Deficiency of plasminogen activator inhibitor type 2 limits brain edema formation after traumatic brain injury.

Plasminogen activator inhibitor type 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 6h after traumatic brain injury (TBI) with a maximum increase of 87-fold at 12h. To investigate a potentially detrimental influence of PAI-2 on secondary posttraumatic processes, male PAI-2 deficient (PAI-2-KO) and wild-type mice (WT) were subjected to TBI by controlled cortical impact injury (CCI). 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 24h 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, ZO-1). In contrast to plasminogen activator inhibitor type 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 posttraumatic brain edema.