Vladimer Darsalia

Vladimer Darsalia

Principal Researcher | Docent
Visiting address: Södersjukhuset, Sjukhusbacken 17, 11883 Stockholm
Postal address: S1 Klinisk forskning och utbildning, Södersjukhuset, S1 KI SÖS Forskning Internmedicin, 118 83 Stockholm
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About me

  • *Researcher, Docent of Neuroscience*
    *Researh Group:* https://ki.se/en/kisos/the-neurocardiometabol-group [1]
    *2014 - 2018: Assistent professor, *Karolinska Institutet, Stockholm, Sweden
    *2010 - 2014: Post-doctoral fellow, *Karolinska Institutet, Stockholm, Sweden
    *2008 - 2010: Post-doctoral fellow, *Lund University, Lund, Sweden
    *2007: Ph.D. in Neurobiology, *Lund University, Lund, Sweden
    *2021: Docent in Neuroscience, * Karolinska Institutet, Sweden
    *2007: Ph.D. in Neurobiology, * Lund University, Sweden
    *2001: Bachelor in Biology, *Tbilisi State University, Georgia
    [1] https://ki.se/en/kisos/the-neurocardiometabol-group

Research

  • *TYPE 2 DIABETES AND STROKE*
    Prevalence of type 2 diabetes and its complications is rapidly rising
    worldwide. One of the major complications of diabetes is cardiovascular
    disease that often leads to a stroke. Diabetes not only doubles the risk of
    stroke, but also significantly impairs post-stroke recovery, often leading to
    lasting disabilities.
    The main subject of my research is the identification of the
    pathophysiological mechanisms by which diabetes impairs stroke recovery and
    the development of treatment strategies based on lifestyle and
    pharmacological interventions. This research and development effort is
    conducted in close collaboration with academic, clinical and industrial
    partners and involves both clinical and preclinical settings.
    Our group is also actively investigating the role of diabetes in other
    neurological complications that are overrepresented in the diabetic
    population, such as Parkinson’s disease, cognitive decline and dementias.
    *RESEARCH HIGHLIGHTS*
    * In a nationwide cohort study [1], our group demonstrated the link between
    insulin resistance (IR) and increased stroke risk and mortality in type 2
    diabetes (T2D), highlighting the need of novel therapeutics beyond simple
    glycaemic control. In following studies, using experimental T2D, IR and
    stroke models we showed that the IR is detrimental for stroke recovery and
    reversing it pre-stroke by lifestyle [2] or pharmacological [3]
    interventions leads to improved functional recovery.
    * Type 2 diabetes significantly impairs functional recovery after stroke
    [4]. However, Chronic regulation of glycaemia by DPP-4inhibitors [5],
    GLP-1R agonists [6], Sulfonylureas [7] and SGLT-2 inhibitors in post-acute
    recovery phase after stroke improves functional recovery in T2D in
    association with increased neuroplasticity and vascular remodelling.
    * T2D leads to impairments in nigrostriatal dopaminergic system along ageing
    by reducing dopamine release in striatum, potential increasing the risk of
    neurological disorders associated with impaired movement, attention,
    reward and learning (complications that are common in T2D people). This
    effect is reversed by chronic treatment with DPP-4inhibitors and
    sulfonylureas [8], showing the additional benefit of these drugs over
    standard T2D care.
    * Chronic GLP-1R agonist [9] and DPP-4 inhibitor [10] treatment reduce
    stroke-induced injury in T2D. This was the first demonstration the
    superior potential of GLP-1R agonists and DPP-4 inhibitors over standard
    T2D care as the potential strategy to in addition of treating T2D, also
    benefit T2D patients in case of stroke.
    * Human foetal neural stem cells differentiate into neurons [11] after
    grafting in stroke-damaged brain. The survival of grafted stem cells is
    better if grafted shortly after stroke. However, their capacity to migrate
    and differentiate into neurons is still conserved when grafting is delayed
    [12], indicating the potential efficacy of stem cell therapy for stroke
    even in chronic phase after stroke.
    * Stroke-induced neurogenesis persists chronically [13], in recovery phase
    after a stroke. Newly generated neuroblasts maintained directed migration
    towards injury site by stromal cell-derived factor-1alpha and its receptor
    CXCR4. During ageing [14], the neurogenic capacity of the brain in
    response to stroke is maintained despite the general reduction of basal
    neurogenesis.
    *SELECTED PUBLICATIONS, LAST 5 YEARS *
    1) DPP-4 Inhibitor and Sulfonylurea Differentially Reverse Type 2
    Diabetes-Induced Blood-Brain Barrier Leakage and Normalize Capillary
    Pericyte Coverage. [15] Elabi OF, Karampatsi D, Vercalsteren E, Lietzau
    G, Nyström T, Klein T, *Darsalia V*, Patrone C, Paul G. Diabetes. 2023
    Mar 1;72(3):405-414. doi: 10.2337/db22-0674.PMID: 36448982
    2) Diet-induced weight loss in obese/diabetic mice normalizes glucose
    metabolism and promotes functional recovery after stroke. [16] Karampatsi
    D, Zabala A, Wilhelmsson U, Dekens D, Vercalsteren E, Larsson M, Nyström
    T, Pekny M, Patrone C, *Darsalia V. *Cardiovasc Diabetol. 2021 Dec
    22;20(1):240. doi: 10.1186/s12933-021-01426-z.PMID: 34937562
    3) Estimated glucose disposal rate and risk of stroke and mortality in type
    2 diabetes: a nationwide cohort study. [17] Zabala A, *Darsalia V*, Lind
    M, Svensson AM, Franzén S, Eliasson B, Patrone C, Jonsson M, Nyström
    T.Cardiovasc Diabetol. 2021 Oct 6;20(1):202. doi:
    10.1186/s12933-021-01394-4.PMID: 34615525
    4) Normalisation of glucose metabolism by exendin-4 in the chronic phase
    after stroke promotes functional recovery in male diabetic mice. [18]
    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.
    2022 Feb;179(4):677-694. doi: 10.1111/bph.15524. Epub 2021 Jun
    16.PMID: 33973246
    5) Dipeptidyl peptidase-4 inhibitors and sulfonylureas prevent the
    progressive impairment of the nigrostriatal dopaminergic system induced
    by diabetes during aging. [19] Lietzau G, Magni G, Kehr J, Yoshitake T,
    Candeias E, Duarte AI, Pettersson H, Skogsberg J, Abbracchio MP, Klein T,
    Nyström T, Ceruti S, *Darsalia V*, Patrone C.Neurobiol Aging. 2020
    May;89:12-23. doi: 10.1016/j.neurobiolaging.2020.01.004. Epub 2020 Feb
    4.PMID: 32143981
    6) Obesity-induced type 2 diabetes impairs neurological recovery after
    stroke in correlation with decreased neurogenesis and persistent atrophy
    of parvalbumin-positive interneurons. [20] Pintana H, Lietzau G, Augestad
    IL, Chiazza F, Nyström T, Patrone C, *Darsalia V. *Clin Sci (Lond).
    2019 Jul 1;133(13):1367-1386. doi: 10.1042/CS20190180. Print 2019 Jul
    15.PMID: 31235555
    7) The effect of DPP-4 inhibition to improve functional outcome after stroke
    is mediated by the SDF-1α/CXCR4 pathway. [21] Chiazza F, Tammen H,
    Pintana H, Lietzau G, Collino M, Nyström T, Klein T, *Darsalia V*,
    Patrone C.Cardiovasc Diabetol. 2018 May 19;17(1):60. doi:
    10.1186/s12933-018-0702-3.PMID: 29776406
    8) Type 2 diabetes impairs odour detection, olfactory memory and olfactory
    neuroplasticity; effects partly reversed by the DPP-4 inhibitor
    Linagliptin. [22] Lietzau G, Davidsson W, Östenson CG, Chiazza F,
    Nathanson D, Pintana H, Skogsberg J, Klein T, Nyström T, *Darsalia V*,
    Patrone C.Acta Neuropathol Commun. 2018 Feb 23;6(1):14. doi:
    10.1186/s40478-018-0517-1.PMID: 29471869
    [1] https://pubmed.ncbi.nlm.nih.gov/34615525/
    [2] https://pubmed.ncbi.nlm.nih.gov/34937562/
    [3] https://pubmed.ncbi.nlm.nih.gov/36835405/
    [4] https://pubmed.ncbi.nlm.nih.gov/31235555/
    [5] https://pubmed.ncbi.nlm.nih.gov/32540876/
    [6] https://pubmed.ncbi.nlm.nih.gov/33973246/
    [7] https://pubmed.ncbi.nlm.nih.gov/32540876/
    [8] https://pubmed.ncbi.nlm.nih.gov/32143981/
    [9] https://pubmed.ncbi.nlm.nih.gov/22150224/
    [10] https://pubmed.ncbi.nlm.nih.gov/23209191/
    [11] https://pubmed.ncbi.nlm.nih.gov/17686040/
    [12] https://pubmed.ncbi.nlm.nih.gov/20531461/
    [13] https://pubmed.ncbi.nlm.nih.gov/16210404/
    [14] https://pubmed.ncbi.nlm.nih.gov/16002766/
    [15] https://pubmed.ncbi.nlm.nih.gov/36448982/
    [16] https://pubmed.ncbi.nlm.nih.gov/34937562/
    [17] https://pubmed.ncbi.nlm.nih.gov/34615525/
    [18] https://pubmed.ncbi.nlm.nih.gov/33973246/
    [19] https://pubmed.ncbi.nlm.nih.gov/32143981/
    [20] https://pubmed.ncbi.nlm.nih.gov/31235555/
    [21] https://pubmed.ncbi.nlm.nih.gov/29776406/
    [22] https://pubmed.ncbi.nlm.nih.gov/29471869/

Teaching

  • *Project Coordinator and Examiner *for degree projects in medicine (30hp)
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2023 - 31 December 2025
    AimType 2 diabetic (T2D) and elderly people have severe/persistent post-stroke disabilities and the causal mechanisms are unknown. Insulin resistance (IR), which is a hallmark of T2D, also afflicts up to 50% of non-diabetic elderly people (prediabetic). IR has been associated to poor stroke outcome. However, if the pharmacological targeting of IR improves stroke recovery is unknown and will be addressed in this experimental project.Project organisation/time plan/methodsThe project’s duration is 3 years. Most of the activities will take place at the PI’s lab where validated IR (aging- and high sucrose-induced), and stroke (middle cerebral artery occlusion) mouse models plus lab facilities are in place. One post-doc and one PhD student will perform the experiments. Stroke and T2D expertise is provided by co-PIs Dr Vladimer Darsalia and Prof Thomas Nyström. The cellular studies are in collaboration with Profs Gesine Paul (Lund Univ) and Milos Pekny (Gothenburg Univ).Relevance/ImplementationT2D and aging impair stroke recovery. Since T2D is reaching epidemic dimensions, the elderly population continues to grow, and both conditions are strong stroke risk factors, this creates a social burden with rising medical need. Positive results of this project will be important to develop new therapies targeting IR, in the preventive perspective to limit stroke sequelae in two of the largest populations at stroke risk. This could have remarkable implications for an enormous group of people.
  • Swedish Heart-Lung Foundation
    1 January 2020 - 31 December 2022
  • Swedish Research Council
    1 January 2019 - 31 December 2021
  • Swedish Research Council
    1 January 2010 - 31 December 2012

Employments

  • Principal Researcher, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, 2018-

Degrees and Education

  • Docent, Karolinska Institutet, 2021

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