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

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.

journal_name

J Neurol Sci

authors

Weiss L,Or R,Jones RC,Amunugama R,JeBailey L,Ramu S,Bernstein SA,Yekhtin Z,Almogi-Hazan O,Shainer R,Reibstein I,Vortmeyer AO,Paidas MJ,Zeira M,Slavin S,Barnea ER

doi

10.1016/j.jns.2011.07.050

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

146-57

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(11)00472-2

journal_volume

312

pub_type

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