Alastair Buchan

Alastair Buchan
University of Oxford | OX · Division of Medical Sciences

DSc (Oxford)

About

405
Publications
100,796
Reads
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31,652
Citations
Citations since 2016
72 Research Items
14460 Citations
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Additional affiliations
October 2008 - present
University of Oxford
Position
  • DEAN OF MEDICINE and Head of Division
July 2006 - July 2009
NIHR Oxford Biomedical Research
NIHR Oxford Biomedical Research
Position
  • Managing Director
December 2004 - present
University of Oxford
Position
  • Professor (Full)

Publications

Publications (405)
Preprint
Full-text available
Hyperpolarized carbon-13 MRI is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a model-free formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel model-free perfusion and metabolic clearance rate (MCR) model in pre-cl...
Preprint
Full-text available
Hyperpolarized carbon-13 MRI is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a model-free formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel model-free perfusion and metabolic clearance rate (MCR) model in pre-cl...
Article
Introduction: Stroke is a global leading cause of adult disability and death. Hypothermia is the most potent neuroprotectant preclinically. It acts broadly upon the pathophysiological mechanisms of ischemia-induced injury. Clinical trials using physical cooling, which triggers compensatory thermogenesis, have failed. Activation of hypothalamic A1...
Article
Introduction: Leptomeningeal collateral flow is a strong predictor of stroke outcome. Enhancing collateral flow is an appealing therapeutic approach. However, previous attempts to enhance collateral flow with vasodilators have failed, due to systemic hypotension and cerebrovascular steal from the penumbra. We have shown that during experimental str...
Article
Full-text available
Brain health is essential for physical and mental health, social well‐being, productivity, and creativity. Current neurological research focuses mainly on treating a diseased brain and preventing further deterioration rather than on developing and maintaining brain health. The pandemic has forced a shift toward virtual working environments that acc...
Article
The goal of effective neuroprotection in acute ischemic stroke remains elusive. Despite decades of experimental preclinical and clinical experience with innumerable agents, no strategy has proven to be beneficial in humans. As endovascular therapies mature and approach the limits of speed and efficacy, neuroprotection will become the next frontier...
Article
Reperfusion therapy with intravenous alteplase and endovascular therapy are effective treatments for selected patients with acute ischemic stroke. Guidelines for treatment are based upon randomized trials demonstrating substantial treatment effects for highly selected patients based on time from stroke onset and imaging features. However, patients...
Article
Background and Purpose The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers. Methods This forum brough...
Article
Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke treatments. At STAIR XI, particip...
Article
Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to...
Article
Full-text available
Objective Scientific authorship is a vital marker of achievement in academic careers and gender equity is a key performance metric in research. However, there is little understanding of gender equity in publications in biomedical research centres funded by the National Institute for Health Research (NIHR). This study assesses the gender parity in s...
Article
Key messages: Gender equity in research can contribute to social progress, scientific workforce sustainability, and the quality of science. Research funders can be critical actors in advancing gender equity through policy interventions and funding incentives. Linking NIHR funding to Athena SWAN gender equality action plans has been associated wi...
Article
Full-text available
Background The underrepresentation of women in academic medicine at senior level and in leadership positions is well documented. Biomedical Research Centres (BRC), partnerships between leading National Health Service (NHS) organisations and universities, conduct world class translational research funded by the National Institute for Health Research...
Article
Full-text available
Background and purpose Rapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. However, the mechanism of rapamycin-induced neuroprotection is still being explored. Our aims were to determine if rapamycin improved leptomeningeal collateral perfusion, to determi...
Article
Full-text available
Age-related neuronal dysfunction can be overcome by circulating factors present in young blood. Growth differentiation factor-11 (GDF-11), a systemic factor that declines with age, can reverse age-related dysfunction in brain, heart and skeletal muscle. Given that age increases susceptibility to stroke, we hypothesized that GDF-11 may be directly p...
Article
Acute stroke treatment requires clear protocols to rapidly triage patients – using appropriate investigations – for endovascular thrombectomy and intravenous thrombolysis. Computed tomography (CT) excludes haemorrhage, CT angiography locates the occluded vessel, and perfusion magnetic resonance imaging identifies viable tissue. An organized approac...
Article
Introduction: The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of c...
Preprint
Full-text available
Objective: Scientific authorship is a vital marker of success in academic careers and gender equity is a key performance metric in research. However, there is little understanding of gender equity in publications in biomedical research centres funded by the National Institute for Health Research (NIHR). This study assesses the gender parity in scie...
Preprint
Full-text available
Background: The underrepresentation of women in academic medicine at senior level and in leadership positions is well documented. In the United Kingdom, the National Institute for Health Research (NIHR) announced that eligibility for funding for Biomedical Research Centres (BRCs) required at least Silver award status of the Athena SWAN Charter. How...
Article
Background and Purpose: In the era of thrombectomy, there is evidence suggesting that successful recanalization is not always accompanied by complete reperfusion, the so called “no-reflow phenomenon”. Given the importance of reperfusion as a predictor of stroke outcome, this represents a potential target for stroke therapy. Rapamycin, a clinically...
Article
Full-text available
Creating a more supportive and inclusive university culture: a mixed-methods interdisciplinary comparative analysis of medical and social sciences at the University of Oxford ABSTRACT Results of two C-Change surveys of 4997 faculty and staff in medical and social sciences are analysed quantitatively and qualitatively and presented with illustrative...
Article
Introduction Hamartin, a component of the tuberous sclerosis complex (TSC) that actively inhibits the mammalian target of rapamycin (mTOR), may mediate the endogenous resistance of Cornu Ammonis 3 (CA3) hippocampal neurons following global cerebral ischemia. Pharmacological compounds that selectively inhibit mTOR may afford neuroprotection followin...
Article
Full-text available
Background: Promoting Responsible Research and Innovation (RRI) is a major strategy of the "Science with and for Society" work program of the European Union's Horizon 2020 Framework Programme for Research and Innovation. RRI aims to achieve a better alignment of research and innovation with the values, needs, and expectations of society. The RRI s...
Article
Full-text available
Background While the European Union is striving to become the ‘Innovation Union’, there remains a lack of quantifiable indicators to compare and benchmark regional innovation clusters. To address this issue, a HealthTIES (Healthcare, Technology and Innovation for Economic Success) consortium was funded by the European Union’s Regions of Knowledge i...
Article
Full-text available
Background: Amplifying endogenous neuroprotective mechanisms is a promising avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a serine/threonine kinase regulating cell proliferation, cell survival, protein synthesis, and autophagy. Animal studies investigating the effect of rapamycin on mTOR inhibition following cerebr...
Article
Full-text available
The significant morbidity that accompanies stroke makes it one of the world's most devastating neurological disorders. Currently, proven effective therapies have been limited to thrombolysis and thrombectomy. The window for the administration of these therapies is narrow, hampered by the necessity of rapidly imaging patients. A therapy that could e...
Cover Page
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Preprint
Full-text available
BACKGROUND Promoting Responsible Research and Innovation (RRI) is a major strategy of the “Science with and for Society” work programme of the European Union’s Horizon 2020 Framework Programme for Research and Innovation. RRI aims to achieve a better alignment of research and innovation with the values, needs, and expectations of society. The RRI s...
Conference Paper
Model-based analysis of CEST MRI is a robust quantitative method, however, the lengthy acquisition and processing times make it less clinically feasible. It has recently been proposed that partial acquisition of Z-spectra provides a faster approach, but at the cost of increased variability and large alterations in baseline Amide Proton Transfer (AP...
Chapter
Oxidative stress is a major mechanism responsible for damage in ischemic stroke. Other than tissue plasminogen activator and antiplatelet agents, no pharmacological interventions have been translated into an effective treatment for stroke. As yet, there have been no unequivocally successful clinical applications of antioxidants to scavenge reactive...
Article
Full-text available
Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs)...
Article
Endovascular mechanical thrombectomy (MT) for the treatment of acute stroke due to large vessel occlusion has evolved significantly with the publication of multiple positive thrombectomy trials. MT is now a recommended treatment for acute ischemic stroke. Mechanical thrombectomy is associated with a number of intra-procedural or post-operative comp...
Article
Full-text available
Background Cornu ammonis 3 (CA3) hippocampal neurons are resistant to global ischemia, whereas cornu ammonis (CA1) 1 neurons are vulnerable. Hamartin expression in CA3 neurons mediates this endogenous resistance via productive autophagy. Neurons lacking hamartin demonstrate exacerbated endoplasmic reticulum stress and increased cell death. We inves...
Article
Acute ischaemic stroke accounts for 6.5 million deaths per year, and by 2030 will result in the annual loss of over 200 million disability-adjusted life years globally. There have been considerable recent advances in the gold standard of acute ischaemic stroke treatment, some aspects of which-aspirin to prevent recurrence, and treating patients in...
Article
Full-text available
Background and purpose: Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. Methods: EVs were quantified and ana...
Conference Paper
Full-text available
Model-based analysis of APT MRI has been shown to quantitatively outperform conventional approaches such as asymmetry analysis. However clinical application is hindered by slow acquisition of whole z-spectra, and processing times. Here, we demonstrate that by using only a subset of frequency offsets, acquisition and processing time can be reduced b...
Article
Full-text available
Significance statement: Neuronal activity leads to the generation of CO2, which has previously been shown to evoke cerebral blood flow (CBF) increases via the release of the vasodilator PgE2 We demonstrate that hypercapnia (increased CO2) evokes increases in astrocyte calcium signaling which in turn stimulates COX-1 activity and generates downstre...
Article
Full-text available
Objective: To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome. Methods: We included stud...
Chapter
Ischaemic stroke is a major global cause of disability and death, yet the therapeutic options currently available for stroke are very limited. The only effective acute treatments of ischemic stroke revolve around restoring patency to the occluded artery through degradation (intravenous thrombolysis) or mechanical removal of the clot [Int J Stroke 1...
Article
Full-text available
Background Women’s participation in medicine and the need for gender equality in healthcare are increasingly recognised, yet little attention is paid to leadership and management positions in large publicly funded academic health centres. This study illustrates such a need, taking the case of four large European centres: Charité – Universitätsmediz...
Article
Background: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an established 10-point quantitative topographic computed tomography scan score to assess early ischemic changes. We performed a non-inferiority trial between the e-ASPECTS software and neuroradiologists in scoring ASPECTS on non-contrast enhanced computed tomograp...
Article
Full-text available
Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely...
Article
Full-text available
Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science...
Article
Pericytes are contractile vascular mural cells overlying capillary endothelium, and they have been implicated in a variety of functions including regulation of cerebral blood flow. Recent work has suggested that both in vivo and ex vivo, ischaemia causes pericytes to constrict and die, which has implications for microvascular reperfusion. Assessing...
Article
Cerebrovascular disease can be devastating for patients and their families, but much can be done to attenuate cerebral damage and reduce disability. Active intervention is in three phases: acute therapy, rehabilitation and secondary prevention. Thrombolysis within 4.5 hours of symptom onset substantially reduces morbidity from ischaemic stroke with...
Article
Women are under-represented in academic medicine. We reviewed the empirical evidence focusing on the reasons for women's choice or rejection of careers in academic medicine. Using a systematic search, we identified 52 studies published between 1985, and 2015. More than half had methodological limitations and most were from North America. Eight main...