Premium
The melanocortin receptor system in mediating anti‐inflammatory protection following cerebral ischemia reperfusion injury
Author(s) -
holloway paul M,
getting stephen j,
gavins felicity
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.680.23
Subject(s) - melanocortin , medicine , microcirculation , ischemia , neuroprotection , agonist , reperfusion injury , intravital microscopy , inflammation , stroke (engine) , pharmacology , receptor , melanocortin receptor , neuroscience , biology , mechanical engineering , engineering
The melanocortin receptor system (MRS) provides an attractive target for the treatment of stroke, due to their ability to initiate anti‐inflammatory and neuroprotective pathways. However, the relative contribution of the receptors that mediate these effects (MC1 MC3 and MC4) have yet to be determined. This current work aims to assess the therapeutic potential of targeting the MRS for treatment of stroke. The bilateral common carotid artery occlusion (BCCAo) mouse model of global stroke was utilised in conjunction with intravital microscopy, to quantify the neuro‐inflammatory response through real time visualisation of leukocyte recruitment in the cerebral microcirculation. BCCAo induced significant increases in leukocyte rolling and adhesion in the cerebral microcirculation. Treatment with the pan receptor agonist α‐MSH significantly reduced the ischemia‐reperfusion induced leukocyte recruitment. Antagonism of MC3 and MC4 using SHU9119 failed to abrogate the anti‐inflammatory effects of α‐MSH early in reperfusion (40 min), but was able to blunt the effects of α‐MSH by 2h. These results suggest that in the early stages of reperfusion, MC1 activation may be of particular importance in mediating protection within the cerebral microcirculation. However as the inflammatory reaction progresses the role of MC3 may become more prominent. This work was funded by the British Heart Foundation