Neuronal damage in brain inflammation.

In contrast to traditional textbook paradigms, recent studies indicate neuronal damage in classic neuroinflammatory diseases of the brain, such as multiple sclerosis or meningitis. In these cases, immune cells invade the central nervous system compartments, accompanied by a massive breakdown of the blood-brain barrier and typical changes of the cerebrospinal fluid. On the other hand, inflammation within the central nervous system is a common phenomenon even in classic noninflammatory brain diseases that are characterized by degeneration or trauma of neuronal structures, such as Alzheimer disease, Parkinson disease, or stroke. In these cases, inflammation is a frequent occurrence but displays different, more subtle, patterns compared with, for example, multiple sclerosis. Concepts for directly protecting neurons and axons in neuroinflammatory diseases may improve the outcome of the patients. In parallel, epidemiological and animal experimental evidences, as well as first clinical trials indicate the benefit of immunomodulatory therapies for classic noninflammatory brain diseases. We review the evidence for inflammatory neuronal damage and its clinical impact in the context of these diseases.

[1]  E. Frohman,et al.  Multiple sclerosis--the plaque and its pathogenesis. , 2006, The New England journal of medicine.

[2]  R. Nitsch,et al.  The Endocannabinoid Anandamide Protects Neurons during CNS Inflammation by Induction of MKP-1 in Microglial Cells , 2006, Neuron.

[3]  L. Steinman,et al.  Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. , 2005, Trends in immunology.

[4]  N. Rothwell,et al.  A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[5]  N. Rothwell,et al.  Interleukin-1 and neuronal injury , 2005, Nature Reviews Immunology.

[6]  R. Gold,et al.  Mechanisms of axonal degeneration in EAE—lessons from CNTF and MHC I knockout mice , 2005, Journal of the Neurological Sciences.

[7]  I. Bechmann,et al.  Neuronal Damage in Autoimmune Neuroinflammation Mediated by the Death Ligand TRAIL , 2005, Neuron.

[8]  P. S. St George-Hyslop,et al.  Immunotherapy for Alzheimer's disease , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Gendelman,et al.  Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  F. Zipp,et al.  Direct Impact of T Cells on Neurons Revealed by Two-Photon Microscopy in Living Brain Tissue , 2004, The Journal of Neuroscience.

[11]  Harald Neumann,et al.  Neuronal injury mediated via stimulation of microglial toll‐like receptor‐9 (TLR9) , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  F. Zipp,et al.  Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation , 2003, The Journal of experimental medicine.

[13]  U. Dirnagl,et al.  Stroke-induced Immunodeficiency Promotes Spontaneous Bacterial Infections and Is Mediated by Sympathetic Activation Reversal by Poststroke T Helper Cell Type 1–like Immunostimulation , 2003, The Journal of experimental medicine.

[14]  A. Dale,et al.  Focal thinning of the cerebral cortex in multiple sclerosis. , 2003, Brain : a journal of neurology.

[15]  R. McCarron,et al.  Adoptive Transfer of Myelin Basic Protein–Tolerized Splenocytes to Naive Animals Reduces Infarct Size: A Role for Lymphocytes in Ischemic Brain Injury? , 2003, Stroke.

[16]  B. Trapp,et al.  Subpial Demyelination in the Cerebral Cortex of Multiple Sclerosis Patients , 2003, Journal of neuropathology and experimental neurology.

[17]  C. Holmes,et al.  Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report , 2003, Nature Medicine.

[18]  S. Waxman.  Nitric oxide and the axonal death cascade , 2003, Annals of neurology.

[19]  H. Lassmann,et al.  CNTF is a major protective factor in demyelinating CNS disease: A neurotrophic cytokine as modulator in neuroinflammation , 2002, Nature Medicine.

[20]  H. Neumann,et al.  Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases , 2002, Trends in Neurosciences.

[21]  W. Brück,et al.  Neuronal injury in bacterial meningitis: mechanisms and implications for therapy , 2002, Trends in Neurosciences.

[22]  B. Trapp,et al.  Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions , 2001, Annals of neurology.

[23]  R. Rudick,et al.  Neurological disability correlates with spinal cord axonal loss and reduced N‐acetyl aspartate in chronic multiple sclerosis patients , 2000, Annals of neurology.

[24]  I. Bechmann,et al.  Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) , 2000, The Lancet.

[25]  C. Plata-salamán,et al.  Inflammation and Alzheimer’s disease , 2000, Neurobiology of Aging.

[26]  M. Moskowitz,et al.  Pathobiology of ischaemic stroke: an integrated view , 1999, Trends in Neurosciences.

[27]  I. Herr,et al.  CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons , 1999, The Journal of Neuroscience.

[28]  K. Nave,et al.  Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. , 1998, Science.

[29]  J. Cleveland,et al.  Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. , 2002, The Journal of clinical investigation.

[30]  P M Matthews,et al.  Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. , 2001, Archives of neurology.