Sökning: L773:0012 1797 OR L773:1939 327X
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Regulation of Glyce...
Regulation of Glycemia in the Recovery Phase After Stroke Counteracts the Detrimental Effect of Obesity-Induced Type 2 Diabetes on Neurological Recovery
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Augestad, IL (författare)
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Pintana, H (författare)
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- Larsson, M (författare)
- Karolinska Institutet
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- Krizhanovskii, C (författare)
- Karolinska Institutet
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- Nystrom, T (författare)
- Karolinska Institutet
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Klein, T (författare)
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- Darsalia, V (författare)
- Karolinska Institutet
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- Patrone, C (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-06-15
- 2020
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:9, s. 1961-1973
- Relaterad länk:
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https://diabetes.dia...
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http://kipublication...
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https://doi.org/10.2...
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Abstract
Ämnesord
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- The interplay between obesity and type 2 diabetes (T2D) in poststroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined. We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy of two clinically used T2D drugs: the dipeptidyl peptidase 4 inhibitor linagliptin and the sulfonylurea glimepiride. We induced transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (after 7 months of high-fat diet [HFD]) and age-matched controls. After stroke, we replaced HFD with standard diet for 8 weeks to mimic the poststroke clinical situation. Linagliptin or glimepiride were administered daily from 3 days after tMCAO for 8 weeks. We assessed neurological recovery weekly by upper-limb grip strength. Brain damage, neuroinflammation, stroke-induced neurogenesis, and atrophy of parvalbumin-positive (PV+) interneurons were quantified by immunohistochemistry. T2D/obesity impaired poststroke neurological recovery in association with hyperglycemia, neuroinflammation, and atrophy of PV+ interneurons. Both drugs counteracted these effects. In nondiabetic mice, only linagliptin accelerated recovery. These findings shed light on the interplay between obesity and T2D in stroke recovery. Moreover, they promote the use of rehabilitative strategies that are based on efficacious glycemia regulation, even if initiated days after stroke.
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Diabetes
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