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

Lola Weiss, Reuven Or, Richard C. Jones, Ravi Amunugama, Lellean Jebailey, Sivakumar Ramu, Steven A. Bernstein, Zhanna Yekhtin, Osnat Almogi-Hazan, Reut Shainer, Israel Reibstein, Alexander O. Vortmeyer, Michael J. Paidas, Michael Zeira, Shimon Slavin, Eytan R. Barnea

Research output: Contribution to journalArticle

37 Scopus citations

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: 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.

Original languageEnglish (US)
Pages (from-to)146-157
Number of pages12
JournalJournal of the Neurological Sciences
Volume312
Issue number1-2
DOIs
StatePublished - Jan 15 2012
Externally publishedYes

Keywords

  • Neurogenesis
  • Neuroinflammation
  • Paralysis
  • Preimplantation Factor
  • Regression

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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  • Cite this

    Weiss, L., Or, R., Jones, R. C., Amunugama, R., Jebailey, L., Ramu, S., Bernstein, S. A., Yekhtin, Z., Almogi-Hazan, O., Shainer, R., Reibstein, I., Vortmeyer, A. O., Paidas, M. J., Zeira, M., Slavin, S., & Barnea, E. R. (2012). Preimplantation Factor (PIF*) reverses neuroinflammation while promoting neural repair in EAE model. Journal of the Neurological Sciences, 312(1-2), 146-157. https://doi.org/10.1016/j.jns.2011.07.050