Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent large-scale molecular profiling study revealed a sevenfold upregulation in the expression of urokinase-type plasminogen activator (uPA) during epileptogenesis. uPA is a member of the plasminogen activation system, which is a major contributor to the reorganization of neuronal circuits after trauma. Here, we investigated the expression and activity of uPA in normal and epileptogenic rat hippocampus to test a hypothesis that the expression of uPA is altered in brain areas that undergo epilepsy-related circuitry reorganization. Epileptogenesis was triggered by inducing status epilepticus (SE) with electrical stimulation of the amygdala in rats. Continuous video-electroencephalogram recordings were used to monitor the development of SE and the occurrence of spontaneous seizures. Animals were killed at 1, 4 or 14 days after SE, and brains were processed for immunohistochemistry or protein extraction. Confocal microscopy analysis of double-immunolabelled preparations indicated that SE triggered an increased expression of uPA in hippocampal astrocytes, neurons, white matter and blood vessels. Zymography revealed that the expression of uPA protein is associated with increased levels of enzymatically active uPA during epileptogenesis. uPA expression and enzymatic activity peaked within 1-4 days after SE, that is, before the occurrence of spontaneous seizures, and remained elevated for at least 2 weeks. These data suggest that uPA is involved in the reorganization of neuronal tissue during the epileptogenic process.
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PMID:Increased expression and activity of urokinase-type plasminogen activator during epileptogenesis. 1704 Apr 80

Expression of urokinase-type plasminogen activator (uPA) is increased after brain injury, suggesting that, like in cancer tissue, uPA plays roles in brain remodeling. Here we injured brain with intrahippocampal kainic acid (KA) injection in adult Wt and uPA-/- mice. At 20 days post-injury, uPA-/- mice had more severe loss of contralateral pyramidal (p<0.05) and hilar neurons (p<0.05) than Wt mice. The number of doublecortin (DCX)-positive newly born neurons was also 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. uPA deficiency did not affect the total length of hippocampal blood vessels or vessel density. No differences were observed in the severity of status epilepticus or consequent epilepsy between the genotypes. These data indicate that uPA deficiency can unfavorably modulate both delayed neurodegeneration and neurogenesis but has little effect on post-injury neuronal migration and vascular density. Our results favor the idea that elevated uPA during the post-injury phase is neuroprotective.
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PMID:Urokinase-type plasminogen activator regulates neurodegeneration and neurogenesis but not vascular changes in the mouse hippocampus after status epilepticus. 2002 72

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.
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PMID:Epileptogenesis after traumatic brain injury in Plau-deficient mice. 2625 97