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      Pío del Río Ortega: A Pioneer in the Pathology of Central Nervous System Tumors

      review-article
      Frontiers in Neuroanatomy
      Frontiers Media S.A.
      histogenesis, gliomas, Rio Hortega, brain tumors, classification

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          Abstract

          The last 140 years have seen considerable advances in knowledge of central nervous system tumors. However, the main tumor types had already been described during the early years of the twentieth century. The studies of Dr. Pío del Río Hortega have been ones of the most exhaustive histology and cytology-based studies of nervous system tumors. Río Hortega's work was performed using silver staining methods, which require a high level of practical skill and were therefore difficult to standardize. His technical aptitude and interest in nervous system tumors played a key role in the establishment of his classification, which was based on cell lineage and embryonic development. Río Hortega's approach was controversial when he proposed it. Current classifications are not only based on cell type and embryonic lineage, as well as on clinical characteristics, anatomical site, and age.

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          From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

          Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called “third element” of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely “resting,” and their contribution as “activated” cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: “resting” microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.
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            Pío del Río Hortega and the discovery of the oligodendrocytes

            Pío del Río Hortega (1882–1945) discovered microglia and oligodendrocytes (OLGs), and after Ramón y Cajal, was the most prominent figure of the Spanish school of neurology. He began his scientific career with Nicolás Achúcarro from whom he learned the use of metallic impregnation techniques suitable to study non-neuronal cells. Later on, he joined Cajal’s laboratory. and Subsequently, he created his own group, where he continued to develop other innovative modifications of silver staining methods that revolutionized the study of glial cells a century ago. He was also interested in neuropathology and became a leading authority on Central Nervous System (CNS) tumors. In parallel to this clinical activity, del Río Hortega rendered the first systematic description of a major polymorphism present in a subtype of macroglial cells that he named as oligodendroglia and later OLGs. He established their ectodermal origin and suggested that they built the myelin sheath of CNS axons, just as Schwann cells did in the periphery. Notably, he also suggested the trophic role of OLGs for neuronal functionality, an idea that has been substantiated in the last few years. Del Río Hortega became internationally recognized and established an important neurohistological school with outstanding pupils from Spain and abroad, which nearly disappeared after his exile due to the Spanish civil war. Yet, the difficulty of metal impregnation methods and their variability in results, delayed for some decades the confirmation of his great insights into oligodendrocyte biology until the development of electron microscopy and immunohistochemistry. This review aims at summarizing the pioneer and essential contributions of del Río Hortega to the current knowledge of oligodendrocyte structure and function, and to provide a hint of the scientific personality of this extraordinary and insufficiently recognized man.
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              A study of tumors arising from ependymal cells.

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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/130071/overview
                Journal
                Front Neuroanat
                Front Neuroanat
                Front. Neuroanat.
                Frontiers in Neuroanatomy
                Frontiers Media S.A.
                1662-5129
                01 March 2016
                2016
                : 10
                : 13
                Affiliations
                Pathology Department, Vall d'Hebron University Hospital, Universidad Autónoma of Barcelona Barcelona, Spain
                Author notes

                Edited by: Fernando De Castro, Instituto Cajal-CSIC and Hospital Nacional de Parapléjicos, Spain

                Reviewed by: Isidro Ferrer, University of Barcelona, Spain; Antonio Di Ieva, Macquarie University Hospital, Australia

                *Correspondence: Santiago Ramon y Cajal Agüeras sramonycajal@ 123456gmail.com
                Article
                10.3389/fnana.2016.00013
                4771935
                26973470
                76c418e7-7237-4415-99d5-feae597782a3
                Copyright © 2016 Ramon y Cajal Agüeras.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 December 2015
                : 04 February 2016
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 55, Pages: 8, Words: 4881
                Funding
                Funded by: Ministerio de Economía y Competitividad 10.13039/501100003329
                Award ID: 11/00185
                Award ID: RD06/0020/1020
                Categories
                Neuroscience
                Review

                Neurosciences
                histogenesis,gliomas,rio hortega,brain tumors,classification
                Neurosciences
                histogenesis, gliomas, rio hortega, brain tumors, classification

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