Research into inflammatory mechanisms that may cause damage to the Alzheimer's disease (AD) brain has now been ongoing for nearly two decades. Some two dozen clinical studies have strongly suggested that conventional anti-inflammatory drugs may be useful to delay the onset or slow the progression of the disorder. Moreover, virtually all the major systems of the innate immune response appear to be present, and most are upregulated, in pathologically-vulnerable regions of the AD brain. These new findings are described in this volume - first in overview form, followed by chapters on topics of special interest. In many ways, to understand AD brain inflammation, one need only review a text on peripheral inflammation biology, leaving out the chapters on humoral medi ators and substituting microglia for macrophages. In several other key respects, however, AD brain inflammation is unique, due primarily to idiosyncratic interac tions of inflammatory mediators and mechanisms with classical AD pathology: amyloid ~ peptide(A~) deposits and neurofibrillary tangles (NFTs). For this reason, some key concepts about the inflammation that occurs in AD may warrant discus sion in preparation for the more detailed chapters that follow.

In this thoroughly updated and revised edition of his much praised book, Paul L. Wood and a panel of leading researchers capture these new developments in a masterful synthesis of what is known today about the inflammatory mediators and cells involved in neurodegenerative diseases. This second edition contains extensive updates on the mediators produced by microglia and their role in neuroinflammatory-induced neuronal lysis. There is also increased coverage of the animal models used in the study of neuroinflammatory mechanisms, of the new imaging methods that allow the noninvasive evaluation of microglial activation in human neurodegernerative disorders, and of the role of neuroinflammation in amyloid-dependent neuronal lysis.

"Mechanisms of Neuroinflammation" book explains how the neuronal cells become swollen at the moment of the blood-brain barrier disruption and how they lose their immunological isolation. A cascade of cytokines and immune cells from the bloodstream enters the nervous system, inflaming neurons and activating the glia. This produces a neuroinflammatory process that can generate different neurodegenerative diseases. Better understanding of mechanisms that are activated at the time when the damage to the brain occurs could lead to the development of suitable therapies that revert the neuronal inflammation and thus prevent further damage to the nervous system.

Mechanisms of brain-immune interactions became a cutting-edge topic in systemic neurosciences over the past years. Acute lesions of the brain parenchyma, particularly, induce a profound and highly complex neuroinflammatory reaction with similar mechanistic properties between differing disease paradigms like ischemic stroke, intracerebral hemorrhage (ICH) and traumatic brain injury (TBI). Resident microglial cells sense tissue damage and initiate inflammation, activation of the endothelial brain-immune interface promotes recruitment of systemic immune cells to the brain and systemic humoral immune mediators (e.g. complements and cytokines) enter the brain through the damaged blood-brain barrier. These cellular and humoral constituents of the neuroinflammatory reaction to brain injury contribute substantially to secondary brain damage and neurodegeneration. Diverse inflammatory cascades such as pro-inflammatory cytokine secretion of invading leukocytes and direct cell-cell-contact cytotoxicity between lymphocytes and neurons have been demonstrated to mediate the inflammatory ‘collateral damage’ in models of acute brain injury. Besides mediating neuronal cell loss and degeneration, secondary inflammatory mechanisms also contribute to functional modulation of neurons and the impact of post-lesional neuroinflammation can even be detected on the behavioral level. The contribution of several specific immune cell subpopulations to the complex orchestration of secondary neuroinflammation has been revealed just recently. However, the differential vulnerability of specific neuronal cell types and the molecular mechanisms of inflammatory neurodegeneration are still elusive. Furthermore, we are only on the verge of characterizing the control of long-term recovery and neuronal plasticity after brain damage by inflammatory pathways. Yet, a more detailed but also comprehensive understanding of the multifaceted interaction of these two supersystems is of direct translational relevance. Immunotherapeutic strategies currently shift to the center of translational research in acute CNS lesion since all clinical trials investigating direct neuroprotective therapies failed. To advance our knowledge on brain-immune communications after brain damage an interdisciplinary approach covered by cellular neuroscience as well as neuroimmunology, brain imaging and behavioral sciences is crucial to thoroughly depict the intricate mechanisms.