Regional and temporal changes in prostaglandin E 2 and thromboxane B 2 concentrations after spinal cord injury

Resnick, Daniel K.; Nguyen, Peter H.; Cechvala, Catherine F.

doi:10.1016/s1529-9430(01)00130-9

Cited by 23 publications

(7 citation statements)

References 11 publications

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“… 45 , 46 Others reported that increased eicosanoids were persistent at least for 3 days (the longest time point studied) after SCI. 47 Furthermore, Demediuk et al reported that induced concentrations of free fatty acid quickly increased after SCI, peaked at 3 days, and remained significantly high at 7 days after SCI. 48 The induction profiles of these PLA 2 metabolites are similar to that of cPLA 2 after SCI in the present study.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Liu

Deng

Zhang

et al. 2014

Annals of Neurology

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ObjectiveThe objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI).MethodsA combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice.ResultsSCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI.InterpretationcPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.

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Section: Discussionmentioning

confidence: 99%

Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Liu

Deng

Zhang

et al. 2014

Annals of Neurology

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“…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 (Resnick et al 2001; Tonai et al 1999). Furthermore, LPC has been shown to act as a proinflammatory chemoattractant for macrophages (Lauber et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of sPLA₂ following spinal cord injury and a functional role for sPLA₂‐IIA in mediating oligodendrocyte death

Titsworth

Cheng

et al. 2009

Glia

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After the initial mechanical insult of spinal cord injury (SCI), secondary mediators propagate a massive loss of oligodendrocytes. We previously showed that following SCI both the total phospholipases activity and cytosolic PLA2-IVα protein expression increased. However, the expression of secreted isoforms of PLA2 (sPLA2) and their possible roles in oligodendrocyte death following SCI remains unclear. Here we report that mRNAs extracted 15 min, 4 hr, 1 day, or 1 month after cervical SCI show marked upregulation of sPLA2-IIA and IIE at 4 hr after injury. In contrast, SCI induced down regulation of sPLA2-X, and no change in sPLA2-IB, IIC, V, and XIIA expression. At the lesion site, sPLA2-IIA and IIE expression were localized to oligodendrocytes. Recombinant human sPLA2-IIA (0.01, 0.1, or 2 μM) induced a dose-dependent cytotoxicity in differentiated adult oligodendrocyte precursor cells but not primary astrocytes or Schwann cells in vitro. Most importantly, pretreatment with S3319, a sPLA2-IIA inhibitor, before a 30 min H2O2 injury (1 or 10 mM) significantly reduced oligodendrocyte cell death at 48 hr. Similarly, pretreatment with S3319 before injury with IL-1β and TNFα prevented cell death and loss of oligodendrocyte processes at 72 hr. Collectively, these findings suggest that sPLA2-IIA and IIE are increased following SCI, that increased sPLA2-IIA can be cytotoxic to oligodendrocytes, and that in vitro blockade of sPLA2 can create sparing of oligodendrocytes in two distinct injury models. Therefore sPLA2-IIA may be an important mediator of oligodendrocyte death and a novel target for therapeutic intervention following SCI.

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“…Among prostanoids, prostaglandin E 2 (PGE 2 ), the most abundant PG in the CNS, is believed to be involved in several pathological events, such as fever induction [49] and eliciting pain hypersensitivity [50]. Many studies have reported that elevated PGE 2 levels can be detected in the cerebrospinal fluid of patients with Alzheimer's disease (AD) [51], stroke [52], amyotrophic lateral sclerosis (ALS) [53], spinal cord injury [54], and brain trauma [55,56].…”

Section: Two Edges Of Prostanoids and Cyclooxygenase: Inflammation Anmentioning

confidence: 99%

Prostaglandins and Cyclooxygenases in Glial Cells During Brain Inflammation

Tzeng

Hsiao

Mak

2005

CDTIA

112

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Many brain disorders such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington, stroke, head trauma, and infection, are associated with inflammation that is involved in neuropathologenesis and hyperalgesis. Microglia and astrocytes act as immune cells in the inflamed brain. Both cell types, but especially microglia, are thought to contribute to the onset of inflammation in many brain diseases by producing deleterious proinflammatory mediators. Prostaglandins (PGs), which are critical mediators of physiologic processes and inflammation, are largely produced by activated microglia and reactive astrocytes during brain inflammation. These compounds are converted from arachnoidic acid (AA) by two isoforms of the cyclooxygenase (COX) enzyme, namely COX-1 and COX-2. In particular, the action of COX-2 and PGs in CNS inflammation has gained much attention recently. PGs have been found to act neuroprotectively by elevating intracellular cAMP levels in neurons. These molecules also function as anti-inflammatory molecules to reduce the production of nitric oxide and proinflammatory cytokines, and to increase the expression of anti-inflammatory cytokines. However, accumulating evidence also shows that COX inhibitors alleviate various types of brain damage via suppressing inflammatory reactions. Accordingly, the roles of two COX enzymes in mediating inflammation and anti-inflammation have recently been debated. We provide here a review of recent findings indicating that the reciprocal interaction of glial cell activation, COX enzymes and PGs mediates neurodegeneration and neuroprotection during brain inflammation. In addition, the mechanism by which PGs mediate signaling is discussed.

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Regional and temporal changes in prostaglandin E 2 and thromboxane B 2 concentrations after spinal cord injury

Cited by 23 publications

References 11 publications

Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Differential expression of sPLA₂ following spinal cord injury and a functional role for sPLA₂‐IIA in mediating oligodendrocyte death

Prostaglandins and Cyclooxygenases in Glial Cells During Brain Inflammation

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Regional and temporal changes in prostaglandin E 2 and thromboxane B 2 concentrations after spinal cord injury

Cited by 23 publications

References 11 publications

Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury

Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury

Differential expression of sPLA2 following spinal cord injury and a functional role for sPLA2‐IIA in mediating oligodendrocyte death

Prostaglandins and Cyclooxygenases in Glial Cells During Brain Inflammation

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Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Cytosolic phospholipase A₂ protein as a novel therapeutic target for spinal cord injury

Differential expression of sPLA₂ following spinal cord injury and a functional role for sPLA₂‐IIA in mediating oligodendrocyte death