Profiling and Identification of Cerebrospinal Fluid Proteins in a Rat EAE Model of Multiple Sclerosis

The experimental autoimmune encephalomyelitis (EAE) model
resembles
certain aspects of multiple sclerosis (MScl), with common features
such as motor dysfunction, axonal degradation, and infiltration of
T-cells. We studied the cerebrospinal fluid (CSF) proteome in the
EAE rat model to identify proteomic changes relevant for MScl disease
pathology. EAE was induced in male Lewis rats by injection of myelin
basic protein (MBP) together with complete Freund’s adjuvant
(CFA). An inflammatory control group was injected with CFA alone,
and a nontreated group served as healthy control. CSF was collected
at day 10 and 14 after immunization and analyzed by bottom-up proteomics
on Orbitrap LC–MS and QTOF LC–MS platforms in two independent
laboratories. By combining results, 44 proteins were discovered to
be significantly increased in EAE animals compared to both control
groups, 25 of which have not been mentioned in relation to the EAE
model before. Lysozyme C1, fetuin B, T-kininogen, serum paraoxonase/arylesterase
1, glutathione peroxidase 3, complement C3, and afamin are among the
proteins significantly elevated in this rat EAE model. Two proteins,
afamin and complement C3, were validated in an independent sample
set using quantitative selected reaction monitoring mass spectrometry.
The molecular weights of the identified differentially abundant proteins
indicated an increased transport across the blood–brain barrier
(BBB) at the peak of the disease, caused by an increase in BBB permeability.