Low sulfated heparins target multiple proteins for central nervous system repair.

With all this good stuff occurring with low sulfated heparins whom will your doctors and stroke hospital contact to get further research done creating a stroke protocol out of this? I bet they will incompetently DO NOTHING because it is easier to wait for SOMEONE ELSE TO SOLVE THE PROBLEM?    

astrogliosis defined here.

Low sulfated heparins target multiple proteins for central nervous system repair.

S. C. Barnett¹, G. Mcanney¹, M. Mcgrath¹, C. Bavington², J. Turnbull³

¹ University of glasgow, , Institute of Infection, Immunity and Inflammation, glasgow, United Kingdom
² GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, United Kingdom
³ University of Liverpool, Institute of Integrative Biology, Liverpoll, United Kingdom

Content
The poor repair that follows CNS injury leads to permanent disabilities for which effective treatments are limited. After injury, the glial scar that forms is one factor-preventing repair. Previously, we demonstrated that heparins modified by selective desulphation (mHeps) reduce features of astrogliosis. mHeps are a class of glycomolecules with structural similarities to resident heparan sulfates (HS) that comprise repeating disaccharide units with variable sulphation patterns. HS are key modulators of cell signalling by both sequestering ligands (including chemokine/cytokines) in the ECM and acting as cofactors in the formation of ligand-receptor complexes. To assess whether mHeps would affect other neural cell types, we treated mixed neural cultures to determine their effect on myelination and neurite outgrowth. Using myelinating co-cultures (MC) we demonstrate that the degree and positions of the sulphate moieties on mHeps are crucial for their biological effects. Specifically, monosulphated compounds at C2 and N positions have the greatest effect on promoting neurite outgrowth and (re)myelination, whereas, highly sulphated heparin isoforms had detrimental effects. No effects of mHeps were seen on naturally developing MCs (MC-Dev), suggesting that the beneficial/detrimental effects of mHeps were due to interactions with factors secreted during the injury process. Comparison of the secreted factors from the various MCs illustrated differences in the profile of chemokines/cytokine released. To identify factors that interact with the most effective mHep (mHep7) we carried out a TMT-LC-MS analysis on affinity purified conditioned media. Numerous factors were identified including amyloid beta A4, further investigation established the ability of amyloid beta peptide (1-42) to inhibit myelination, this effect could be overcome with co-treatment of mHep7. We propose that desulphated mHeps may be novel therapeutics for CNS repair.
Acknowledgement
The work was supported by a project grant ETM/439 from CSO (MM) and a PhD studentship (PhD‐769‐2014) from Medical Research Scotland (GM), and the Wellcome Trust (202789/Z/16/Z).