DB20-0095_Augestad_et_al_OnlineAppendix_Clean_version.docx (531.08 kB)

The regulation of glycemia in the recovery phase after stroke counteracts the detrimental effect of obesity-induced type 2 diabetes on neurological recovery

Download (531.08 kB)
figure
posted on 15.06.2020 by Ada Admin, Ingrid Lovise Augestad, Hiranya Pintana, Martin Larsson, Camilla Krizhanovskii, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
The interplay between obesity and T2D in post-stroke 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 post-stroke 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 (PV)+ interneurons were quantified by immunohistochemistry.

T2D/obesity impaired post-stroke neurological recovery in association with hyperglycemia, neuroinflammation and atrophy of PV+ interneurons. Both drugs counteracted these effects. In non-diabetic 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 based on efficacious glycemia regulation, even if initiated days after stroke.

Funding

Financial support was provided by the Swedish Research Council, the European Foundation for the Study of Diabetes (EFSD)/Sanofi European Diabetes Research Programme in Macrovascular Complications, the Swedish Heart-Lung Foundation, Diabetesfonden, Svensk Förening för Diabetologi, Karolinska Institutet (Foundation for Geriatric Diseases and KI Stiftelser och Fonder), Stohnes Stiftelse, O. E. och Edla Johanssons Stiftelse, Magnus Bergvalls Stiftelse, STROKE Riksförbundet, Gamla Tjänarinnor Stiftelse and by the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet.

History

Exports

Logo branding

Exports