Abstracts

Rationale: Expression and activity of urokinase-type plaminogen activator (uPA) is increased after brain injury suggesting that like in cancer tissue, also in post-injury brain uPA plays a role in tissue remodeling, including neurodegeneration, neurogenesis, and angiogenesis. Methods: To mimic hippocampal cellular alterations in human temporal lobe epilepsy, we injected kainic acid (KA) into the hippocampus of adult Wt and uPA-/- mice. Tissue was analyzed at 6 d or 20 d post-injury for neurodegeration, neurogenesis and angiogenesis using immunohistochemistry technique together with unbiased stereological analysis Results: Severity of ipsilateral pyramidal and hilar cell damage was similar in both genotypes at 6 d post-injury. At 20 d post-injury, uPA-/- mice had more severe loss of contralateral pyramidal (p<0.05) and hilar neurons (p<0.05) than Wt mice. At 20 d post-injury, also the number of double-cortin (DCX)-positive newly-born neurons was reduced in uPA-/- mice as compared to Wt (p<0.01). No difference was observed in granule cell dispersion or distribution of DCX positive neurons in the dentate gyrus. Finally, uPA deficiency did not affect total length of hippocampal blood vessels or vessel density.