In acute stage of @entity385 , the surrounding zone of fresh @entity1188 is termed penumbra, where microglia are activated in response to damaged cell-derived proinflammatory mediators. Rescuing penumbra by regulating inflammatory activity would minimize @entity1188 volume, which positively correlates with functional outcome. To elucidate mechanisms by which inflammation occurs in penumbra, we performed immunohistochemical investigations using autopsied @entity1 brains affected by acute, subacute and chronic stages of @entity385 as well as cell culture experiments using a @entity19 microglia-derived cell line (BV-2). In penumbra of fresh @entity1188 , immunoreactivity for @entity35011 ( @entity35011 ), which is responsible for the production and release of the proinflammatory mediator @entity6579 ( @entity15002 ), was intensely detected in neurons and astrocytes. Furthermore, immunoreactivities for the LPC receptors G protein-coupled receptor 132 ( @entity47112 ) and P2X purinoreceptor 7 (P2X7R), as well as the CC chemokine monocyte chemoattractant protein-1 ( @entity2842 ) and its receptor @entity9172 , were detectable in activated microglia. Prior to cell culture experiments, it was confirmed that BV-2 cells were immunoreactive for ionized @entity141 -binding adaptor molecule 1 ( @entity11654 ), @entity47112 , P2X7R, @entity2842 and @entity9172 . Reverse transcription-quantitative polymerase chain reaction analysis revealed that @entity2842 and @entity9172 mRNA expression levels were significantly increased by LPC stimulation. The LPC-driven increase in @entity2842 transcripts was lowered by blockade of @entity47112 or P2X7R or by inhibition of Rho-associated protein kinase (ROCK) or inhibitor of kBa kinase. The LPC-driven increase in @entity9172 transcripts was lowered by blockade of @entity47112 or P2X7R or by inhibition of ROCK, phosphatidylinositide 3-kinanse, extracellular signal-regulated kinase kinase, or @entity1435 mitogen-activated protein kinase. The present results provide in vivo and in vitro evidence that in acute stage of @entity385 , the @entity35011 enzyme product LPC is released from neurons and astrocytes and stimulates penumbra microglia via @entity47112 and P2X7R, thereby exerting the @entity2842 / @entity9172 -mediated @entity2359 through distinct cell-signaling pathways.

Activated microglia in XXXX penumbra upregulate @entity2842 and @entity9172 expression in response to @entity6579 derived from adjacent neurons and astrocytes.

@entity1 :: ('9606', 'Species') :: ['human'] @entity6579 :: ('MESH:D008244', 'Chemical') :: ['lysophosphatidylcholine'] @entity35011 :: ('8399', 'Gene') :: ['secretory phospholipase A2 group X', 'sPLA2 -X'] @entity47112 :: ('c|SUB|G|2|A', 'DNAMutation') :: ['G2A'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity9172 :: ('729230', 'Gene') :: ['CCR2'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity2842 :: ('6347', 'Gene') :: ['MCP-1'] @entity11654 :: ('199', 'Gene') :: ['Iba1'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarcts', 'infarct'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity15002 :: ('CHEBI:16728', 'Chemical') :: ['LPC'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity'] @entity385 :: ('MESH:D002544', 'Disease') :: ['ischemic stroke', 'cerebral infarction']
@entity385 :: (MESH:D002544,Disease) :: ['ischemic stroke']
