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4. Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol

Author

Stovell, Matthew G., primary, Ruetten, Pascal P.R., additional, Tozer, Daniel J., additional, Launey, Yoann, additional, Zimphango, Chisomo, additional, Thelin, Eric P., additional, Lupson, Victoria C., additional, Giorgi-Coll, Susan, additional, Carpenter, T. Adrian, additional, Mada, Marius O., additional, Jalloh, Ibrahim, additional, Helmy, Adel, additional, Wilson, Mark H., additional, Graves, Martin J., additional, Menon, David K., additional, Carpenter, Keri L.H., additional, and Hutchinson, Peter J., additional

Published
2024
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5. Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Author

Khellaf, Abdelhakim, Garcia, Nuria Marco, Tajsic, Tamara, Alam, Aftab, Stovell, Matthew G, Killen, Monica J, Howe, Duncan J, Guilfoyle, Mathew R, Jalloh, Ibrahim, Timofeev, Ivan, Murphy, Michael P, Carpenter, T Adrian, Menon, David K, Ercole, Ari, Hutchinson, Peter J, Carpenter, Keri LH, Thelin, Eric P, and Helmy, Adel

Published
2022
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8. sj-pdf-1-jcb-10.1177_0271678X231173584 - Supplemental material for High-physiological and supra-physiological 1,2-13C2 glucose focal supplementation to the traumatised human brain

Author

Stovell, Matthew G, Howe, Duncan J, Thelin, Eric P, Jalloh, Ibrahim, Helmy, Adel, Guilfoyle, Mathew R, Grice, Peter, Mason, Andrew, Giorgi-Coll, Susan, Gallagher, Clare N, Murphy, Michael P, Menon, David K, Carpenter, T Adrian, Hutchinson, Peter J, and Carpenter, Keri LH

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231173584 for High-physiological and supra-physiological 1,2-13C2 glucose focal supplementation to the traumatised human brain by Matthew G Stovell, Duncan J Howe, Eric P Thelin, Ibrahim Jalloh, Adel Helmy, Mathew R Guilfoyle, Peter Grice, Andrew Mason, Susan Giorgi-Coll, Clare N Gallagher, Michael P Murphy, David K Menon, T Adrian Carpenter, Peter J Hutchinson and Keri LH Carpenter in Journal of Cerebral Blood Flow & Metabolism

Published
2023
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12. High-physiological and supra-physiological 1,2- 13 C2 glucose focal supplementation to the traumatised human brain.

Author

Stovell, Matthew G, Howe, Duncan J, Thelin, Eric P, Jalloh, Ibrahim, Helmy, Adel, Guilfoyle, Mathew R, Grice, Peter, Mason, Andrew, Giorgi-Coll, Susan, Gallagher, Clare N, Murphy, Michael P, Menon, David K, Carpenter, T Adrian, Hutchinson, Peter J, and Carpenter, Keri LH

Abstract

How to optimise glucose metabolism in the traumatised human brain remains unclear, including whether injured brain can metabolise additional glucose when supplied. We studied the effect of microdialysis-delivered 1,2-13C2 glucose at 4 and 8 mmol/L on brain extracellular chemistry using bedside ISCUS flex, and the fate of the 13C label in the 8 mmol/L group using high-resolution NMR of recovered microdialysates, in 20 patients. Compared with unsupplemented perfusion, 4 mmol/L glucose increased extracellular concentrations of pyruvate (17%, p = 0.04) and lactate (19%, p = 0.01), with a small increase in lactate/pyruvate ratio (5%, p = 0.007). Perfusion with 8 mmol/L glucose did not significantly influence extracellular chemistry measured with ISCUS flex, compared to unsupplemented perfusion. These extracellular chemistry changes appeared influenced by the underlying metabolic states of patients' traumatised brains, and the presence of relative neuroglycopaenia. Despite abundant 13C glucose supplementation, NMR revealed only 16.7% 13C enrichment of recovered extracellular lactate; the majority being glycolytic in origin. Furthermore, no 13C enrichment of TCA cycle-derived extracellular glutamine was detected. These findings indicate that a large proportion of extracellular lactate does not originate from local glucose metabolism, and taken together with our earlier studies, suggest that extracellular lactate is an important transitional step in the brain's production of glutamine. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension

Author

Yang, Peiran, Read, Cai, Kuc, Rhoda E., Buonincontri, Guido, Southwood, Mark, Torella, Rubben, Upton, Paul D., Crosby, Alexi, Sawiak, Stephen J., Carpenter, T. Adrian, Glen, Robert C., Morrell, Nicholas W., Maguire, Janet J., and Davenport, Anthony P.

Published
2017
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16. Consensus statement from the 2014 International Microdialysis Forum

Author

Hutchinson, Peter J., Jalloh, Ibrahim, Helmy, Adel, Carpenter, Keri L. H., Rostami, Elham, Bellander, Bo-Michael, Boutelle, Martyn G., Chen, Jeff W., Claassen, Jan, Dahyot-Fizelier, Claire, Enblad, Per, Gallagher, Clare N., Helbok, Raimund, Hillered, Lars, Le Roux, Peter D., Magnoni, Sandra, Mangat, Halinder S., Menon, David K., Nordström, Carl-Henrik, O’Phelan, Kristine H., Oddo, Mauro, Perez Barcena, Jon, Robertson, Claudia, Ronne-Engström, Elisabeth, Sahuquillo, Juan, Smith, Martin, Stocchetti, Nino, Belli, Antonio, Carpenter, T. Adrian, Coles, Jonathan P., Czosnyka, Marek, Dizdar, Nil, Goodman, J. Clay, Gupta, Arun K., Nielsen, Troels H., Marklund, Niklas, Montcriol, Ambroise, O’Connell, Mark T., Poca, Maria A., Sarrafzadeh, Asita, Shannon, Richard J., Skjøth-Rasmussen, Jane, Smielewski, Peter, Stover, John F., Timofeev, Ivan, Vespa, Paul, Zavala, Elizabeth, and Ungerstedt, Urban

Published
2015
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21. Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Author

Khellaf, Abdelhakim, primary, Garcia, Nuria Marco, additional, Tajsic, Tamara, additional, Alam, Aftab, additional, Stovell, Matthew G, additional, Killen, Monica J, additional, Howe, Duncan J, additional, Guilfoyle, Mathew R, additional, Jalloh, Ibrahim, additional, Timofeev, Ivan, additional, Murphy, Michael P, additional, Carpenter, T Adrian, additional, Menon, David K, additional, Ercole, Ari, additional, Hutchinson, Peter J, additional, Carpenter, Keri LH, additional, Thelin, Eric P, additional, and Helmy, Adel, additional

Published
2021
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24. Mitochondrial dysfunction in patients with primary congenital insulin resistance

Author

Sleigh, Alison, Raymond-Barker, Philippa, Thackray, Kerrie, Porter, David, Hatunic, Mensud, Vottero, Alessandra, Burren, Christine, Mitchell, Catherine, McIntyre, Martin, Brage, Soren, Carpenter, T. Adrian, Murgatroyd, Peter R., Brindle, Kevin M., Kemp, Graham J., O'Rahilly, Stephen, Semple, Robert K., and Savage, David B.

Subjects
Physiological aspects, Glucose -- Physiological aspects, Skeletal muscle -- Physiological aspects, Glucose metabolism -- Physiological aspects, Type 2 diabetes -- Physiological aspects, Insulin resistance -- Physiological aspects, Cholesterol -- Physiological aspects, Genetic disorders -- Physiological aspects, Dextrose -- Physiological aspects, Muscles -- Physiological aspects
Abstract

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic [...]

Published
2011
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26. Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications

Author

Newcombe, Virginia F.J., Williams, Guy B., Scoffings, Daniel, Cross, Justin, Carpenter, T. Adrian, Pickard, John D., and Menon, David K.

Subjects
Persistent vegetative state -- Physiological aspects, Persistent vegetative state -- Diagnosis, Persistent vegetative state -- Care and treatment, Persistent vegetative state -- Research, Neuroimaging -- Methods, Neuroimaging -- Analysis, Stroke (Disease) -- Patient outcomes, Stroke (Disease) -- Research, Brain -- Injuries, Brain -- Patient outcomes, Brain -- Research, Health, Psychology and mental health
Published
2010

27. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis

Author

Semple, Robert K., Sleigh, Alison, Murgatroyd, Peter R., Adams, Claire A., Bluck, Les, Jackson, Sarah, Vottero, Alessandra, Kanabar, Dipak, Charlton-Menys, Valentine, Durrington, Paul, Soos, Maria A., Carpenter, T. Adrian, Lomas, David J., Cochran, Elaine K., Gorden, Phillip, O'Rahilly, Stephen, and Savage, David B.

Subjects
Control, Genetic aspects, Research, Risk factors, Causes of, Health aspects, HDL cholesterol -- Health aspects -- Research -- Genetic aspects, Insulin resistance -- Causes of -- Genetic aspects -- Research -- Risk factors, Dyslipidemias -- Risk factors -- Control -- Research -- Genetic aspects, Cholesterol, HDL -- Health aspects -- Research -- Genetic aspects
Abstract

Introduction The burgeoning pandemic of obesity is a critical health care concern because of the vast associated burden of premature morbidity and mortality. This is predominantly due to accelerated atherosclerosis, [...], Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.

Published
2009

29. sj-pdf-1-jcb-10.1177_0271678X211042112 - Supplemental material for Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction

Author

Khellaf, Abdelhakim, Garcia, Nuria Marco, Tajsic, Tamara, Alam, Aftab, Stovell, Matthew G, Killen, Monica J, Howe, Duncan J, Guilfoyle, Mathew R, Jalloh, Ibrahim, Timofeev, Ivan, Murphy, Michael P, Carpenter, T Adrian, Menon, David K, Ercole, Ari, Hutchinson, Peter J, Carpenter, Keri LH, Thelin, Eric P, and Helmy, Adel

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211042112 for Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction by Abdelhakim Khellaf, Nuria Marco Garcia, Tamara Tajsic, Aftab Alam, Matthew G Stovell, Monica J Killen, Duncan J Howe, Mathew R Guilfoyle, Ibrahim Jalloh, Ivan Timofeev, Michael P Murphy, T Adrian Carpenter, David K Menon, Ari Ercole, Peter J Hutchinson, Keri LH Carpenter, Eric P Thelin and Adel Helmy in Journal of Cerebral Blood Flow & Metabolism

Published
2021
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31. GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition

Author

Murley, Alexander G, Rouse, Matthew A, Jones, P Simon, Ye, Rong, Hezemans, Frank H, O'Callaghan, Claire, Frangou, Polytimi, Kourtzi, Zoe, Rua, Catarina, Carpenter, T Adrian, Rodgers, Christopher T, Rowe, James B, Murley, Alexander [0000-0003-0813-0670], Rouse, Matthew [0000-0002-3157-4301], Jones, Simon [0000-0001-9695-0702], Ye, Rong [0000-0003-2529-7755], Frangou, Poly [0000-0003-3524-0306], Kourtzi, Zoe [0000-0001-9441-7832], Carpenter, Adrian [0000-0002-2939-8222], Rodgers, Christopher [0000-0003-1275-1197], Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository

Subjects
Aged, 80 and over, Male, Neurotransmitter Agents, Magnetic Resonance Spectroscopy, impulsivity, glutamate, progressive supranuclear palsy, Middle Aged, Neuropsychological Tests, frontotemporal dementia, Magnetic Resonance Imaging, GABA, Inhibition, Psychological, Glutamates, mental disorders, Reaction Time, Humans, Female, Supranuclear Palsy, Progressive, Frontotemporal Lobar Degeneration, gamma-Aminobutyric Acid, Aged, Visual Cortex
Abstract

Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson's syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

Published
2020

33. Short term arterial remodelling in the aortae of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging — implications for human pathology

Author

Hegyi, Laszlo, Hockings, Paul D., Benson, G. Martin, Busza, Albert L., Overend, Philip, Grimsditch, David C., Burton, Katherine J., Lloyd, Heather, Whelan, Greg A., Skepper, Jeremy N., Vidgeon-Hart, Martin P., Carpenter, T. Adrian, Reid, David G., Suckling, Keith E., and Weissberg, Peter L.

Published
2004
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37. Concordant biology underlies discordant imaging findings: diffusivity behaves differently in grey and white matter post acute neurotrauma

Author

Newcombe, Virginia F. J., primary, Williams, Guy B., additional, Nortje, Jurgens, additional, Bradley, Peter G., additional, Chatfield, Doris A., additional, Outtrim, Joanne G., additional, Harding, Sally G., additional, Coles, Jonathan P., additional, Maiya, Bala, additional, Gillard, Jonathan H., additional, Hutchinson, Peter J., additional, Pickard, John D., additional, Carpenter, T. Adrian, additional, and Menon, David K., additional

Published
2008
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38. Predicting Infarction Within the Diffusion-Weighted Imaging Lesion: Does the Mean Transit Time Have Added Value?

Author

Carrera, Emmanuel, Jones, P. Simon, Alawneh, Josef A., Klærke Mikkelsen, Irene, Cho, Tae-Hee, Siemonsen, Suzanne, Guadagno, Joseph V., Mouridsen, Kim, Ribe, Lars, Hjort, Niels, Fryer, Tim D., Carpenter, T. Adrian, Aigbirhio, Franklin I., Fiehler, Jens, Nighoghossian, Norbert, Warburton, Elizabeth A., Ostergaard, Leif, and Baron, Jean-Claude

Published
2011
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39. GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition

Author

Murley, Alexander G, primary, Rouse, Matthew A, additional, Jones, P Simon, additional, Ye, Rong, additional, Hezemans, Frank H, additional, O’Callaghan, Claire, additional, Frangou, Polytimi, additional, Kourtzi, Zoe, additional, Rua, Catarina, additional, Carpenter, T Adrian, additional, Rodgers, Christopher T, additional, and Rowe, James B, additional

Published
2020
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46. Diffusion in aqueous gels. Mutual diffusion coefficients measured by one-dimensional nuclear magnetic resonance imaging

Author

Balcom, Bruce J., Fischer, Alan E., Carpenter, T. Adrian, and Hall, Laurance D.

Subjects
Nuclear magnetic resonance spectroscopy -- Methods, Silica gel -- Research, Magnetism -- Research, Chemistry
Abstract

One-dimensional nuclear magnetic resonance imaging effectively and rapidly determined the mutual diffusion coefficients of paramagnetic compounds. The general principle behind this method concerned the relationship between spin-lattice relaxation rates and paramagnetic molecule concentration. Moreover, the concentration approaching the leading edge of the diffusion front could be easily monitored at relatively short distances. Sample experiments involving 4-amino-TEMPO and copper sulfate paramagnetic reagents in 105 polyacrylamide, 1% agarose and silica gel media were presented.

Published
1993

48. Further evidence for a non-cortical origin of mirror movements after stroke

Author

Calautti, Cinzia, Jones, P Simon, Naccarato, Marcello, Sharma, Nikhil, Carpenter, T Adrian, Warburton, Elisabeth A, Baron, Jean-Claude, Jones, Simon [0000-0001-9695-0702], Carpenter, Adrian [0000-0002-2939-8222], Baron, Jean-Claude [0000-0002-5264-2588], and Apollo - University of Cambridge Repository

Subjects
Stroke, Movement Disorders, Humans, Longitudinal Studies
Abstract

Ejaz et al. (2018) are to be commended for showing no evidence for a cortical origin of post-stroke mirror movements. Using functional MRI during affected-finger presses in recovering adult-onset stroke patients, they found no consistent relationship between contralesional sensorimotor cortex (cSM1) activation and quantitative indices of mirror movements; specifically, mirror movements were not linked to the presence of cSM1 overactivation, arguing against the classic ‘transcallosal’ mechanism heretofore widely believed to cause mirror movements (Di Pino et al., 2014). We wish to report findings—previously published in abstract form (Calautti, 2008)—that further support the idea that mirror movements are not cortically mediated. We also present data that confirm that mirror movements can involve the affected (i.e. paretic) hand during movement of the unaffected (i.e. non-paretic) hand, also arguing in favour of disruption of a bilaterally-organized system.

Published
2019

49. A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain

Author

Jalloh, Ibrahim, Helmy, Adel, Howe, Duncan J, Shannon, Richard J, Grice, Peter, Mason, Andrew, Gallagher, Clare N, Murphy, Michael P, Pickard, John D, Menon, David K, Carpenter, T Adrian, Hutchinson, Peter J, Carpenter, Keri LH, Helmy, Adel [0000-0002-0531-0556], Grice, Peter [0000-0003-4658-4534], Murphy, Mike [0000-0003-1115-9618], Pickard, John [0000-0002-5762-6667], Menon, David [0000-0002-3228-9692], Carpenter, Adrian [0000-0002-2939-8222], Hutchinson, Peter [0000-0002-2796-1835], Carpenter, Keri [0000-0001-8236-7727], and Apollo - University of Cambridge Repository

Subjects
Adult, Brain Chemistry, Male, Magnetic Resonance Spectroscopy, Adolescent, microdialysis, Glutamine, education, Citric Acid Cycle, Original Articles, traumatic brain injury (human), Middle Aged, NMR, nervous system diseases, Young Adult, nervous system, 3-13C lactate, brain metabolism, Brain Injuries, Traumatic, Humans, Female, Lactic Acid, Dialysis, Oxidation-Reduction
Abstract

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with “normal” control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0–11.1) % in TBI and 5.7 (4.6–6.8) % in control brain, for C3 0 (0–5.0) % in TBI and 0 (0–0) % in control brain, and for C2 2.9 (0–5.7) % in TBI and 1.8 (0–3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI “emergency option.”

Published
2018
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