Neuroinflammation In Stroke

The successful treatment of acute stroke remains one of the major challenges in clinical medicine. Over the last decades, the understanding of stroke pathophysiology has greatly improved, while the therapeutic options in stroke therapy remain very limited. Today, hyperacute mechanisms of damage, such as excitotoxicity, can be discriminated from delayed ones, such as inflammation and apoptosis. Targeting of inflammation has already been successfully applied in various stroke models, but translation into a clinically efficacious strategy has not been achieved so far. In this book, leading experts in basic cerebrovascular research as well as stroke treatment review the current evidence for and against an important role for inflammation in stroke, and explore the potential of treating or modulating inflammation in stroke therapy.

Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. One possible explanation is that research and pharmacological management have focused on very early events in brain ischemia. New research has shown that brain ischemia and trauma elicit strong inflammatory reactions driven by both external and brain cells. The recognition of inflammation as a fundamental response to brain ischemia provides novel opportunities for new anti-inflammatory therapies. For the first time, an international body of researchers presents the latest findings about the cellular and humoral aspects of immune and inflammatory reactions in the brain. The work may have an impact on the treatment of neuroinjuries and ancillary brain diseases, and increase the understanding of the roles infections and immune reactions play in the brain milieu.

Ischemic stroke is a devastating clinical event. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of post ischemic-induced brain injury. Cerebral ischemia is accompanied by a marked inflammatory reaction that is initiated by ischemia-induced expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids, extracellular proteases, reactive oxygen species and nitric oxide, leading to the accumulation of inflammatory cells, such as leukocytes and microglia. The inflammatory reaction, which has a rapid onset and continues after the stroke, is thought to acutely contribute to the evolution of tissue injury. Many compounds have been identified in cerebral ischemia, which are known to promote and sustain inflammatory responses. Better understanding of the role of the post ischemic-induced inflammatory response and its potential for modulation might have profound implications for patient treatment. Pre-clinical studies suggest that interventions that are aimed at attenuating such inflammation reduce the progression of brain damage that occurs during the late stages of cerebral ischemia. In particular, strategies that block the activity of inflammation-related enzymes reduce ischemic damage with an extended therapeutic window. In this review, a summary of the available literature on the inflammatory responses after cerebral ischemia and ischemic stroke is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies. Although at the moment, clinical trials using anti-inflammatory strategies did not show benefit in patients with ischemic stroke, there is a strong rationale for continuing to explore the efficacy of anti-inflammatory therapies in the treatment of the late stages of cerebral ischemia. It is plausible that in the near future, additional strategies using neuroprotective drug cocktails that target inflammation could offer exciting new promise in the therapeutic approach to ischemic stroke.

Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. One possible explanation is that research and pharmacological management have focused on very early events in brain ischemia. New research has shown that brain ischemia and trauma elicit strong inflammatory reactions driven by both external and brain cells. The recognition of inflammation as a fundamental response to brain ischemia provides novel opportunities for new anti-inflammatory therapies. For the first time, an international body of researchers presents the latest findings about the cellular and humoral aspects of immune and inflammatory reactions in the brain. The work may have an impact on the treatment of neuroinjuries and ancillary brain diseases, and increase the understanding of the roles infections and immune reactions play in the brain milieu.

Recent research has revealed the importance of immunological mechanisms and inflammation in delaying damage and/or promoting repair after an acute injury to the central nervous system. This book provides a comprehensive and up-to-date overview of the role of immunological mechanisms and therapies for treating acute neurological injuries such as cerebral ischemia, hemorrhage, and brain and spinal cord trauma. In several sections, the contributing authors provide a review of immunological mechanisms involved in neurological injury and of various translational and clinical research aimed at harnessing those mechanisms for better patient outcomes.​

"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.

This book deals with the subject of neuroinflammation and attempts to take the reader on a journey from the bench to the bedside. The microglia and their response to brain injury as well as the importance of the chemokine family are discussed. The relevance of neuroinflammation in experimental models of BSE, scrapie and vCJD as well as Alzheimer's disease, stroke and multiple sclerosis is investigated before proceeding to clinical aspects of neuroinflammation and its involvement in human disease pathophysiology. The book provides an excellent introduction to the field of neuroinflammation and its involvement in human neurodegenerative disease.