Early detection of the chemical changes occurring during the induction and prevention of autoimmune-mediated demyelination detected by FT-IR imaging.
Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Despite progress in understanding immunogenetic aspects of this disease, the mechanisms involved in lesion formation are unknown. To gain new insights into the neuropathology of MS, we used an innovative integration of Fourier transform infrared (FT-IR) microspectroscopy, bioinformatics, and a synchrotron light source to analyze macromolecular changes in the CNS during the course and prevention of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We report that subtle chemical and structural changes not observed by conventional histology were detected before the onset of clinical signs of EAE. Moreover, trained artificial neural networks (ANNs) could discriminate, with excellent sensitivity and specificity, pathology from surrounding tissues and the early stage of the disease progression. Notably, we show that this novel measurement platform can detect characteristic differences in biochemical composition of lesion pathology in animals partially protected against EAE by vaccination with Nogo-A, an inhibitor of neural outgrowth, demonstrating the potential for automated screening and evaluation of new therapeutic agents.
Multiple Sclerosis Research Group, Monash Immunology and Stem Cell Laboratories, Monash University, Wellington Road, Victoria 3800, Australia.
Philip
P
Heraud
Sally
S
Caine
Naomi
N
Campanale
Tara
T
Karnezis
Don
D
McNaughton
Bayden R
BR
Wood
Mark J
MJ
Tobin
Claude C A
CC
Bernard
D000818:Animals; D001331:Automation; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis; D009185:Myelin Proteins / Q000276:immunology / Q000627:therapeutic use; D016571:Neural Networks, Computer; D000070798:Nogo Proteins; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013997:Time Factors; D014611:Vaccination
D009185:Myelin Proteins; D000070798:Nogo Proteins; D010455:Peptides; C000603201:Rtn4 protein, mouse