Astrocytes and Epilepsy

Jacqueline A. Hubbard, Devin K. Binder

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128026243
• Topic: Medicine
• Subtopic: Physiology

Epilepsy is a devastating group of neurological disorders characterized by periodic and unpredictable seizure activity in the brain. There is a critical need for new drugs and approaches given than at least one-third of all epilepsy patients are not made free of seizures by existing medications and become "medically refractory". Much of epilepsy research has focused on neuronal therapeutic targets, but current antiepileptic drugs often cause severe cognitive, developmental, and behavioral side effects. Recent findings indicate a critical contribution of astrocytes, star-shaped glial cells in the brain, to neuronal and network excitability and seizure activity. Furthermore, many important cellular and molecular changes occur in astrocytes in epileptic tissue in both humans and animal models of epilepsy. The goal of Astrocytes and Epilepsy is to comprehensively review exciting findings linking changes in astrocytes to functional changes responsible for epilepsy for the first time in book format. These insights into astrocyte contribution to seizure susceptibility indicate that astrocytes may represent an important new therapeutic target in the control of epilepsy.

Astrocytes and Epilepsy includes background explanatory text on astrocyte morphology and physiology, epilepsy models and syndromes, and evidence from both human tissue studies and animal models linking functional changes in astrocytes to epilepsy. Beautifully labelled diagrams are presented and relevant figures from the literature are reproduced to elucidate key findings and concepts in this rapidly emerging field. Astrocytes and Epilepsy is written for neuroscientists, epilepsy researchers, astrocyte investigators as well as neurologists and other specialists caring for patients with epilepsy.

• Presents the first comprehensive book to synthesize historical and recent research on astrocytes and epilepsy into one coherent volume
• Provides a great resource on the field of astrocyte biology and astrocyte-neuron interactions
• Details potential therapeutic targets, including chapters on gap junctions, water and potassium channels, glutamate and adenosine metabolism, and inflammation

Chapter 1

History of Astrocytes

Abstract

In this introduction to the history of astrocytes, we (1) contextualize the evolution of the concept of neuroglia within the development of cell theory and the “neuron doctrine”; (2) explain how the concept of neuroglia arose and evolved; (3) provide an interesting overview of some of the investigators involved in defining the cell types in the central nervous system; (4) select the interaction of Wilder Penfield and Pío del Río-Hortega for a more in-depth historical vignette portraying a critical period during which glial cell types were being identified, described, and separated; and (5) briefly summarize further developments that presaged the modern era of neuroglioscience.

Keywords

Astrocyte; cell theory; history; microglia; neuroglia; neuron doctrine; oligodendrocytes

Outline

Overview 2

Neuron Doctrine 2

Purkinje and Valentin’s Kugeln 2

Scheiden, Schwann, and Cell Theory 3

Remak’s Remarkable Observation 4

The Neurohistology of Robert Bentley Todd 5

Wilhelm His’ Seminal Contributions 7

Fridtjof Nansen: The Renaissance Man 8

Auguste Forel: Neurohistology, Myrmecology, and Sexology 8

Rudolph Albert Von Kölliker: Neurohistologist and Cajal Champion 10

Waldeyer and the Neuronlehre (Neuron Doctrine) 11

Conclusion 12

Development of the Concept of Neuroglia 12

Rudolf Virchow 12

Other Investigators Develop More Detailed Images of Neuroglial Cells 15

Camillo Golgi 16

Naming of the “Astrocyte” 18

Santiago Ramón y Cajal and Glial Functions 18

Glial Alterations in Neurological Disease: Early Concepts 21

Wilder Penfield, Pío Del Río-Hortega, and Delineation of the “Third Element” 22

Penfield’s Idea to Go to Spain 24

Types of Neuroglia 26

Penfield’s Description of Oligodendroglia 27

Coming Together: The Fruit of Penfield’s Spanish Expedition 30

Beginning of the Modern Era 33

References 34

Overview

In this introduction to the history of astrocytes, we wish to accomplish the following goals: (1) contextualize the evolution of the concept of neuroglia within the development of cell theory and the “neuron doctrine”; (2) explain how the concept of neuroglia arose and evolved; (3) provide an interesting overview of some of the investigators involved in defining the cell types in the central nervous system (CNS); (4) select the interaction of Wilder Penfield and Pío del Río-Hortega for a more in-depth historical vignette portraying a critical period during which glial cell types were being identified, described, and separated; and (5) briefly summarize further developments that presaged the modern era of neuroglioscience. In an endeavor of this kind, one must be sure to acknowledge those authors who have previously made strong attempts to synthesize information regarding the history of the concept of neuroglia. In particular, the efforts and publications of Helmut Kettenmann, Bruce Ransom, George Somjen, Alexei Verkhratsky, Arthur Butt, and Vladimir Parpura should be commended highly [1–7]. In contradistinction to the historical aspect of this chapter, see Chapter 2: Astrocytes in the Mammalian Brain will describe a more modern understanding of astrocytes in the mammalian brain.

Neuron Doctrine

Neuron theory or neuron doctrine asserts that nerve tissue is composed of individual cells which are anatomical and functional units called neurons. While generally attributed to Wilhelm Waldeyer who coined the term “neuron” in 1891 [8] and the neurohistological work of Santiago Ramón y Cajal [9], there were many scientific antecedents enabling the development of the neuron doctrine [10–13]. Microscopic imaging of the nerve cell in 1836 by Gabriel Valentin, visualization of the axon in 1837 by Robert Remak, development of “cell theory” by Schleiden and Schwann (1838–39), and discovery of the “Purkinje” cell by Jan Purkinje in 1839 were all seminal. The early proponents of the neuron doctrine, Wilhelm His, Fridtjof Nansen, and Auguste Forel, based partly on direct observations of Golgi-stained nerve cells and partly on credible generalizations, independently concluded that neurons are likely to be separate units [14–16]. In this section, we will explore the scientific antecedents to the neuron doctrine and the fascinating investigators involved.

Purkinje and Valentin’s Kugeln

Jan Evangelista Purkinje (1787–1869) (Fig. 1.1) served as the Chair of Physiology in Breslau (the modern-day Polish city, Wrocław) and made many valuable contributions to cell biology and neurobiology. Gabriel Valentin (1810–83) was one of his students assigned to study the nervous system. In 1836, Valentin described the nerve cell with remarkable accuracy using water-prepared tissue. He noticed small Kugeln (globules) which were clearly nerve cells. He described that the globule had a sharp outline (cell membrane) and an interior substance called parenchymasse (parenchyma) filled with viscous fluid containing numerous granules. Inside this was the nucleus and within it a small corpuscle (nucleolus). The very first description of the nerve cell body was made. Valentin and his mentor Purkinje had generally implied the idea of a “cell” but it was Schwann who proposed the unified “cell theory” and extolled its significance.

Figure 1.1 Jan Evangelista Purkinje (1787–1869).

Scheiden, Schwann, and Cell Theory

The development of the proposition, that there exists one general principle for the formation of all organic productions, and that this principle is the formation of cells, as well as the conclusions which may be drawn from this proposition, may be comprised under the term cell-theory, using it in its more extended signification, whilst in a more limited sense, by theory of the cells we understand whatever may be inferred from this proposition with respect to the powers from which these phenomena result [17,18].

Matthias Jakob Schleiden (1804–81) (Fig. 1.2) was a lawyer who went back to school to study medicine and eventually became a botanist. In 1838, Schleiden published a paper on the origins of the plant cell; despite some flawed conclusions, this paper contained the essential idea that plants are composed of cells [19]. Schleiden’s friend, the zoologist Theodor Schwann (1810–82) (Fig. 1.3), heard one of his ideas over dinner one October evening in 1838 [20]. Together, they went to the laboratory and examined sections of spinal cord that Schwann studied. Schleiden recognized the nuclei and their similarity to those of plant cells. That night, the first notion of a unified cellular theory was born. A year later, in 1839, Schwann published the cell theory for all living tissues (plants and animals) [17]. Interestingly, no mention of Schleiden was made! (Incidentally, it was Schleiden who influenced the young Carl Zeiss to form his subsequently very important optical firm, the fruits of which were much improved microscopes to the present day.)

Figure 1.2 Matthias Jakob Schleiden (1804–81).

Figure 1.3 Theodor Schwann (1810–82).

Remak’s Remarkable Observation

In his 1838 thesis, Robert Remak (1815–65) (Fig. 1.4) described peripheral nerves as a “primitive band” (axon) within a thin walled “primitive tube” (myelin sheath). These bands were later referred to as the “band of Remak” and synonymous with axon or axis cylinder. He also described sympathetic nerves which lacked the tubular covering and called them primitive fibers. They were later referred to as the “fiber of Remak.” A third contribution was relationship between the nerve and the nerve fiber: he stated that “[t]he organic fibers arise from the very substance of the nucleated globules.” Remak never conclusively backed his statement with evidence. It was a “remarkable observation” and in many ways years ahead of his time. The water preparation of these specimens and the associated swelling or shrinkage cast doubt over the accuracy of these findings. However, Remak was vociferous in his opinions and publicly acknowledged that his findings were contrary to Gabriel Valentin’s findings. In the pinnacle of his career, Remak was the first to suggest in 1855 that

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Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Preface
• Acknowledgments
• Chapter 1. History of Astrocytes
• Chapter 2. Astrocytes in the Mammalian Brain
• Chapter 3. Gliotransmitters
• Chapter 4. Types of Epilepsy
• Chapter 5. Neuropathology of Human Epilepsy
• Chapter 6. Astrocyte Calcium Signaling
• Chapter 7. Potassium Channels
• Chapter 8. Water Channels
• Chapter 9. Glutamate Metabolism
• Chapter 10. Adenosine Metabolism
• Chapter 11. Gap Junctions
• Chapter 12. Blood–Brain Barrier Disruption
• Chapter 13. Inflammation
• Chapter 14. Therapeutic Targets and Future Directions
• Index