal fluid*
D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone