Neuroscience, 2010-05, Vol.167 (3), p.929-945
2010
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- Autor(en) / Beteiligte
- Titel
- Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies
- Ist Teil von
- Neuroscience, 2010-05, Vol.167 (3), p.929-945
- Ort / Verlag
- Amsterdam: Elsevier
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of epilepsy and tPA has been implicated in the mechanisms underlying seizure activity. We investigated the expression and the cellular distribution of tPA and uPA in several epileptogenic pathologies, including hippocampal sclerosis (HS; n =6), and developmental glioneuronal lesions, such as focal cortical dysplasia (FCD, n =6), cortical tubers in patients with the tuberous sclerosis complex (TSC; n =6) and in gangliogliomas (GG; n =6), using immuno-cytochemical, western blot and real-time quantitative PCR analysis. TPA and uPA immunostaining showed increased expression within the epileptogenic lesions compared to control specimens in both glial and neuronal cells (hippocampal neurons in HS and dysplastic neurons in FCD, TSC and GG specimens). Confocal laser scanning microscopy confirmed expression of both proteins in astrocytes and microglia, as well as in microvascular endothelium. Immunoblot demonstrated also up-regulation of the uPA receptor (uPAR; P <0.05). Increased expression of tPA, uPA, uPAR and tissue PA inhibitor type mRNA levels was also detected by PCR analysis in different epileptogenic pathologies ( P <0.05). Our data support the role of PA system components in different human focal epileptogenic pathologies, which may critically influence neuronal activity, inflammatory response, as well as contributing to the complex remodeling of the neuronal networks occurring in epileptogenic lesions.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0306-4522eISSN: 1873-7544DOI: 10.1016/j.neuroscience.2010.02.047Titel-ID: cdi_proquest_miscellaneous_746150166
- Format
- –
- Schlagworte
- Adolescent, Adult, Astrocytes - metabolism, Biological and medical sciences, Biomarkers - metabolism, Blotting, Western, Brain - abnormalities, Brain - metabolism, Brain - pathology, Brain Neoplasms - complications, Brain Neoplasms - metabolism, Brain Neoplasms - physiopathology, Child, Epilepsy - etiology, Epilepsy - metabolism, Epilepsy - physiopathology, Female, Fundamental and applied biological sciences. Psychology, Ganglioglioma - complications, Ganglioglioma - metabolism, Ganglioglioma - physiopathology, Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy, Hippocampus - metabolism, Hippocampus - pathology, Hippocampus - physiopathology, Humans, Immunohistochemistry, Male, Malformations of Cortical Development - complications, Malformations of Cortical Development - metabolism, Malformations of Cortical Development - physiopathology, Medical sciences, Microglia - metabolism, Middle Aged, Nervous system (semeiology, syndromes), Nervous System Malformations - complications, Nervous System Malformations - metabolism, Nervous System Malformations - physiopathology, Neurology, Receptors, Urokinase Plasminogen Activator - metabolism, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - metabolism, Tissue Plasminogen Activator - analysis, Tissue Plasminogen Activator - genetics, Tissue Plasminogen Activator - metabolism, Tuberous Sclerosis - complications, Tuberous Sclerosis - metabolism, Tuberous Sclerosis - physiopathology, Urokinase-Type Plasminogen Activator - analysis, Urokinase-Type Plasminogen Activator - genetics, Urokinase-Type Plasminogen Activator - metabolism, Vertebrates: nervous system and sense organs, Young Adult