Mapping the molecular fingerprint of stroke: temporal changes in cerebrospinal fluid, brain tissue and serum proteome in a large animal model of stroke.
Speaker: Dr Kirsten Coupland
Senior Lecturer
School of Biomedical Sciences and Pharmacy
The University of Newcastle
Mapping the molecular fingerprint of stroke: temporal changes in cerebrospinal fluid, brain tissue and serum proteome in a large animal model of stroke.
Objective
We characterised the temporal proteome of cerebrospinal fluid (CSF), brain tissue, and serum of a large animal model (Ovis aries) up to 28 days after stroke to identify molecular pathways of damage and repair altered by stroke.
Brief Method
Sheep underwent two-hour temporary middle cerebral artery occlusion with reperfusion, or sham surgery. CSF and serum was collected pre-stroke and at four hours, days one, three, six and 28 after stroke. Brain tissue was collected at day six or 28 after stroke.
Proteins were extracted from tissues and fluids and subsequently digested to peptides and labelled to allow for single-shot mass spectrometry. MS spectra were processed with PD2.5 and analysed using Perseus and Ingenuity Pathway Analysis (IPA).
Key Findings and Conclusions
Changes in pathway activation were largely distinct between CSF, serum, and brain with few showing common activation states across more than one fluid/tissue. Most pathways with a significant alteration in activation at 24 hours post stroke had the inverse activation state by day six after stroke including the complement response, metabolic processes and activation of immune pathways. A pronounced ‘hot spot’ of pathway activation emerged at day six post-stroke, particularly in neuronal and vascular proliferation and migration, indicating a likely pivotal time for post-stroke repair. Finally, no significant differences in pathway activation were seen between the stroke and contralateral hemispheres, implying that most responses to stroke affects the entire brain. These novel findings provide, for the first time, insight into the temporal activation of different pathways after stroke.
Kirsten G. Coupland1,2, David Skerrett-Byrne 1,3,4,5, Merce Fuentès Amell1,2, Heather Murray1,6, Annabel Sorby-Adams7,8, Renée J Turner8, Neil J Spratt1,2,9
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Awabakal Country, Newcastle, Australia.
- Brain Health Program, Hunter Medical Research Institute, Awabakal Country, Newcastle, Australia.
- Reproductive and Family Health Program, Hunter Medical Research Institute, Awabakal Country, Newcastle, Australia.
- Institute of Experimental Genetics, Helmholtz Zentrum Munchen, German Research Centre for Environmental Health, Neuherberg, Germany.
- German Center for Diabetes Research (DZD) Neuherberg, Germany.
- Precision Medicine and Health Research Program, University of Newcastle, Awabakal Country, Newcastle Australia.
- Department of Neurology and the Centre for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
- School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Kaurna Country, Adelaide, South Australia, Australia.
- Hunter New England Local Health District, Awabakal Country, Newcastle, Australia.
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