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• W2022028909 abstract "Abstract Degeneration or survival of cerebral tissue after ischemic injury depends on the source, intensity, and duration of the insult. In the model of focal ischemia, reduced blood flow results in a cascade of pathophysiologic events, including inflammation, excitotoxicity, and platelet activation at the site of injury. One serine protease that is associated closely with and produced in response to central nervous system (CNS) injury is thrombin. Thrombin enters the injury cascade in brain either via a compromised blood‐brain barrier or possibly from endogenous prothrombin. Thrombin mediates its action through the protease‐activated receptor family (PAR‐1, ‐3, and ‐4). PARs belong to the superfamily of G protein‐coupled receptors with a 7‐transmembrane domain structure and are activated by proteolytic cleavage of their N‐terminus. We showed that thrombin can be neuroprotective or deleterious when present at different concentrations before and during oxygen‐glucose deprivation, an in vitro model of ischemia. We examined the change in mRNA expression levels of PAR‐1 to 4 as a result of transient focal ischemia in rat brain, induced by microinjection of endothelin near the middle cerebral artery. Using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR) analysis, after ischemic insult on the ipsilesional side, PAR‐1 was found to be downregulated significantly, whereas PAR‐2 mRNA levels decreased only moderately. PAR‐3 was upregulated transiently and then downregulated, and PAR‐4 mRNA levels showed the most striking (2.5‐fold) increase 12 hr after ischemia, in the injured side. In the contralateral hemisphere, mRNA expression was also affected, where decreased mRNA levels were observed for PAR‐1, ‐2, and –3, whereas PAR‐4 levels were reduced only after 7 days. Taken together, these data suggest involvement of the thrombin receptors PAR‐1, PAR‐3, and PAR‐4 in the pathophysiology of brain ischemia. © 2003 Wiley‐Liss, Inc." @default.
• W2022028909 created "2016-06-24" @default.
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• W2022028909 date "2003-11-24" @default.
• W2022028909 modified "2023-10-18" @default.
• W2022028909 title "Transient focal ischemia in rat brain differentially regulates mRNA expression of protease‐activated receptors 1 to 4" @default.
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• W2022028909 doi "https://doi.org/10.1002/jnr.10847" @default.
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