Plau/Plaur double-deficiency did not worsen lesion severity or vascular integrity after traumatic brain injury

Abstract

Binding of urokinase-type plasminogen activator receptor (uPAR) to its ligand uPA or to its plasma membrane partner, platelet-derived growth factor receptor β (PDGFRβ), promotes neuroprotection, cell proliferation, and angiogenesis. Following injury, single deficiency in uPA or uPAR leads in increased tissue loss and compromised vascular remodeling. We hypothesized that double-deficiency of uPAR (Plaur) and uPA (Plau) would result in increased lesion area and poor vascular integrity after traumatic brain injury (TBI). TBI was induced by lateral fluid-percussion injury in Plau/Plaur double-knockout (dKO) and wild-type (Wt) mice. The cortical lesion area was quantified in unfolded cortical maps prepared from thionin-stained sections at 4 d or 30 d post-TBI. The density of PDGFRβ+ pericytes and blood vessels was calculated from immunostained sections. Blood-brain barrier leakage was analyzed using ImageJ® from IgG-immunostained sections. Genotype had no effect on the total area of the cortical lesion at 4 d or 30 d post-TBI (p > 0.05) or its progression as the overall lesion area was comparable at 4 d and 30 d post-TBI in both genotypes (p > 0.05). Subfield analysis, however, indicated that damage to the visual cortex at 4 d post-TBI in dKO-TBI mice was 53 % of that in Wt-TBI mice (p < 0.05). Both genotypes had a higher density of PDGFRβ-positive pericytes at 4 d than at 30 d post-TBI (p < 0.05), but no genotype effect was detected between these time-points (p > 0.05). TBI-induced increase in the density of PDGFRβ+ blood vessels at the region adjacent to the lesion core was comparable in both genotypes (p > 0.05). Genotype had no effect on TBI-induced IgG leakage into the perilesional cortical parenchyma (p > 0.05). Contrary to our expectations, Plau/Plaur double-deficiency did not aggravate TBI-related structural outcome.