Academic Journal
Glucagonlike peptide-1 receptor activation reduces ischaemic brain damage following stroke
| العنوان: | Glucagonlike peptide-1 receptor activation reduces ischaemic brain damage following stroke |
|---|---|
| المؤلفون: | Vladimer Darsalia, Shiva Mansouri, Henrik Ortsäter, Anna Olverling, Nino Nozadze, Camilla Kappe, Kerstin Iverfeldt, Linda M Tracy, Nina Grankvist, Åke Sjöholm, Cesare Patrone |
| المساهمون: | The Pennsylvania State University CiteSeerX Archives |
| المصدر: | http://www.clinsci.org/content/ppclinsci/122/10/473.full.pdf. |
| سنة النشر: | 2012 |
| المجموعة: | CiteSeerX |
| الوصف: | A B S T R A C T Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (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 μg/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-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1071.7468; http://www.clinsci.org/content/ppclinsci/122/10/473.full.pdf |
| الاتاحة: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1071.7468 http://www.clinsci.org/content/ppclinsci/122/10/473.full.pdf |
| Rights: | Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: | edsbas.80CED035 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |