Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy
Background: The Notch signaling pathway is an important regulator of stem cell activity in various tissues, including the central nervous system. It has been implicated in neurodevelopmental processes, including neuronal differentiation and synaptic plasticity. Research suggests that its expression...
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MDPI AG
2025-02-01
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| author | Dimitar Metodiev Petia Dimova Margarita Ruseva Dimitar Parvanov Rumiana Ganeva Georgi Stamenov Sevdalin Nachev Vesela Ivanova Rumen Marinov Krassimir Minkin |
| author_facet | Dimitar Metodiev Petia Dimova Margarita Ruseva Dimitar Parvanov Rumiana Ganeva Georgi Stamenov Sevdalin Nachev Vesela Ivanova Rumen Marinov Krassimir Minkin |
| author_sort | Dimitar Metodiev |
| collection | DOAJ |
| description | Background: The Notch signaling pathway is an important regulator of stem cell activity in various tissues, including the central nervous system. It has been implicated in neurodevelopmental processes, including neuronal differentiation and synaptic plasticity. Research suggests that its expression may be associated with certain epileptogenic lesions, particularly those with neurodevelopmental origin. The aim of this study was to investigate the expression of Notch-1 in brain biopsies from various cases of pharmacoresistant epilepsy. Methods: Here, we used immunohistochemistry staining to retrospectively analyze 128 developmental lesions associated with pharmacoresistant epilepsy, including 13 cases with focal cortical dysplasia (FCD) type I, 39 with FCD type II, 37 with hippocampal sclerosis (HS), 23 with FCD IIIc, 9 with mild malformations of cortical development (MCD), 4 cases with mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE), and 3 with tuberous sclerosis (TS). The tissues were stained for Neurofilament protein, Vimentin, S-100 protein, NeuN, and GFAP, as well as the stem cell marker Notch-1. Tissue that stained positively for Notch-1 was further characterized. Results: A positive Notch-1 reaction was found in all cases of FCD type IIb and TS, where it appeared in balloon cells but not in dysmorphic neurons, and in a single case of meningioangiomatosis (FCD IIIc), where it stained spider-like cells. Notch-1-positive cells showed a stem-like, glio-neuronal precursor immunophenotype. No staining was observed in the remaining cases with FCD type I, type III, HS, mild MCD, and MOGHE. Conclusions: Notch-1 displays a distinct pattern of expression in some epileptogenic lesions, potentially highlighting a stem cell-like origin or neurodevelopmental abnormalities contributing to pharmacoresistant epilepsy; however, it is not a general marker of such lesions. Its differential expression may prove useful in distinguishing between different types of FCD or other cortical malformations, which could assist in both their diagnosis and potentially in the development of more targeted therapeutic approaches. Further studies with different stem cell markers are needed in this direction. |
| format | Article |
| id | doaj-art-9191010f87d045a1826f2af4f862b28f |
| institution | DOAJ |
| issn | 2571-6980 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-9191010f87d045a1826f2af4f862b28f2025-08-20T02:42:28ZengMDPI AGNeuroglia2571-69802025-02-0161710.3390/neuroglia6010007Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant EpilepsyDimitar Metodiev0Petia Dimova1Margarita Ruseva2Dimitar Parvanov3Rumiana Ganeva4Georgi Stamenov5Sevdalin Nachev6Vesela Ivanova7Rumen Marinov8Krassimir Minkin9Neuropathological Laboratory, University Hospital “Saint Ivan Rilski”, 1431 Sofia, BulgariaEpilepsy Surgery Center, University Hospital “Saint Ivan Rilski”, 1431 Sofia, BulgariaDepartment of Research, Nadezhda Women’s Health Hospital, 1373 Sofia, BulgariaDepartment of Research, Nadezhda Women’s Health Hospital, 1373 Sofia, BulgariaDepartment of Research, Nadezhda Women’s Health Hospital, 1373 Sofia, BulgariaDepartment of Research, Nadezhda Women’s Health Hospital, 1373 Sofia, BulgariaNeuropathological Laboratory, University Hospital “Saint Ivan Rilski”, 1431 Sofia, BulgariaDepartment of General and Clinical Pathology, Faculty of Medicine, Medical University, 1431 Sofia, BulgariaDepartment of Cardiology, Nadezhda Women’s Health Hospital, 1373 Sofia, BulgariaEpilepsy Surgery Center, University Hospital “Saint Ivan Rilski”, 1431 Sofia, BulgariaBackground: The Notch signaling pathway is an important regulator of stem cell activity in various tissues, including the central nervous system. It has been implicated in neurodevelopmental processes, including neuronal differentiation and synaptic plasticity. Research suggests that its expression may be associated with certain epileptogenic lesions, particularly those with neurodevelopmental origin. The aim of this study was to investigate the expression of Notch-1 in brain biopsies from various cases of pharmacoresistant epilepsy. Methods: Here, we used immunohistochemistry staining to retrospectively analyze 128 developmental lesions associated with pharmacoresistant epilepsy, including 13 cases with focal cortical dysplasia (FCD) type I, 39 with FCD type II, 37 with hippocampal sclerosis (HS), 23 with FCD IIIc, 9 with mild malformations of cortical development (MCD), 4 cases with mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE), and 3 with tuberous sclerosis (TS). The tissues were stained for Neurofilament protein, Vimentin, S-100 protein, NeuN, and GFAP, as well as the stem cell marker Notch-1. Tissue that stained positively for Notch-1 was further characterized. Results: A positive Notch-1 reaction was found in all cases of FCD type IIb and TS, where it appeared in balloon cells but not in dysmorphic neurons, and in a single case of meningioangiomatosis (FCD IIIc), where it stained spider-like cells. Notch-1-positive cells showed a stem-like, glio-neuronal precursor immunophenotype. No staining was observed in the remaining cases with FCD type I, type III, HS, mild MCD, and MOGHE. Conclusions: Notch-1 displays a distinct pattern of expression in some epileptogenic lesions, potentially highlighting a stem cell-like origin or neurodevelopmental abnormalities contributing to pharmacoresistant epilepsy; however, it is not a general marker of such lesions. Its differential expression may prove useful in distinguishing between different types of FCD or other cortical malformations, which could assist in both their diagnosis and potentially in the development of more targeted therapeutic approaches. Further studies with different stem cell markers are needed in this direction.https://www.mdpi.com/2571-6980/6/1/7balloon cellsdysmorphic neuronsfocal cortical dysplasiaNotch-1stem cell marker |
| spellingShingle | Dimitar Metodiev Petia Dimova Margarita Ruseva Dimitar Parvanov Rumiana Ganeva Georgi Stamenov Sevdalin Nachev Vesela Ivanova Rumen Marinov Krassimir Minkin Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy Neuroglia balloon cells dysmorphic neurons focal cortical dysplasia Notch-1 stem cell marker |
| title | Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy |
| title_full | Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy |
| title_fullStr | Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy |
| title_full_unstemmed | Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy |
| title_short | Notch-1 Immunopositivity in Brain Lesions Associated with Pharmacoresistant Epilepsy |
| title_sort | notch 1 immunopositivity in brain lesions associated with pharmacoresistant epilepsy |
| topic | balloon cells dysmorphic neurons focal cortical dysplasia Notch-1 stem cell marker |
| url | https://www.mdpi.com/2571-6980/6/1/7 |
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