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Glucagon-like pepti...
Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats
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- Darsalia, Vladimer (författare)
- Karolinska Institutet,Karolinska institutet
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- Mansouri, Shiva (författare)
- Karolinska Institutet,Karolinska institutet
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- Ortsater, Henrik (författare)
- Karolinska Institutet,Karolinska institutet
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- Olverling, Anna (författare)
- Karolinska Institutet,Karolinska institutet
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- Nozadze, Nino (författare)
- Karolinska Institutet,Karolinska institutet
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- Kappe, Camilla (författare)
- Karolinska Institutet,Karolinska institutet
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- Iverfeldt, Kerstin (författare)
- Stockholms universitet,Institutionen för neurokemi,Stockholms universitet, Institutionen för neurokemi
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- Tracy, Linda M. (författare)
- Stockholms universitet,Institutionen för neurokemi,Stockholms universitet, Institutionen för neurokemi
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- Grankvist, Nina (författare)
- Karolinska institutet
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- Sjöholm, Åke (författare)
- Karolinska Institutet,Karolinska institutet
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- Patrone, Cesare (författare)
- Karolinska Institutet,Karolinska institutet
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(creator_code:org_t)
- Portland Press, 2012
- 2012
- Engelska.
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Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 122:9-10, s. 473-483
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Diabetes is a strong risk factor for premature and severe stroke. The GLP-IR (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto-Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 mu g/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2-4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-IR agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
Nyckelord
- exendin-4 (Ex-4)
- Goto-Kakizaki (GK) rat
- middle cerebral artery occlusion (MCAO)
- neurogenesis
- neuroprotection
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Darsalia, Vladim ...
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Mansouri, Shiva
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Ortsater, Henrik
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Olverling, Anna
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Nozadze, Nino
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Kappe, Camilla
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visa fler...
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Iverfeldt, Kerst ...
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Tracy, Linda M.
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Grankvist, Nina
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Sjöholm, Åke
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Patrone, Cesare
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visa färre...
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Clinical Science
- Av lärosätet
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Stockholms universitet
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Karolinska Institutet
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Högskolan i Gävle