Therapeutic Effects of Systemic Administration of the Novel RANKL-Modified Peptide, MHP1, for Ischemic Stroke in Mice

BioMed Research International
Munehisa ShimamuraRyuichi Morishita

Abstract

Microglial healing peptide 1, "MHP1", is a newly developed synthetic peptide composed of the DE and a part of the EF loop of the receptor activator of nuclear factor-кB (NFκB) ligand (RANKL). Our previous report demonstrated that MHP1 significantly inhibits Toll-like receptor (TLR) 2- and 4-induced inflammation in microglia/macrophages through RANK signaling without osteoclast activation. However, its inhibitory effects on ischemic stroke when administered intravenously have not been clarified. First, we examined whether MHP1 could penetrate the brain parenchyma. Intravenous injection of FITC-conjugated MHP1 demonstrated that MHP1 could cross the blood-brain-barrier in peri-infarct regions, but not in intact regions. Because MHP1 in the parenchyma was reduced at 60 minutes after injection, we speculated that continuous injection was necessary to achieve the therapeutic effects. To check the possible deactivation of MHP1 by continuous injection, the anti-inflammatory effects were checked in MG6 cells after incubation in 37°C for 24 hours. Although the inhibitory effects for IL6 and TNFα were reduced compared to nonincubated MHP1, its anti-inflammatory efficacy remained, indicating that continuous administration with pump was pos...Continue Reading

References

Jun 1, 2000·Journal of the Neurological Sciences·Y SatoK Oizumi
Oct 3, 2001·The Journal of Clinical Investigation·J LamD H Fremont
May 4, 2002·Stroke; a Journal of Cerebral Circulation·Kenneth E S PooleElizabeth A Warburton
Jun 16, 2004·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Kenneth E S PooleJonathan Reeve
Jul 24, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Takato AbeCostantino Iadecola
Aug 8, 2009·Stroke; a Journal of Cerebral Circulation·Sander PouwelsFrank de Vries
Jun 24, 2010·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·S Ferrari-Lacraz, S Ferrari
Mar 1, 2011·Clinical Immunology : the Official Journal of the Clinical Immunology Society·David BreaJosé Castillo
Jul 9, 2011·Nature Medicine·Costantino Iadecola, Josef Anrather
Jan 6, 2012·Journal of Korean Medical Science·Myung Eun ChungJoo Hyun Park
Aug 30, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·William M Pardridge
Jul 23, 2013·Stroke; a Journal of Cerebral Circulation·Edith KohlerDavid Blacker
May 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Munehisa ShimamuraRyuichi Morishita
May 27, 2015·Journal of Pharmaceutical Sciences·Emilien FolzerAtanas V Koulov
Feb 17, 2017·PloS One·Zamir MeraliAndrea Kassner

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Methods Mentioned

BETA
Enzyme-Linked Immunosorbent Assay
ELISA
confocal microscopy
Reverse Transcription Polymerase Chain Reaction
PCRs

Software Mentioned

GraphPad Prism
Unique Acquisition

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