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Preimplantation Factor (PIF*) reverses neuroinflammation while promoting neural repair in EAE model
- Source :
- Journal of the Neurological Sciences. 312:146-157
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Introduction Embryo-derived PIF modulates systemic maternal immunity without suppression. Synthetic analog (sPIF) prevents juvenile diabetes, preserves islet function, reducing oxidative stress/protein misfolding. We investigate sPIF effectiveness in controlling neuroinflammation/MS. Methods Examine sPIF-induced protection against harsh, clinical-relevant murine EAE-PLP acute and chronic models. Evaluate clinical indices: circulating cytokines, spinal cord histology, genome, canonical global proteome, cultured PLP-activated splenocytes cytokines, and immunophenotype. Results Short-term, low-dose sPIF prevented paralysis development and lowered mortality (P 50%, by day 82. Prevention model: 12 days post-therapy, sPIF reduced circulating IL12 ten-fold and inflammatory cells access to spinal cord. Regression model: sPIF blocked PLP-induced IL17 and IL6 secretions. Long-term chronic model: sPIF reduced spinal cord pro-inflammatory cytokines/chemokines, (ALCAM, CF1, CCL8), apoptosis-promoters, inflammatory cells access (JAM3, OPA1), solute channels (ATPases), aberrant coagulation factors (Serpins), and pro-antigenic MOG. Canonical proteomic analysis demonstrated reduced oxidative phosphorylation, vesicle traffic, cytoskeleton remodeling involved in neuro-cytoskeleton breakdown (tubulins), associated with axon re-assembly by (MTAPs)/improved synaptic transmission. Conclusion sPIF – through coordinated central and systemic multi-targeted action – reverses neuroinflammation/MS and imparts significant neuroprotective effects up to total paralysis resolution. Clinical testing is warranted and planned.
- Subjects :
- Chemokine
Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
Mice, Inbred Strains
Biology
medicine.disease_cause
CCL8
Neuroprotection
Mice
Random Allocation
medicine
Animals
Axon
Neuroinflammation
ALCAM
Neurogenesis
Nerve Regeneration
Disease Models, Animal
medicine.anatomical_structure
Neurology
Immunology
biology.protein
Female
Neurology (clinical)
Inflammation Mediators
Peptides
Oxidative stress
Subjects
Details
- ISSN :
- 0022510X
- Volume :
- 312
- Database :
- OpenAIRE
- Journal :
- Journal of the Neurological Sciences
- Accession number :
- edsair.doi.dedup.....e50c38e6a7d5fa2d805cddb408856bba