738 Biphasic Elevation of Prostaglandin E2 and Thromboxane B2 Concentrations after Spinal Cord Injury

Inhibition of Cytosolic Phospholipase A2Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury

“…after SCI 51 . In addition, concentrations of free fatty acid quickly increased after SCI, peaked at 3 d, and remained significantly high at 7 d after SCI 52 .…”

Role of phospholipase A2s and lipid mediators in secondary damage after spinal cord injury

“…Treatment with selective COX-2 inhibitors has been shown to improve locomotor recovery in mild to moderate types of contusion injuries (Resnick et al 1998;Hains et al 2001) and photochemical SCI in rats (López-Vales et al 2006) but not in more severe contusion lesions (Resnick et al 1998). PGE 2 and TXB 2 , a stable metabolite of TXA 2 , have been found to be significantly increased over the first 72 h in the injured spinal cord (Resnick et al 2001a), indicating that COX-2 is metabolically active after SCI. COX-2 inhibition reduces this increase in PGE 2 and TXB 2 by three-to four-fold at 4 h and 24 h after SCI (Resnick et al 2001b).…”

“…This neurotoxicity is primarily mediated by increased intracellular Ca 2+ . PGE 2 has been found to be significantly increased in the spinal cord over the first 72 h after injury (Resnick et al 2001a), but no studies have directly examined its role in SCI. We have reported recently that, in a spinal cord contusion injury, the beneficial effects of a weak pan-PLA 2 inhibitor (AX115) appears to be mediated via the EP1 receptor , as AX115 treatment induces an increase in EP1 expression in the injured spinal cord, and as the beneficial effect of AX115 on locomotor recovery is abrogated by treatment with the EP1 antagonist (SC51089).…”

A possible role for sPLA2 in oligodendrocyte death and spinal cord injury.

“…Bioactive eicosanoids, derived from PLA 2 -induceds production of AA, have been implicated as mediators of secondary injury via a host of mechanisms. The expression of eicosanoids, such as TXA 2 and PGE 2 increased in the injured cord tissue within hours of SCI and their vasoactive properties are thought to create microemboli in addition to PGE 2 's well known pro-inflammatory effects (Tonai et al, 1999, Resnick et al, 2001. Increased production of TXA 2 , PGI 2 , LTC 4 and 5-HETE has also been confirmed in experimental SCI (Jacobs et al, 1987, Mitsuhashi et al, 1994.…”

“…AA can later form epoxides via the cytochrome P450 pathway, leukotrienes via the lipoxygenase pathway, or thromboxanes or prostaglandins via the cyclooxygenase pathway. Many of these products, such as prostaglandin E 2 (PGE 2 ), can subsequently act as potent chemoattractants that increase the endogenous immune response (Tonai et al, 1999, Resnick et al, 2001). Furthermore, LPC has been shown to transiently demyelinate both the central and peripheral nervous system (Blakemore et al, 1977) and act as a proinflammatory chemoattractant for macrophages (Lauber et al, 2003 (Blakemore et al, 1977) and has been shown to be a chemoattractant as well (Lauber et al, 2003).…”