Substantial early, but nonprogressive neuronal loss in multiple sclerosis (ms) spinal cord

Research in multiple sclerosis (MS) has recently been focusing on the extent of neuroaxonal damage and its contribution to disease outcome. In the present study, we examined spinal cord tissue from 30 clinically well‐characterized MS patients. MS, amyotrophic lateral sclerosis (ALS), and control spinal cord tissue were subjected to morphometric analysis and immunohistochemistry for markers of cell damage and regeneration. Data were related to disease duration and age at death. Here, we present evidence for substantial, nonprogressive neuronal loss on the cervical and lumbar levels early in the disease course of MS. Chromatolytic neurons and immunoreactivity for c‐Jun and GAP43 were observed in the ventral gray matter in and adjacent to actively demyelinating lesions, pointing toward neuronal damage and regeneration as an early response to lesion formation. Ann Neurol 2009;66:698–704

[1]  M. Esiri,et al.  Spinal Cord Neuronal Pathology in Multiple Sclerosis , 2009, Brain pathology.

[2]  M. Filippi,et al.  In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. , 2007, Brain : a journal of neurology.

[3]  P. Matthews,et al.  Neocortical neuronal, synaptic, and glial loss in multiple sclerosis , 2006, Neurology.

[4]  James Lowe,et al.  Spinal Cord Gray Matter Demyelination in Multiple Sclerosis—A Novel Pattern of Residual Plaque Morphology , 2006, Brain pathology.

[5]  K. Yaddanapudi,et al.  Metallothioneins and Zinc Dysregulation Contribute to Neurodevelopmental Damage in a Model of Perinatal Viral Infection , 2006, Brain pathology.

[6]  Roberto Mutani,et al.  Grey Matter Pathology in Multiple Sclerosis , 2005, Journal of neuropathology and experimental neurology.

[7]  D. Pleasure,et al.  Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice. , 2005, Brain : a journal of neurology.

[8]  M. Esiri,et al.  Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions. , 2004, Brain : a journal of neurology.

[9]  P. Matthews,et al.  Thalamic neurodegeneration in multiple sclerosis , 2002, Annals of neurology.

[10]  Wolfgang Brück,et al.  Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. , 2002, Brain : a journal of neurology.

[11]  W. Brück,et al.  BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? , 2002, Brain : a journal of neurology.

[12]  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.

[13]  L. Turski,et al.  Autoimmune encephalomyelitis ameliorated by AMPA antagonists , 2000, Nature Medicine.

[14]  P M Matthews,et al.  Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. , 1998, Brain : a journal of neurology.

[15]  J. Noth,et al.  Distribution of B-50(GAP-43) mRNA and protein in the normal adult human spinal cord , 1998, Acta Neuropathologica.

[16]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[17]  A. Krassioukov,et al.  Changes in immunoreactivity for growth associated protein-43 suggest reorganization of synapses on spinal sympathetic neurons after cord transection , 1997, Neuroscience.

[18]  T. Herdegen,et al.  The c-Jun transcription factor – bipotential mediator of neuronal death, survival and regeneration , 1997, Trends in Neurosciences.

[19]  Aryeh Routtenberg,et al.  GAP-43: an intrinsic determinant of neuronal development and plasticity , 1997, Trends in Neurosciences.

[20]  X. Montalban,et al.  Jun expression is found in neurons located in the vicinity of subacute plaques in patients with multiple sclerosis , 1996, Neuroscience Letters.

[21]  A. Thompson,et al.  Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. , 1996, Brain : a journal of neurology.

[22]  Hans Lassmann,et al.  Monocyte/macrophage differentiation in early multiple sclerosis lesions , 1995, Annals of neurology.

[23]  D. Price,et al.  Ventral root avulsion: An experimental model of death of adult motor neurons , 1994, The Journal of comparative neurology.

[24]  E. Brambilla,et al.  F(ab) secondary antibodies: a general method for double immunolabeling with primary antisera from the same species. Efficiency control by chemiluminescence. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[25]  D. G. Ferguson,et al.  An indirect immunofluorescence procedure for staining the same cryosection with two mouse monoclonal primary antibodies. , 1993, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.