Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Jadavji, Nafisa M.; Farr, Tracy D.; Lips, Janet; Khalil, Ahmed A.; Boehm-Sturm, Philipp; Foddis, Marco; Harms, Christoph; F�chtemeier, Martina; Dirnagl, Ulrich

doi:10.1016/j.bbr.2015.01.040

Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells (2023)
Journal Article
Ogrodzinski, L., Platt, S., Goulding, J., Alexander, C., Farr, T. D., Woolard, J., …Kilpatrick, L. E. (2023). Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells. iScience, 26(7), Article 107232. https://doi.org/10.1016/j.isci.2023.107232

E-selectin is expressed on endothelial cells in response to inflammatory cytokines and mediates leukocyte rolling and extravasation. However, studies have been hampered by lack of experimental approaches to monitor expression in real time in living c... Read More about Probing expression of E-selectin using CRISPR-Cas9-mediated tagging with HiBiT in human endothelial cells.

Long-Term Connectome Analysis Reveals Reshaping of Visual, Spatial Networks in a Model With Vascular Dementia Features (2022)
Journal Article
Hall, G. R., Boehm-Sturm, P., Dirnagl, U., Finke, C., Foddis, M., Harms, C., …Farr, T. D. (2022). Long-Term Connectome Analysis Reveals Reshaping of Visual, Spatial Networks in a Model With Vascular Dementia Features. Stroke, 53(5), 1735-1745. https://doi.org/10.1161/STROKEAHA.121.036997

Background: Connectome analysis of neuroimaging data is a rapidly expanding field that offers the potential to diagnose, characterize, and predict neurological disease. Animal models provide insight into biological mechanisms that underpin disease, b... Read More about Long-Term Connectome Analysis Reveals Reshaping of Visual, Spatial Networks in a Model With Vascular Dementia Features.

Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation (2021)
Journal Article
Sorby-Adams, A. J., Learoyd, A. E., Bath, P. M., Burrows, F., Farr, T. D., Leonard, A. V., …Trueman, R. C. (2021). Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation. Journal of Cerebral Blood Flow and Metabolism, 41(12), 3248-3259. https://doi.org/10.1177/0271678X211018901

Hypertension is a leading risk factor for death and dependency after ischaemic stroke. However, administering anti-hypertensive medications post-stroke remains contentious with concerns regarding deleterious effects on cerebral blood flow and infarct... Read More about Glyceryl trinitrate for the treatment of ischaemic stroke: Determining efficacy in rodent and ovine species for enhanced clinical translation.

A pilot of the feasibility and usefulness of an aged obese model for use in stroke research (2021)
Journal Article
Learoyd, A. E., Calmus, R., Cunningham, C. N., England, T. J., Farr, T. D., Fone, K. C., …Trueman, R. C. (2021). A pilot of the feasibility and usefulness of an aged obese model for use in stroke research. Wellcome Open Research, 6, Article 104. https://doi.org/10.12688/wellcomeopenres.16592.1

Background: Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model,... Read More about A pilot of the feasibility and usefulness of an aged obese model for use in stroke research.

UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: questionnaire and workshop proceedings (2020)
Journal Article
McColl, B. W., Allan, S. M., McFall, A., Hietamies, T. M., Bernard, A., Aimable, M., …Quinn, T. J. (2020). UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: questionnaire and workshop proceedings. Journal of Cerebral Blood Flow and Metabolism, 40(7), 1402-1414. https://doi.org/10.1177/0271678x20910552

© The Author(s) 2020. Assessment of outcome in preclinical studies of vascular cognitive impairment (VCI) is heterogenous. Through an ARUK Scottish Network supported questionnaire and workshop (mostly UK-based researchers), we aimed to determine unde... Read More about UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: questionnaire and workshop proceedings.

Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits (2019)
Journal Article
Simanaviciute, U., Ahmed, J., Brown, R. E., Connor-Robson, N., Farr, T. D., Fertan, E., …Grant, R. A. (2020). Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits. Journal of Neuroscience Methods, 331, Article 108532. https://doi.org/10.1016/j.jneumeth.2019.108532

Background : Previous studies have measured whisker movements and locomotion to characterise mouse models of neurodegenerative disease. However, these studies have always been completed in isolation, and do not involve standardized procedures for com... Read More about Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits.

Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable (2019)
Journal Article
McDonald, M. W., Black, S. E., Copland, D. A., Corbett, D., Dijkhuizen, R. M., Farr, T. D., …O’Sullivan, M. J. (2019). Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable. International Journal of Stroke, 14(8), 774-782. https://doi.org/10.1177/1747493019873600

© 2019 World Stroke Organization. Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cogniti... Read More about Cognition in stroke rehabilitation and recovery research: Consensus-based core recommendations from the second Stroke Recovery and Rehabilitation Roundtable.

A Brief Review of Edema-Adjusted Infarct Volume Measurement Techniques for Rodent Focal Cerebral Ischemia Models with Practical Recommendations (2019)
Journal Article
Nouraee, C., Fisher, M., Napoli, M. D., Salazar, P., Farr, T. D., Jafarli, A., & Divani, A. A. (2019). A Brief Review of Edema-Adjusted Infarct Volume Measurement Techniques for Rodent Focal Cerebral Ischemia Models with Practical Recommendations. Journal of Vascular and Interventional Neurology, 10(3), 38-45

Background-Determining cerebral infarction volume is an important part of preclinical studies to determine the benefit of potential therapies on stroke outcome. A well-known problem in determining the actual infarction volume of rodent models is the... Read More about A Brief Review of Edema-Adjusted Infarct Volume Measurement Techniques for Rodent Focal Cerebral Ischemia Models with Practical Recommendations.

Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology (2018)
Journal Article
Horsburgh, K., Wardlaw, J. M., van Agtmael, T., Allan, S. M., Ashford, M. L., Bath, P. M., …Work, L. M. (2018). Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology. Clinical Science, 132(8), https://doi.org/10.1042/CS20171620

Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical resea... Read More about Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology.

Atlas registration for edema-corrected MRI lesion volume in mouse stroke models (2017)
Journal Article
Koch, S., Mueller, S., Foddis, M., Bienert, T., von Elverfeldt, D., Knab, F., …Boehm-Sturm, P. (in press). Atlas registration for edema-corrected MRI lesion volume in mouse stroke models. Journal of Cerebral Blood Flow and Metabolism, https://doi.org/10.1177/0271678X17726635

Lesion volume measurements with magnetic resonance imaging are widely used to assess outcome in rodent models of stroke. In this study, we improved a mathematical framework to correct lesion size for edema which is based on manual delineation of the... Read More about Atlas registration for edema-corrected MRI lesion volume in mouse stroke models.

The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments) (2017)
Journal Article
Percie du Sert, N., Alfieri, A., Allan, S. M., Carswell, H. V., Deuchar, G. A., Farr, T. D., …Macrae, I. M. (in press). The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments). Journal of Cerebral Blood Flow and Metabolism, https://doi.org/10.1177/0271678X17709185

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and ani... Read More about The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments).

Infections up to 76 days after stroke increase disability and death (2017)
Journal Article
Learoyd, A., Woodhouse, L. J., Shaw, L., Sprigg, N., Bereczki, D., Berge, E., …Trueman, R. C. (in press). Infections up to 76 days after stroke increase disability and death. Translational Stroke Research, https://doi.org/10.1007/s12975-017-0553-3

Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke... Read More about Infections up to 76 days after stroke increase disability and death.

Increased homocysteine levels impair reference memory and reducecortical levels of acetylcholine in a mouse model of vascular cognitive impairment (2017)
Journal Article
Dam, K., Füchtemeier, M., Farr, T. D., Boehm-Sturm, P., Foddis, M., Dirnagl, U., …Jadavji, N. M. (2017). Increased homocysteine levels impair reference memory and reducecortical levels of acetylcholine in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 321, https://doi.org/10.1016/j.bbr.2016.12.041

Folates are B-vitamins that are vital for normal brain function. Deficiencies in folates either genetic(methylenetetrahydrofolate reductase, MTHFR) or dietary intake of folic acid result in elevated levelsof homocysteine. Clinical studies have shown... Read More about Increased homocysteine levels impair reference memory and reducecortical levels of acetylcholine in a mouse model of vascular cognitive impairment.

Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment (2017)
Journal Article
Boehm-Sturm, P., Füchtemeier, M., Foddis, M., Mueller, S., Trueman, R. C., Zille, M., …Farr, T. D. (in press). Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment. Stroke, 48(1), https://doi.org/10.1161/STROKEAHA.116.014394

Background and Purpose�Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reli... Read More about Neuroimaging biomarkers predict brain structural connectivity change in a mouse model of vascular cognitive impairment.

Lickometry: a novel and sensitive method for assessing functional deficits in rats after stroke (2017)
Journal Article
Ahmed, J., Dwyer, D. E., Farr, T. D., Harrison, D. J., Dunnett, S. B., & Trueman, R. C. (in press). Lickometry: a novel and sensitive method for assessing functional deficits in rats after stroke. Journal of Cerebral Blood Flow and Metabolism, 37(3), https://doi.org/10.1177/0271678X16684141

The need for sensitive, easy to administer assessments of long-term functional deficits is crucial in pre-clinical stroke research. In the present study, we introduce lickometry (lick microstructure analysis) as a precise method to assess sensorimoto... Read More about Lickometry: a novel and sensitive method for assessing functional deficits in rats after stroke.

Recent progress in translational research on neurovascular and neurodegenerative disorders (2017)
Journal Article
Demuth, H., Dijkhuizen, R. M., Farr, T. D., Gelderblom, M., Horsburgh, K., Iadecola, C., …Boltze, J. (2017). Recent progress in translational research on neurovascular and neurodegenerative disorders. Restorative Neurology and Neuroscience, 35(1), https://doi.org/10.3233/RNN-160690

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundament... Read More about Recent progress in translational research on neurovascular and neurodegenerative disorders.

Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice (2016)
Journal Article
Donath, S., An, J., Lee, S. L. L., Gertz, K., Datwyler, A. L., Harms, U., …Harms, C. (2016). Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice. Journal of Neuroscience, 36(31), 8132-8148. https://doi.org/10.1523/JNEUROSCI.4428-15.2016

The aim of this study was to explore the signaling and neuroprotective effect of transactivator of transcription (TAT) protein transduction of the apoptosis repressor with CARD (ARC) in in vitro and in vivo models of cerebral ischemia in mice. In mic... Read More about Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice.

Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: Tests for long-term assessment (2016)
Journal Article
Trueman, R. C., Diaz, C., Farr, T. D., Harrison, D. J., Fuller, A., Tokarczuk, P. F., …Dunnett, S. B. (2017). Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: Tests for long-term assessment. Journal of Cerebral Blood Flow and Metabolism, 37(4), 1349-1361. https://doi.org/10.1177/0271678X16654921

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits; especially when testing over extended times in milder... Read More about Systematic and detailed analysis of behavioural tests in the rat middle cerebral artery occlusion model of stroke: Tests for long-term assessment.

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity (2016)
Journal Article
Ariza de Schellenberger, A., Kratz, H., Farr, T. D., Löewa, N., Hauptmann, R., Wagner, S., …Schellenberger, E. A. (2016). Labeling of mesenchymal stem cells for MRI with single-cell sensitivity. International Journal of Nanomedicine, 11, 1517-1535. https://doi.org/10.2147/IJN.S101141

Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared... Read More about Labeling of mesenchymal stem cells for MRI with single-cell sensitivity.

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment (2015)
Journal Article
Jadavji, N. M., Farr, T. D., Lips, J., Khalil, A. A., Boehm-Sturm, P., Foddis, M., …Dirnagl, U. (2015). Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment. Behavioural Brain Research, 283, https://doi.org/10.1016/j.bbr.2015.01.040

Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocystei... Read More about Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment.

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