Expression of the plasminogen activator system and the inhibitors PAI-1 and PAI-2 in posttraumatic lesions of the CNS and brain injuries following dramatic circulatory arrests: An immunohistochemical study

Plasminogen activators as inducible extracellular serine proteases are invo lved in a variety of processes, such as the degradation of brain structures . In regions of brain degradation, an increase in the expression of genes e ncoding cytokines and proteinases has recently been demonstrated. We tested the hypothesis, whether the plasminogen activator system as well as the pl asminogen activator inhibitors are expressed and possibly involved in a pro teolytic cascade that breaks down the extracellular matrix as a result of i schemic or posttraumatic brain destructions. To study this supposition, we investigated immunohistochemically the expression of tPA, uPA and its recep tor, the plasminogen activator inhibitors PAI-1 and PAI-2, tetranectin as w ell as the laminin breakdown as an event of secondary brain injury. Brain t issue from 21 autopsy cases with severe brain injuries, material from 14 is chemic infarcts and 11 controls with acute hypoxia were used. All component s of the plasminogen activator system studied were overexpressed immunohist ochemically in reactive astrocytes, microglia and endothelial cells around the lesion zone. Tetranectin showed an analogous distribution to the plasmi nogen activator system. A reduced immunoreactivity of laminin within the id entical region of destruction was detected concomitant with laminin remnant s in perivascular macrophages, so that a remarkable role of the plasmin cas cade in the degradation of extracellular matrix proteins in the brain is ta ken into consideration.