{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:11:49Z","timestamp":1789863109840,"version":"4.0.1"},"reference-count":58,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":2737,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.5\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:p>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\u00a02 diabetic Goto\u2013Kakizaki rats were treated peripherally for 4\u00a0weeks with Ex-4 at 0.1, 1 or 5\u00a0\u03bcg\/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2\u20134\u00a0weeks 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.<\/jats:p>","DOI":"10.1042\/cs20110374","type":"journal-article","created":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T04:34:08Z","timestamp":1323318848000},"page":"473-483","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type\u00a02 diabetic rats"],"prefix":"10.1042","volume":"122","author":[{"given":"Vladimer","family":"Darsalia","sequence":"first","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Orts\u00e4ter","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Olverling","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Nozadze","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Kappe","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Iverfeldt","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Stockholm University, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda\u00a0M.","family":"Tracy","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Stockholm University, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Grankvist","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5ke","family":"Sj\u00f6holm","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Patrone","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,1,26]]},"reference":[{"key":"2021113010194554700_B1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1747-4949.2008.00187.x","article-title":"Risk factors for ischaemic stroke","volume":"3","author":"Allen","year":"2008","journal-title":"Int. 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