title: Epileptogenesis after traumatic brain injury in Plau-deficient mice.
abstract: Several components of the urokinase-type plasminogen activator receptor (uPAR)-interactome, including uPAR and its ligand sushi-repeat protein 2, X-linked (SRPX2), are linked to susceptibility to epileptogenesis in animal models and/or humans. Recent evidence indicates that urokinase-type plasminogen activator (uPA), a uPAR ligand with focal proteinase activity in the extracellular matrix, contributes to recovery-enhancing brain plasticity after various epileptogenic insults such as traumatic brain injury (TBI) and status epilepticus. Here, we examined whether deficiency of the uPA-encoding gene Plau augments epileptogenesis after TBI. Traumatic brain injury was induced by controlled cortical impact in the somatosensory cortex of adult male wild-type and Plau-deficient mice. Development of epilepsy and seizure susceptibility were assessed with a 3-week continuous video-electroencephalography monitoring and a pentylenetetrazol test, respectively. Traumatic brain injury-induced cortical or hippocampal pathology did not differ between genotypes. The pentylenetetrazol test revealed increased seizure susceptibility after TBI (p<0.05) in injured mice. Epileptogenesis was not exacerbated, however, in Plau-deficient mice. Taken together, Plau deficiency did not worsen controlled cortical impact-induced brain pathology or epileptogenesis caused by TBI when assessed at chronic timepoints. These data expand previous observations on Plau deficiency in models of status epilepticus and suggest that inhibition of focal extracellular proteinase activity resulting from uPA-uPAR interactions does not modify epileptogenesis after TBI.
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Tamuna
authors.initials: T
authors.lastname: Bolkvadze
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantala
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Puhakka
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Pedro
authors.initials: P
authors.lastname: Andrade
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. Electronic address: asla.pitkanen@uef.fi.
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkänen
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000201:enzymology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004827:Epilepsy / Q000201:enzymology* / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency* / Q000502:physiology*
chemical_list: D014568:Urokinase-Type Plasminogen Activator
keywords: Controlled cortical impact; Disease-modification; Epilepsy; Epileptiform discharge; Extracellular matrix; Pentylenetetrazol; Seizure susceptibility; Traumatic brain injury