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Neuronal survival and functions require bidirectional communication between neurons and glia that involves a large variety of growth factors. Neurotrophic factors are operationally defined as proteins that regulate neuron survival and differentiation. They can be synthesized by nonneuronal target cells, neurons, and glial cells. This chapter focuses on neurotrophic factors secreted from macroglial cells, that is, astrocytes, oligodendrocytes, and Schwann cells, and their effects on neuronal differentiation and survival in the intact and lesioned brain and peripheral nervous system.

Oligodendrocytes and Schwann cells are responsible for synthesis and maintenance of myelin in the central nervous system (CNS) and peripheral nervous system (PNS), respectively, and therefore are critical for function in health and disease. Damage to myelin is a common feature in many neurological disorders, leading to delayed or blocked axonal conduction, secondary damage to axons, and possible permanent neurological dysfunction. There is growing recognition that oligodendrocytes and Schwann cells are uniquely vulnerable to a number of injury mechanisms. This chapter reviews molecular mechanisms leading to death in oligodendrocyte and Schwann cell lineages, including pathways triggered by oxidative stress, excitotoxicity, inflammatory mediators, and trophic factor deprivation. It also considers cell-cell interactions involved in white matter damage and the implications for clinical outcomes as well as potential avenues of treatment.

This chapter begins by looking at the principal mechanisms of ischemic damage and identifies what is known about the specific contribution of glial cells. It then changes the perspective from affected tissue to single cells and reassesses the specific contribution of the glial cell types (astroglia, microglia, oligodendrocytes) in this process. Glial cells are major contributors to damage, as well as to endogenous protection and repair after stroke. The fact that the same cell types partake in damaging as well as protective signaling precludes simple therapeutic approaches aimed at blocking or inducing the activities of glial cells. Nevertheless, the recent appreciation of the high susceptibility of oligodendrocytes to AMPA-mediated cell death and the successful pilot trial on the use of EPO in stroke in humans are examples of the outstanding clinical relevance of glial mechanisms in stroke.

This chapter provides a historical perspective that highlights the early period of glial research. Topics covered include Virchow's invention of the term neuroglia in 1856, Heinrich Müller' picture of a glial cell, stellate cells in white and gray matter, and Camillo Golgi's description of cells with characteristic features of astrocytes and oligodendrocytes.

This chapter discusses astrocytes and ependymal glia. Macroglial cells, which comprise oligodendrocytes, astrocytes, and ependymoglial cells, may be classified according to the shapes and contacts of their cell processes. In contrast to oligodendrocytes, astroglial and ependymoglial cells are characterized by endfeet that contact a basal lamina around blood vessels and/or the pia mater or the vitreous body of the eye. Ependymoglial cells display a bipolar shape and additionally contact the ventricular surface (or the subretinal space). Astrocytes may be radially orientated but never contact the ventricular system.

This chapter on estrogenic regulation of glia and neuroinflammation reviews the role of glial cells in the modulation of synaptic function under physiological conditions and in the regulation of the neuroinflammatory response under pathological conditions. The anti-inflammatory actions of estradiol on astrocytes, oligodendrocytes, and microglia and the implication of these actions for the neuroprotective and tissue repair effects of the hormone are also discussed. Finally, the therapeutic potential of synthetic and natural estrogenic compounds for the control of neuroinflammation is examined. Because reducing neuroinflammation prevents the progressive loss of neural structure and function that leads to functional and mental impairments, regulation of glial cell activation via estradiol is a promising therapeutic approach.

Dental students and practitioners need a working knowledge of the central nervous system (CNS) for several reasons. • A general knowledge of the structure and function of the nervous system is required to understand the major roles it plays in controlling body functions. • The cranial nerves innervating the head and neck, including the oral cavity, underpin all functions in these areas; knowledge of these nerves, including their connections to the CNS is vital to understanding the anatomy and physiology of this region. • Clinically, dental students and practitioners will frequently encounter patients suffering from one or other of the many diseases affecting the central and peripheral nervous system. Satisfactory dental management of such patients requires some understanding of their illness which in turn requires knowledge of the general structure of the nervous system. The anatomy of the nervous system was described long before we understood much of its function. Like all other parts of the body, everything is named; some of the names seem to defy the logic of anatomical nomenclature used to describe structures elsewhere in the body introduced in Chapter 1. Some of the structures visible to the naked eye were named by their fanciful resemblance to everyday objects such as olives; their names, therefore, bear no resemblance to their function. However, the nerve tracts that connect different areas to form functional pathways are described using a consistent system of naming. Only the most important structures that can be observed in dissected brains or form important landmarks in functional pathways are included in these chapters on the nervous system. It is important to appreciate that much of the detailed structure of the brain can only be observed microscopically. Special microscopical methods are required to show its structure and even then, a practised eye is required to interpret them. Nevertheless, it does help to know the outline of how the connections and functions of the nervous system have been investigated to understand how we have arrived at our present level of knowledge. Initially, careful clinical observations of signs and symptoms prior to death were correlated with post-mortem changes in the brain.

The vast majority of nerve cells generate a series of brief voltage pulses in response to vigorous input. These pulses, also referred to as action potentials or spikes, originate at or close to the cell body, and propagate down the axon at constant velocity and amplitude. Fig. 6.1 shows the shape of the action potential from a number of different neuronal and nonneuronal preparations. Action potentials come in a variety of shapes; common to all is the all-or-none depolarization of the membrane beyond 0. That is, if the voltage fails to exceed a particular threshold value, no spike is initiated and the potential returns to its baseline level. If the voltage threshold is exceeded, the membrane executes a stereotyped voltage trajectory that reflects membrane properties and not the input. As evident in Fig. 6.1, the shape of the action potential can vary enormously from cell type to cell type. When inserting an electrode into a brain, the small all-or-none electrical events one observes extracellularly are usually due to spikes that are initiated close to the cell body and that propagate along the axons. When measuring the electrical potential across the membrane, these spikes peak between +10 and +30 mV and are over (depending on the temperature) within 1 or 2 msec. Other all-or-none events, such as the complex spikes in cerebellar Purkinje cells or bursting pyramidal cells in cortex, show a more complex wave form with one or more fast spikes superimposed onto an underlying, much slower depolarization. Finally, under certain conditions, the dendritic membrane can also generate all-or-none events that are much slower than somatic spikes, usually on the order to 50-100 msec or longer. We will treat these events and their possible significance in Chap. 19. Only a small fraction of all neurons is unable—under physiological conditions—to generate action potentials, making exclusive use of graded signals. Examples of such nonspiking cells, usually spatially compact, can be found in the distal retina (e.g., bipolar, horizontal, and certain types of amacrine cells) and many neurons in the sensory-motor pathway of invertebrates (Roberts and Bush, 1981).