Cyclooxygenases (COX) are prostanoid synthesizing enzymes constitutively expressed in the brain that contribute to excitotoxic neuronal cell death. While the neurotoxic role of @entity10178 is well established and has been linked to @entity1421 synthesis, the role of @entity16538 is not clearly understood. In a model of @entity1024 ( @entity143 ) induced excitotoxicity in the @entity19 cerebral cortex we found a distinctive temporal profile of @entity16538 and @entity10178 activation where @entity16538 , located in microglia, is responsible for the early phase of @entity1421 synthesis (10 minutes after @entity143 ), while both @entity16538 and @entity10178 contribute to the second phase (3-24 hours after @entity143 ). Microglial @entity16538 is strongly activated by @entity855 but not excitatory neurotransmitters or the @entity1990 ligand bacterial lipopolysaccharide. @entity855 induced microglial @entity16538 dependent @entity1421 synthesis is dependent on @entity6200 receptors, extracellular @entity141 and cytoplasmic phospholipase A2. @entity143 receptor activation induces @entity855 release from cultured neurons leading to microglial @entity6200 activation and @entity16538 dependent @entity1421 synthesis in mixed @entity528 . Pharmacological inhibition of @entity16538 has no effect on the @entity75 produced by @entity143 , but counteracts the neuroprotection exerted by inhibition of @entity10178 or observed in @entity19 lacking the prostaglandin E(2) receptor type 1. Similarly, the neuroprotection exerted by the prostaglandin E(2) receptor type 2 agonist butaprost is not observed after @entity16538 inhibition. @entity6200 receptors contribute to @entity143 induced @entity1421 production in vivo and blockage of @entity6200 receptors reverses the neuroprotection offered by @entity10178 inhibition. These findings suggest that purinergic signaling in microglia triggered by neuronal @entity855 modulates excitotoxic @entity75 by regulating @entity16538 dependent prostanoid production and unveil a previously unrecognized protective role of microglial @entity16538 in excitotoxic @entity1545 .

Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic XXXX .

@entity1545 :: ('MESH:D020214', 'Disease') :: ['brain injury'] @entity10178 :: ('17709(Tax:10090)', 'Gene') :: ['COX-2'] @entity16538 :: ('17708(Tax:10090)', 'Gene') :: ['COX-1'] @entity1024 :: ('CHEBI:31882', 'Chemical') :: ['N-Methyl-D-aspartic acid'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1421 :: ('MESH:D015232', 'Chemical') :: ['prostaglandin E(2)'] @entity75 :: ('MESH:D001927', 'Disease') :: ['cortical lesion'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1990 :: ('21898(Tax:10090)', 'Gene') :: ['Toll-like receptor 4'] @entity6200 :: ('18439(Tax:10090)', 'Gene') :: ['P2X7 receptor', 'P2X7'] @entity528 :: ('MESH:D009410', 'Disease') :: ['microglial-neuronal cultures'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity1545 :: (MESH:D020214,Disease) :: ['brain injury']
