Karen Horsburgh received a BSc in Pharmacology and a PhD in Neuroscience at the University of Glasgow. After two years at an Alzheimer’s Disease Institute (Dept. of Neuroscience, University of California, San Diego) she returned to the University of Glasgow and awarded a SHERT/Mrs Jean Baxter Research Fellowship. In May 2002 she received a Wellcome Trust University Award and moved to the University of Edinburgh. She currently holds the position of Professor of Neuroscience. She has served on the research panels of Medical Research Scotland and Alzheimer’s Research UK. Karen is lead co-ordinator of an Alzheimer’s Society doctoral training programme and an Alzheimer’s Research UK network in Scotland. She is currently a member of the MRC Dementia Platform UK Vascular Experimental Medicine committee.
Our research investigates the mechanisms underlying cognitive decline relevant to Cerebral Vascular disease and Alzheimer’s disease (AD) with the aim to identify novel targets for therapeutic strategies to slow the rate of cognitive decline and prevent dementia. Chronic cerebrovascular pathology is a leading cause of dementia, and arguably represents the most important modifiable risk factor for Alzheimer's disease. Despite this importance, the mechanisms and pathways contributing to vascular cognitive impairment have largely remained elusive. Central to the pathophysiology of cerebral microvascular disease is likely to be disruption of the finely tuned interplay between the cells in the neurovascular unit (NVU) that form an essential bridge between blood and neuron. The molecular basis of NVU dysfunctions that lead to cerebral microvascular disease and dementia, and the molecular signals underlying cross-talk between different cell types of the NVU, are still poorly understood and are a focus of our research in experimental models and human post-mortem tissues. Our current work is focussed on mechanisms related to endothelial cell activation and microvascular inflammation in models of vascular cognitive impairment.
- Juraj Koudelka, Post-doctoral Researcher
- Nela Fialova, MSc Student
Our current work is funded by:
Dr.Jill Fowler (CNR, University of Edinburgh)
Dr.Barry McColl (Roslin Institute)
Dr. Maurits Jansen (CVS, University of Edinburgh)
Dr. Adriana Tavares (CVS, University of Edinburgh)
Prof. Ian Marshall (CCBS, University of Edinburgh)
Prof. Joanna Wardlaw (CCBS, University of Edinburgh)
Prof. Raj Kalaria (University of Newcastle)
Dr. Masafumi Ihara (Kyoto University)
Prof. Ajay Shah (Kings College London)
Selected Recent Publications
- Chen A, Akinyemi RO, Hase Y, Firbank MJ, Ndung'u MN, Foster V, Craggs LJ, Washida K, Okamoto Y, Thomas AJ, Polvikoski TM, Allan LM, Oakley AE, O'Brien JT, Horsburgh K, Ihara M, Kalaria RN. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia.Brain. 2015 Dec 14. pii: awv328.
- Kitamura A, Saito S, Maki T, Oishi N, Ayaki T, Hattori Y, Yamamoto Y, Urushitani M, Kalaria RN, Fukuyama H, Horsburgh K, Takahashi R, Ihara M. Gradual cerebral hypoperfusion in spontaneously hypertensive rats induces slowly evolving white matter abnormalities and impairs working memory. J Cereb Blood Flow Metab. 2015 Oct 13. pii: 0271678X15606717.
- Holland PR, Searcy JL, Salvadores N, Scullion G, Chen G, Lawson G, Scott F, Bastin ME, Ihara M, Kalaria R, Wood ER, Smith C, Wardlaw JM, Horsburgh K. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease. J Cereb Blood Flow Metab. 2015. 35(6):1005-14 doi: 10.1038/jcbfm.2015.12.
- Holland PR, Pannozzo MA, Bastin ME, McNeilly AD, Ferguson KJ, Caughey S, Jansen MA, Merrifield GD, Marshall I, Mullins JJ, Wardlaw JM, Sutherland C, Horsburgh K. Hypertension fails to disrupt white matter integrity in young or aged Fisher (F44) Cyp1a1Ren2 transgenic rats. J Cereb Blood Flow Metab. 2015 35(2):188-92. doi: 10.1038/jcbfm.2014.201. Epub 2014 Nov 19.
- McQueen J, Reimer MM, Holland PR, Horsburgh K. (2014) Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion Plos One 9(2):e87227. doi: 10.1371/journal.pone.0087227.
- Searcy JL,, Le Bihan T, Salvadores N, McCulloch J, Horsburgh K. (2014) Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice. Plos One 9(2):e89970. doi: 10.1371/journal.pone.0089970.
- Pannozzo MA,. Holland PR, Scullion G, Talbot R, Mullins JJ, Horsburgh K (2013)Controlled hypertension induces cerebrovascular and gene alterations in Cyp1a1-ren2 transgenic rats. J. Am. Soc Hypertension 7(6):411-9. doi: 10.1016/j.jash.2013.07.011.
- Martel MA, Ryan TJ, Bell KF, Fowler JH, McMahon A, Al-Mubarak B, Komiyama NH, Horsburgh K, Kind PC, Grant SG, Wyllie DJ, Hardingham GE. (2012) The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults. Neuron. 74(3):543-56.
Key Earlier Publications
- James R, Searcy JL, Le Bihan T, Martin S, Roses A, Gliddon CM, Deighton RF, Kerr LE, McCulloch J, Horsburgh K. (2012) Genotype dependant differences in the mitochondrial proteomic response to an ischaemic challenge. JCBFM 32(1):164-76
- Reimer MM, McQueen J, Searcy, Zonta B, Desmazieres A, Smith J, Gliddon C, ScullionG, Wood E, Herzyk P, Brophy P, McCulloch J, Horsburgh K. (2011) Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion. J Neurosci 31(49):18185-94.
- Bell KFS, Al-Mubarak B, Fowler JH, Baxter PS, Tsujita T, Chowdhry S, Horsburgh K, Hayes JD, Hardingham GE (2011) Mild oxidative stress activates Nrf2 in astrocytes which contributes to neuroprotective ischemic preconditioning Proc Natl Acad Sci U S A. 108(1):E1-2.
Holland PR, Bastin ME, Jansen MA, Merrifield GD, Coltman RB, Scott F, Nowers H, Khallout K, Marshall I, Wardlaw J, Deary IJ, McCulloch J, Horsburgh K. (2011) MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice. Neurobiol Aging 32(12):2325.e1-6.
Coltman R, Spain A, Tsenkina Y, Fowler JH, Smith J, Allerhand M, Scott F, Kalaria RN, Ihara M, Daumas S, Deary IJ, Wood E, McCulloch J, Horsburgh K. (2011) Spatial memory in mice remains intact despite widespread white matter pathology Neurobiol Aging 32(12):2324.e7-2324.e12.
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