Normal pressure hydrocephalus decreases the proliferation of oligodendrocyte progenitor cells and the expression of CNPase and MOG proteins in the corpus callosum before behavioral deficits occur.

Tania Campos-Ordoñez, Susana González-Granero, Marielena Eudave-Patiño, Jonathan Buriticá, Vicente Herranz-Pérez, José M García-Verdugo, Oscar Gonzalez-Perez

Experimental neurology 2023 Jul

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Normal pressure hydrocephalus (NPH) compromises the morphology of the corpus callosum (CC). This study aims to determine whether 60- or 120-day NPH disrupts the cytoarchitecture and functioning of white matter (WM) and oligodendrocyte precursor cells (OPCs) and establish whether these changes are reversible after hydrocephalus treatment. NPH was induced in CD1 adult mice by inserting an obstructive lamina in the atrium of the aqueduct of Sylvius. Five groups were assembled: sham-operated controls (60 and 120 days), NPH groups (60 and 120 days), and the hydrocephalus-treated group (obstruction removal after 60-d hydrocephalus). We analyzed the cellular integrity of the CC by immunohistochemistry, TUNEL analysis, Western blot assays, and transmission electron microscopy (TEM). We found a reduction in the width of the CC at 60 and 120 days of NPH. TEM analysis demonstrated myelin abnormalities, degenerative changes in the WM, and an increase in the number of hyperdense (dark) axons that were associated with significant astrogliosis, and microglial reactivity. Hydrocephalus also caused a decrease in the expression of myelin-related proteins (MOG and CNPase) and reduced proliferation and population of OPCs, resulting in fewer mature oligodendrocytes. Hydrocephalus resolution only recovers the OPC proliferation and MOG protein density, but the rest of the WM abnormalities persisted. Interestingly, all these cellular and molecular anomalies occur in the absence of behavioral changes. The results suggest that NPH severely disrupts the myelin integrity and affects the OPC turnover in the CC. Remarkably, most of these deleterious events persist after hydrocephalus treatment, which suggests that a late treatment conveys irreversible changes in the WM of CC. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Tania Campos-Ordoñez, Susana González-Granero, Marielena Eudave-Patiño, Jonathan Buriticá, Vicente Herranz-Pérez, José M García-Verdugo, Oscar Gonzalez-Perez. Normal pressure hydrocephalus decreases the proliferation of oligodendrocyte progenitor cells and the expression of CNPase and MOG proteins in the corpus callosum before behavioral deficits occur. Experimental neurology. 2023 Jul;365:114412