{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:33:43Z","timestamp":1792020823649,"version":"4.4.0"},"reference-count":84,"publisher":"Portland Press Ltd.","issue":"13","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":80,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic\/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain\u2019s self-repair mechanisms \u2013 stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl\/6j mice were fed 12 months with high-fat diet (HFD) and subjected to transient middle cerebral artery occlusion (tMCAO). We evaluated neurological recovery by upper-limb grip strength at 1 and 6 weeks after tMCAO. Gray and white matter damage, stroke-induced neurogenesis, and survival and potential atrophy of PV-interneurons were quantitated by immunohistochemistry (IHC) at 2 and 6 weeks after tMCAO. Obesity\/T2D impaired neurological function without exacerbating brain damage. Moreover, obesity\/T2D diminished stroke-induced neural stem cell (NSC) proliferation and neuroblast formation in striatum and hippocampus at 2 weeks after tMCAO and abolished stroke-induced neurogenesis in hippocampus at 6 weeks. Finally, stroke resulted in the atrophy of surviving PV-interneurons 2 weeks after stroke in both non-diabetic and obese\/T2D mice. However, after 6 weeks, this effect selectively persisted in obese\/T2D mice. We show in a preclinical setting of clinical relevance that obesity\/T2D impairs neurological functions in the stroke recovery phase in correlation with reduced neurogenesis and persistent atrophy of PV-interneurons, suggesting impaired neuroplasticity. These findings shed light on the mechanisms behind impaired stroke recovery in T2D and could facilitate the development of new stroke rehabilitative strategies for obese\/T2D patients.<\/jats:p>","DOI":"10.1042\/cs20190180","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T22:14:35Z","timestamp":1561414475000},"page":"1367-1386","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons"],"prefix":"10.1042","volume":"133","author":[{"given":"Hiranya","family":"Pintana","sequence":"first","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazyna","family":"Lietzau","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid\u00a0Lovise","family":"Augestad","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Chiazza","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0470-4606","authenticated-orcid":false,"given":"Cesare","family":"Patrone","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimer","family":"Darsalia","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2021113012304603900_B1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/ageing\/afn282","article-title":"Human and economic burden of stroke","volume":"38","author":"Di Carlo","year":"2009","journal-title":"Age Ageing"},{"key":"2021113012304603900_B2","doi-asserted-by":"publisher","first-page":"S85","DOI":"10.1016\/j.wneu.2011.07.023","article-title":"Epidemiology and the global burden of stroke","volume":"76","author":"Mukherjee","year":"2011","journal-title":"World Neurosurgery"},{"key":"2021113012304603900_B3","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1212\/WNL.0000000000001618","article-title":"Stroke and the noncommunicable diseases: a global burden in need of global advocacy","volume":"84","author":"Berkowitz","year":"2015","journal-title":"Neurology"},{"key":"2021113012304603900_B4","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1161\/STROKEAHA.114.006538","article-title":"Changes in functional outcome over the first year after stroke: an observational study from the Swedish stroke register","volume":"46","author":"Ullberg","year":"2015","journal-title":"Stroke"},{"key":"2021113012304603900_B5","doi-asserted-by":"publisher","first-page":"e2282","DOI":"10.1097\/MD.0000000000002282","article-title":"Impact of diabetes on stroke risk and outcomes: two nationwide retrospective cohort studies","volume":"94","author":"Liao","year":"2015","journal-title":"Medicine"},{"key":"2021113012304603900_B6","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1161\/01.STR.25.10.1977","article-title":"Stroke in patients with diabetes. 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