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• W1578183568 abstract "Summary Purpose: Cortical tubers are epileptogenic lesions in patients with tuberous sclerosis complex (TSC). Giant cells and dysplastic neurons are pathological hallmarks of cortical tubers. Severe astrogliosis, which is invariably present in tubers, has attracted much less attention. We hypothesize that the development of astrogliosis in cortical tubers constitutes a primary pathology of astrocytes and is directly related to TSC 1/2 mutations.. Methods: To begin to test this hypothesis, we performed immunohistochemical and electron microscopic analysis of brain tuber tissue resected from epileptic TSC patients. We compared alterations in tuber astrocytes to those found in other acute and chronic human epilepsy pathologies. Results: We found that astrogliosis in tubers is comprised of a mixture of “gliotic” and “reactive” astrocytes. The majority of tuber astrocytes are “gliotic” astrocytes that are morphologically and immunophenotypically similar to astrocytes in areas of gliosis in hippocampal sclerosis (HS). However, specific immunostaining features differentiate TSC gliosis from HS gliosis. “Reactive” tuber astrocytes are large‐sized, vimentin positive cells in the vicinity of giant cells that show activation of the mammalian target of rapamycin (mTOR) pathway, consistent with mutated TSC gene function . These cells resemble acutely reactive human astrocytes seen in tissue resected from depth electrode implantation patients. Oligodendrocytes and NG2 expressing glial cells do not have any detectable alterations within tubers. Conclusions: We conclude that astrocytes are the type of glial cell selectively impacted in cortical tuber pathology. We propose that tubers may be dynamic lesions, with progression of astrocytes over time from “reactive” to “gliotic.” Tuber astrogliosis in TSC may represent a genetic “model” of gliosis that is phenotypically similar to gliosis seen in acquired human pathologies." @default.
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• W1578183568 date "2008-01-22" @default.
• W1578183568 modified "2023-09-29" @default.
• W1578183568 title "Tuberous sclerosis: A primary pathology of astrocytes?" @default.
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• W1578183568 doi "https://doi.org/10.1111/j.1528-1167.2008.01493.x" @default.
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