Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia

A variety of extracellular serine proteases are expressed in the central ne rvous system or might permeate the blood-brain barrier under pathological c onditions. However, their intracerebral targets and physiological functions are largely unknown. Here, we show that four distinct subtypes of protease -activated receptors (PARs) are abundantly expressed in the adult rat brain and in organotypic hippocampal slice cultures. PAR-1 expression was signif icant in the hippocampus, cortex and amygdala. Highest densities of PAR-2 a nd PAR-3 were observed in hippocampus, cortex, amygdala, thalamus, hypothal amus and striatum. Apart from the striatum, a similar localization was foun d for PAR-4. Within the hippocampal formation, each PAR subtype was predomi nantly localized in the pyramidal cell layers. Additionally, we identified PAR-2 in mossy fibers between dentate gyrus and CA3, PAR-3 in the subiculum and PAR-4 in CA3 and in mossy fibres as well as in the stratum lacunosum m oleculare. After exposing hippocampal slice cultures to a severe experiment al ischemia (oxygen-glucose deprivation), the expression of PARs 1-3 was up -regulated with subtype-specific kinetics. The localization of PARs in brai n regions particularly vulnerable to ischemic insults as well as distinct a lterations in the expression pattern after experimental ischemia support th e notion of an important role of extracellular serine proteases and PARs in cerebral ischemia.