Plasminogen activator inhibitor-2 (PAI-2/SerpinB2) inhibits extracellular urokinase plasminogen activator (uPA). Under physiological conditions, PAI-2 is expressed at low levels but is rapidly induced by inflammatory triggers. It is a negative regulator of fibrinolysis and serves to stabilize clots. In the present study, PAI-2 expression is upregulated 25-fold in pericontusional brain tissue at 6 h after traumatic brain injury (TBI), with a maximum increase of 87-fold at 12 h. To investigate a potentially detrimental influence of PAI-2 on secondary post-traumatic processes, male PAI-2–deficient (PAI-2-KO) and wild-type mice (WT) were subjected to TBI by controlled cortical impact injury. Brain lesion volume and cerebral inflammation were not different. Total brain volume was significantly smaller in PAI-2-KO, indicating reduced brain swelling. The brain water content at 24 h post-insult was significantly smaller in PAI-2-KO mice. Markers of vasogenic brain edema showed no difference in blood–brain barrier integrity and expression of blood–brain barrier proteins (claudin-5, zonula occludens-1). In contrast to plasminogen activator inhibitor-1 (PAI-1), PAI-2 plays a limited role for brain lesion formation and does not influence blood–brain barrier integrity. PAI-2 contributes to brain edema formation and could therefore be a promising new target to treat post-traumatic brain edema.
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