Brain pathology
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Ganglioglioma (GG) is a grade I tumor characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As co-occurrence of H3 K27M and BRAF V600E mutations has been reported in midline tumors and anaplastic GG, we searched for BRAF V600E and H3 K27M mutations in a series of 54 paediatric midline grade I GG (midline GG) to determine the frequency of double mutations and its relevance for prognosis. ⋯ We demonstrate in this first series of midline GGs that the H3 K27M mutation can occur in association with the BRAF V600E mutation in grade I glioneuronal tumors. Despite the presence of H3 K27M mutations, these cases should not be graded and treated as grade IV tumors because they have a better spontaneous outcome than classic diffuse midline H3 K27M-mutant glioma. These data suggest that H3 K27M cannot be considered a specific hallmark of grade IV diffuse gliomas and highlight the importance of integrated histomolecular diagnosis in paediatric brain tumors.
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Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of SOD1(G93A) ALS mice.
Nowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioral abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS. ⋯ Finally, co-localization studies revealed expression of NLRP3, ASC and IL1β in neurons. Our study yielded two main findings: (i) neurodegenerative changes already occur at an early symptomatic stage in the AD and (ii) increased inflammasome expression may contribute to neuronal cell death. In conclusion, neurodegeneration in the anterior thalamus may critically account for cognitive changes in ALS pathology.
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Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO. ⋯ NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.
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Although BMP4-induced differentiation of glioma stem cells (GSCs) is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study, we established several GSC-enriched cell lines (GSC-ECLs) from high-grade gliomas. The expansion of these cells as adherent monolayers, and not as floating neurospheres, enabled a thorough study of the phenotypic changes that occurred during their differentiation. ⋯ Additionally, treatment of GSC-ECLs with the BMP antagonist, Noggin, also led to evident phenotypic changes. Interestingly, under certain conditions, some GSC-ECLs adopted an unexpected smooth muscle-like phenotype. As a whole, our findings illustrate the wide differentiation potential of GSCs, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies.
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Review
Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus.
History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. ⋯ It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (eg, interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes.