Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome
| Autor: | Benoît Balau, Luc Poncelet, Bruno Couturier, Fabrice Gankam-Kengne, Kathleen De Swert, Joanna Bouchat, Charles Nicaise, Jean Pierre Brion, Jacques Gilloteaux, Catherine Marneffe |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty mice CNS demyelination Central nervous system microglia Biology blood–brain barrier Blood–brain barrier Capillary Permeability Necrosis 03 medical and health sciences Cellular and Molecular Neuroscience Myelin astrocyte 0302 clinical medicine Neurologie Forelimb Evoked Potentials Auditory Brain Stem medicine Animals Muscle Strength Microglia Brain Gap Junctions Oligodendrocyte Mice Inbred C57BL Disease Models Animal Oligodendroglia 030104 developmental biology medicine.anatomical_structure Neurology Astrocytes Connexin 43 Disease Progression Brainstem Sciences cognitives osmotic demyelination syndrome oligodendrocyte 030217 neurology & neurosurgery Demyelinating Diseases Astrocyte |
| Zdroj: | GLIA, 66 (3 |
| ISSN: | 0894-1491 |
| DOI: | 10.1002/glia.23268 |
| Popis: | The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood–brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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