Premium
Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis
Author(s) -
Brown David A.,
Sawchenko Paul E.
Publication year - 2007
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21307
Subject(s) - myelin oligodendrocyte glycoprotein , experimental autoimmune encephalomyelitis , pathogenesis , multiple sclerosis , pathology , microglia , biology , neurodegeneration , neuroscience , myelin , neuropathology , white matter , choroid plexus , inflammation , immunology , central nervous system , medicine , disease , radiology , magnetic resonance imaging
Murine models of experimental autoimmune encephalomyelitis (EAE) are important vehicles for studying the effects of genetic manipulation on disease processes related to multiple sclerosis (MS). Currently, a comprehensive assessment of EAE pathogenesis with respect to inflammatory and degenerating neuronal elements is lacking. By using Fluoro‐jade histochemistry to mark neurodegeneration and dual immunostaining to follow T‐cell, microglial, and vascular responses, the time course and distribution of pathological events in EAE was surveyed. C57BL/6J mice were killed at 7, 10, 14, 21 or 35 days after vaccination with the myelin oligodendrocyte glycoprotein peptide MOG 35–55 . Disease onset occurred at day 14 and peaked at day 21. Early T‐cell infiltration and microglial activation in periventricular and superficial white matter structures adjacent to meninges suggested initial recruitment of effector T cells via the cerebrospinal fluid and choroid plexus. This was associated with microglial activation at distal sites along the same white matter tracts, with subsequent vascular recruitment of T cells associated with further injury. Systematic examination of the entire CNS supported this two‐step model of EAE pathogenesis, with inflammation and neurodegeneration commencing at similar times and affecting multiple levels of predominantly sensory central pathways, including their terminal fields. This included aspects of the visual, auditory/vestibular, somatosensory (lemniscal), and proprioceptive (spinocerebellar) systems. The early targeting of visual and periventricular structures followed by more widespread CNS involvement is consistent with common presenting signs in human MS patients and suggestive of a similar basis in neuropathology. J. Comp. Neurol. 502:236–260, 2007. © 2007 Wiley‐Liss, Inc.