Mast cell dependent pathology may be mediated by endothelin-1, matrixmettaloproteinase-9 and endoglin, after transient middle cerebral artery occlusion.

Craig Martin McKittrick, Catherine Lawrence, Hilary Carswell

Research output: Contribution to conferenceSpeech

Abstract

Our previous work showed that genetic mast cell ablation and pharmacological stabilisation significantly reduce oedema, BBB permeability and neutrophil recruitment during the acute phase of reperfusion in experimental stroke.

Activated mast cells release pre-formed tumour necrosis factor-alpha (TNF-α), other cytokines, chemokines, proteases and vasoactive mediators, among others. Therefore, we investigated the expression of an array of proteins in the brain, which may be produced by mast cells directly or induced indirectly in other cell types by the action of mast cells. Additionally, we measured TNF-α concentration. Finally, we measured regional cerebral blood flow to detect any differences in perfusion between the C57BL6 wild type and mast cell deficient C57BL6 Kitw-sh/w-sh mouse strains.

Mice underwent 20 minutes tMCAo, with 5 minutes of reperfusion or 45 minutes tMCAo followed by 45 minutes of reperfusion. Blood flow was monitored throughout using laser Doppler flowmetry. Sham animals underwent the same procedure but did not have the MCA occluded. At termination, ipsilateral hemispheres were analysed by ELISA to determine TNF-α concentration. A proteome profiler array identified the relative expression of 53 proteins related to angiogenesis, within brain homogenates.

At both time points analysed there was no difference in TNF-α concentration in serum and tissue homogenates or in regional blood flow during the occlusion period, between all groups. Also, 20 minutes tMCAo induce similar protein expression profiles in both mouse strains. However, after 45 minutes tMCAo, endothlin-1, matrixmettaloproteinase-9 and endoglin were all expressed in wild type, but were absent in mast cell deficient mice.
Original languageEnglish
Publication statusPublished - 2 Feb 2013
EventScottish Cardiovascular Forum 2013 - University of Strathclyde, Glasgow, United Kingdom
Duration: 2 Feb 2013 → …

Conference

ConferenceScottish Cardiovascular Forum 2013
CountryUnited Kingdom
CityGlasgow
Period2/02/13 → …

Keywords

  • mast cell
  • cerebral artery occlusion

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