The NeuroCardioMetabol Group

Our research focus is on the pathophysiological mechanisms at the basis of the complications of diabetes and obesity, with main emphasis on stroke. We also work on the identification of both life-style and pharmacological strategies to improve neurological recovery after stroke.

Our group was the first to show that drugs targeting the glucagon-like peptide receptor 1 (GLP-1R) and inhibiting the enzyme DPP-4 are neuroprotective and can improve recovery after stroke in animal models of diabetes and obesity. Moreover, we recently found out that weight loss strategies achieved before stroke strongly enhance neurological recovery.

Our research is translational as we use preclinical experimental models and perform clinical research with randomized clinical studies and epidemiological methods. Recently we showed the detrimental role of insulin resistance and hyperglycemia to increase stroke risk using Sweden's National Diabetes Registers.

The NeuroCardioMetabol Group
The NeuroCardioMetabol Group

Research group leaders

Thomas Nyström

Professor, joint leadership of the group

Cesare Patrone

Associate Professor, joint leadership of the group

Group members

Vladimer Darsalia

Senior Scientist and Docent, responsible of the preclinical in vivo activities

Martin Larsson

MD, PhD, Post doc

Grazyna Lietzau

Post doc, preclinical

Ellen Vercalsteren

PhD, Post doc

Alexander Zabala

MD, PhD student

Dimitra Karampatsi

MSc, PhD student

Buster Mannheimer

MD, PhD, Associate professor

Cecilia Bergh Fahlén

PhD Student

Collaborations

The group has ongoing partnerships with Professors Claes-Göran Östensson, Henrik Druid, Tomas Hökfelt, Helena Erlandsson Harris (KI); with Associate Professors Sergiu-Bogdan Catrina , André Fisahn, Jan Kehr, Camilla Krizhanovskii, Martin Holzman, Ulrik Sartipy, Anna-Norhammar (KI); with Professor Jan Eriksson (Uppsala University); with Professors Milos Pekny and Carina Mallard and with Dr. Maria E Johansson (University of Gothenburg); with Professors Gesine Paul and Joao Duarte (Lund University); with Dr. Stefania Ceruti and Giulia Magni (University of Milan), Professor Massimo Collino (Turin University) and with Professor Mariagrazia Grilli (Novara University). We also have an ongoing collaboration with Boehringer Ingelheim Pharma GmbH & Co. KG, Germany, since 2011.

Projects

We were the first to demonstrate (Nyström et al AJP 2004) that the incretin hormone glucagon-like peptide 1 (GLP-1) improves endothelial function in type 2 diabetic (T2D) patients. We were also the first group to show the acute neuroprotection mediated by incretin mimetics and of dipeptidyl peptidase-4 inhibitors in animal models of T2D (Darsalia et al, Cli Sci 2012; Darsalia et al 2013 Diabetes), as well as effects of these drugs to also enhance post-stroke neurological recovery (Augestad et al, 2021, Diabetes; Augestad et al, 2022, British Journal of Pharmacology)

In a recent publication we showed that a diet change leading to weight loss before stroke enhances neurological recovery providing the first experimental evidence of life-style strategies based on weight loss to decrease long-term sequelae in diabetes and obesity (Karampatsi et al, 2022, Cardiovascular Diabetology).

We also showed that T1D patients have a dire prognosis after coronary artery bypass grafting (CABG) than non-diabetics (Holzmann et al JACC 2015) and that glycemic control is a key predictor for mortality in T1D after CABG (Nyström et al JACC 2015) as for T2D (Kuhl et al Int J Cardiol 2015). Moreover we are participating in population based studies evaluating prevalence, incidence and life expectancy of pharmacologically treated T2D patients (Norhammar et al, Diabetologia 2016) and effects of novel oral glucose lowering drugs (Nyström et al, Diabetes obesity and metabolism, 2017).

Preclinically, we showed that the anti-stroke efficacy by DPP-4 inhibitors is not mediated via GLP-1 (Darsalia et al Diabetes Obes Metab 2016) but SDF1a (Chiazza et al. Cardiovasc Diabetol 2017). We also provided new insights on how T2D impairs neuroplasticity and neurogenesis during aging (Lietzau et al Psychoneuroendocrinol. 2017 and Acta Neuropathol Commun 2018, Mansouri et al PLOS One 2016, Hussain S et al J Alzheimers Dis. 2014); observations that could be at the basis of decreased olfaction and cognitive decline in T2D.

Research support

  1. The Swedish Brain Foundation and the FANG foundation; 2021-2022 (Patrone)
  2. STROKE Riksförbundet; 2018-2020 (Darsalia)
  3. Ulla Hamberg Angeby och Lennart Angebys Stiftelse, 2020 (Darsalia)
  4. Diabetesfonden; 2020-2021 (Patrone)
  5. The Swedish Heart-Lung Foundation; 2020-2022 (Nyström)
  6. Svensk Förening för Diabetologi; 2019 (Lietzau))
  7. The Swedish Research Council (Vetenskasprådet); 2018-2021 (Patrone)
  8. The Swedish Heart-Lung Foundation; 2016-2019 (Nyström)
  9. European Foundation for the Study of Diabetes (EFSD)/Sanofi European Diabetes Research Programme in Macrovascular Complications; 2019 (Patrone)
  10. Diabetesfonden; 2017 (Nyström).
  11. Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; 2012-2017 (Patrone)
  12. NovoNordisk foundation; 2018 (Nyström)
  13. EFSD Albert Renold Travel Fellowship Programme to Dr Fausto Chiazza; 2018
  14. Karolinska Institutet (Foundation for Geriatric Diseases); 2019 (Pintana)
  15. KI Stiftelser och Fonder; 2019 (Lietzau)
  16. Åhlén Stiftelse; 2012-2018 (Patrone)
  17. Stiftelsen för Gamla Tjänarinnor; 2019 (Lietzau)
  18. O. E. och Edla Johanssons Stiftelse; 2016-2018 (Patrone)
  19. Magnus Bergvalls Stiftelse; 2016 (Patrone)
  20. STROKE Riksförbundet; 2018-2020 (Patrone)
  21. Stiftelsen för Gamla Tjänarinnor; 2017 (Darsalia)
  22. Syskonen Svensson Stiftelse; 2017 (Patrone)
  23. ALF; 2016-2020 (Nyström)
  24. EFSD; 2011 (Darsalia)
  25. EFSD; 2009 and 2013 (Patrone)
  26. Diabetes Wellness; 2010 (Patrone)

Articles

Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke.
Karampatsi D, Zabala A, Wilhelmsson U, Dekens D, Vercalsteren E, Larsson M, Nyström T, Pekny M, Patrone C, Darsalia V
Cardiovasc Diabetol 2021 12;20(1):240

Normalisation of glucose metabolism by exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice.
Augestad IL, Dekens D, Karampatsi D, Elabi O, Zabala A, Pintana H, Larsson M, Nyström T, Paul G, Darsalia V, Patrone C
Br J Pharmacol 2021 May;():

Regulation of Glycemia in the Recovery Phase After Stroke Counteracts the Detrimental Effect of Obesity-Induced Type 2 Diabetes on Neurological Recovery.
Augestad IL, Pintana H, Larsson M, Krizhanovskii C, Nyström T, Klein T, Darsalia V, Patrone C
Diabetes 2020 09;69(9):1961-1973

Dipeptidyl peptidase-4 inhibitors and sulfonylureas prevent the progressive impairment of the nigrostriatal dopaminergic system induced by diabetes during aging.
Lietzau G, Magni G, Yoshitake T, Candeias E, Nyström T, Darsalia V, Patrone C, et al
Neurobiol. Aging 2020 May;89():12-23

Glycemic Control in Type 1 Diabetes and Long-Term Risk of Cardiovascular Events or Death After Coronary Artery Bypass Grafting.
Nyström T, Holzmann MJ, Eliasson B, Kuhl J, Sartipy U
J. Am. Coll. Cardiol. 2015 Aug;66(5):535-43

Glycemic Control in Type 1 Diabetes and Long-Term Risk of Cardiovascular Events or Death After Coronary Artery Bypass Grafting.
Nyström T, Holzmann MJ, Eliasson B, Kuhl J, Sartipy U
J. Am. Coll. Cardiol. 2015 Aug;66(5):535-43

Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease.
Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, et al
Am. J. Physiol. Endocrinol. Metab. 2004 Dec;287(6):E1209-15

Type 2 diabetes impairs odour detection, olfactory memory and olfactory neuroplasticity; effects partly reversed by the DPP-4 inhibitor Linagliptin.
Lietzau G, Davidsson W, Östenson CG, Chiazza F, Nathanson D, Pintana H, et al
Acta Neuropathol Commun 2018 02;6(1):14

Gliptin-mediated neuroprotection against stroke requires chronic pretreatment and is independent of glucagon-like peptide-1 receptor.
Darsalia V, Larsson M, Lietzau G, Nathanson D, Nyström T, Klein T, et al
Diabetes Obes Metab 2016 May;18(5):537-41

The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride.
Darsalia V, Ortsäter H, Olverling A, Darlöf E, Wolbert P, Nyström T, et al
Diabetes 2013 Apr;62(4):1289-96

Collaboration in Science 2022, October 6-7th

Diet-induced weight loss in obese/diabetic mice normalizes glucose metabolism and promotes functional recovery after stroke.

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