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J Neurol Sci. 2012 Jan 15;312(1-2):146-57. doi: 10.1016/j.jns.2011.07.050. Epub 2011 Oct 13.

Preimplantation factor (PIF*) reverses neuroinflammation while promoting neural repair in EAE model.

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1
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital Ein Kerem, Hebrew University, Jerusalem, Israel.

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<0.05). Episodic sPIF reversed chronic paralysis (P<0.0001) completely in >50%, by day 82. Prevention model: 12days 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.

PMID:
21996270
DOI:
10.1016/j.jns.2011.07.050
[Indexed for MEDLINE]
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