Neural Dynamics of Neurological Disease

Christopher A. Shaw

• Publisher: Wiley-Blackwell
• Year: 2017
• Print ISBN: 9781118634578
• eBook ISBN: 9781118634738
• Edition: 1
• Topic: Biowissenschaften
• Subtopic: Neurowissenschaft

The emerging understanding of age-related neurological disorders suggests that notions of a single causal gene/toxin being responsible is likely incorrect. Neurological disorders probably arise due to a unique intersection of multiple genetic and toxic factors, combined with additional contributions of age, stage of development, immune system actions, and more. This perspective leads to the view that rather than reflecting only one pathway to end-state disease, each is a spectrum disorder, and every individual case is therefore unique.

Neural Dynamics of Neurological Disease argues for a fundamental rethinking of what we think we know about neurological disorders, how they arise and progress, and, crucially, what might be done to "cure" them. It first introduces the concept of neural dynamics of neurological disease, then examines various diseases and gives examples of the interplay of elements such as neural systems, cell types, and biochemical pathways that can contribute to disease. The concluding chapters point the way to how the emerging notion of neurological disease as a dynamic process may lead to more successful treatment options.

Providing a cross-disciplinary approach to understanding the origin and progression of neurological disease, Neural Dynamics of Neurological Disease is a timely and valuable resource for neuroscientists, researchers, and clinicians.

Part I

The Dynamics of Neurological Disease

Chapter 1
The Dynamics of Neurological Disease: Current Views and Key Issues

It was six men of Indostan

To learning much inclined,

Who went to see the Elephant

(Though all of them were blind),

That each by observation

Might satisfy his mind.

The First approach'd the Elephant,

And happening to fall

Against his broad and sturdy side,

At once began to bawl:

“God bless me! but the Elephant

Is very like a wall!”

The Second, feeling of the tusk,

Cried, –“Ho! what have we here

So very round and smooth and sharp?

To me 'tis mighty clear

This wonder of an Elephant

Is very like a spear!” [etc.¹]

John Godfrey Saxe

From the Preface

1. 1. The human CNS is complex. It contains something on the order of 86 billion neurons, organized into multiple subsystems, surrounded by 85 billion supporting glial cells. Neurons are totally dependent on these support cells for their normal functions. Each neuron connects to multiple other neurons for an estimated 94 trillion synaptic connections. There should be nothing particularly controversial about anything in this paragraph for anyone in neuroscience/neurological disease research.

1. 5. For all of these reasons, neurological diseases that are age-related (e.g., Parkinson's disease, ALS, Alzheimer's disease, and others) are going to be complex as well. The same applies to neuronal disorders at the other end of the age spectrum (e.g., autism spectrum disorder (ASD)).

1.1 Introduction

Certainly the first thing to consider when contemplating the human nervous system in health or disease is its overall complexity. In regard to the latter, the subject of this book, the sheer number of individual elements alone means that there are going to be multiple ways for any part of the system, any subsystem, or even individual cells such as the types of neurons and glia, to malfunction. Add to this the vast number of interconnections between neurons, circuits, and systems, and the potential for multiple forms of dysfunction grows greater still.

However, before considering how the human central nervous system (CNS) evolves into a disease state, it is important to appreciate just how utterly complex the system actually is.

1.2 The Complexity of Human Neurological Diseases

Few neuroscientists would disagree with the view that the human nervous system in general is quite complex. Indeed, some scholars and lay persons from various disciplines have opined that it is the most complex thing in the universe, or at least the most complex that humans know about. This last clause is essential given the robust hubris of Homo sapiens.

Regardless of just how complex the human nervous system is in the context of the rest of the universe, the questions which arise are these: First, how does such a complex system come into existence? Second, for the purposes of this book, how does it break down? It may be worth noting here that the nervous systems of most vertebrates are also relatively complex, particularly those of mammals. Largely for this reason, attempts to provide comprehensive and predictive animal models of neurological diseases are almost certain to run into many of the same problems as those associated with trying to understand the human CNS in the various states in which it may be, or become in the future.

The answer to the first question is the subject of developmental neurobiology, which examines the genetic and environmental factors underlying the formation of nervous system structure and function. In the latter regard, much has been learned about developmental features of the nervous system, the early and late forms of modifications, often termed “neuroplasticity,” and the implications of the latter in particular for the remarkable capacity that any nervous system has to modify itself and thus alter behavioral responses to changing external circumstances (for a general review, see Shaw and McEachern, 2001).

The broad subject matter that comes under the rubric of neuroplasticity has been the focus of innumerable scientific research papers, reviews, and books. I was a co-editor of one of the latter, Toward a Theory of Neuroplasticity (Shaw and McEachern, 2001), which attempted to come to grips with the extensive subject matter at the time, a literature that will only have grown in the intervening years. The general topic of neuroplasticity will be considered here only in the context of the second question which is the focus of the chapters that follow.

Restating that question, can an admittedly complex structure/system be destroyed in a simple, perhaps unitary way, or must the innate complexity of the system in the first place make the dissolution of the system complex as well?

The answer is that both can occur, but with very different characteristics, depending on a spectrum of types of injury. For example, acute injury to the brain in the form of gunshot wounds or other major head trauma can certainly destroy the system rapidly. The myriad cellular chemicals and processes that are almost immediately released by macroscopic damage lead to the microscopic destruction of cells in a time frame of seconds to minutes. In the middle of the spectrum are traumatic injuries to the CNS that cause some level of destruction of neurons and glial cells, which may not be instantly fatal to the individual. In such cases, such as in cortical stroke or spinal cord damage, the initial trauma is often followed by secondary damage to surrounding neural cells and it is the latter that tends to exacerbate the initial injury. Indeed, such secondary damage may eventually be of larger scale and impact than the initial insult (Oyinbo, 2011).

At the other end of the spectrum are the so-called “progressive,” age-related neurodegenerative diseases, which are neither acute in their initial stages, nor, as far as is known, of rapid onset. Rather, these “classical” neurological diseases (i.e., Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease; Figure 1.1) appear in most cases to be more insidious in onset and progression. In general, there are few reasons to believe that these diseases arise in a short time period. There may, however, be exceptions.

Figure 1.1 Discoverers of the progressive, age-related neurological diseases and their famous victims (top to bottom): James Parkinson (Parkinson's disease was first described in his “Essay on the Shaking Palsy”; note that a verified picture of James Parkinson does not seem to be extant) and Michael J. Fox; Jean-Martin Charcot and Henry Louis (“Lou”) Gehrig; Alois Alzheimer and Ronald Reagan.

For example, forms of what look to be ALS-like motor neuron disorders have arisen relatively rapidly in some Gulf War Syndrome victims (Haley, 2003). Additionally, some ALS-like disorders in young women have been linked, at least temporally, to human papilloma virus (HPV) vaccine adverse reactions (Huang et al., 2009). In addition, there is a rapid-onset form of parkinsonism, now the basis of one of the ...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• Dedication
• Preface
• Acknowledgments
• Part I: The Dynamics of Neurological Disease
• Part II: Age and Time Lines of Neurological Disease
• Part III: Interactions and Synergies in Neurological Disease
• Part IV: Transition and Politics in Neurological Disease
• Glossary
• References 1: References
• Index
• End User License Agreement