The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery
Type 2 diabetes (T2D) impairs post-stroke recovery, and the underlying mechanisms are unknown. Insulin resistance (IR), a T2D hallmark that is also closely linked to aging, has been associated with impaired post-stroke recovery. However, whether IR worsens stroke recovery is unknown. We addressed th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3989 |
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| author | Ellen Vercalsteren Dimitra Karampatsi Doortje Dekens Aikaterini Letsiou Alexander Zabala Mihaela Romanitan Thomas Klein Thomas Nyström Vladimer Darsalia Cesare Patrone |
| author_facet | Ellen Vercalsteren Dimitra Karampatsi Doortje Dekens Aikaterini Letsiou Alexander Zabala Mihaela Romanitan Thomas Klein Thomas Nyström Vladimer Darsalia Cesare Patrone |
| author_sort | Ellen Vercalsteren |
| collection | DOAJ |
| description | Type 2 diabetes (T2D) impairs post-stroke recovery, and the underlying mechanisms are unknown. Insulin resistance (IR), a T2D hallmark that is also closely linked to aging, has been associated with impaired post-stroke recovery. However, whether IR worsens stroke recovery is unknown. We addressed this question in mouse models where early IR, with or without hyperglycemia, was induced by chronic high-fat diet feeding or sucrose supplementation in the drinking water, respectively. Furthermore, we used 10-month-old mice, spontaneously developing IR but not hyperglycemia, where IR was normalized pharmacologically pre-stroke with Rosiglitazone. Stroke was induced by transient middle cerebral artery occlusion and recovery was assessed by sensorimotor tests. Neuronal survival, neuroinflammation and the density of striatal cholinergic interneurons were also assessed by immunohistochemistry/quantitative microscopy. Pre-stroke induction and normalization of IR, respectively, worsened and improved post-stroke neurological recovery. Moreover, our data indicate a potential association of this impaired recovery with exacerbated neuroinflammation and a decreased density of striatal cholinergic interneurons. The global diabetes epidemic and population aging are dramatically increasing the percentage of people in need of post-stroke treatment/care. Our results suggest that future clinical studies should target pre-stroke IR to reduce stroke sequelae in both diabetics and elderly people with prediabetes. |
| first_indexed | 2024-03-11T08:40:38Z |
| format | Article |
| id | doaj.art-335aef4f2a114838b7b70182efa2d937 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:40:38Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-335aef4f2a114838b7b70182efa2d9372023-11-16T21:07:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244398910.3390/ijms24043989The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional RecoveryEllen Vercalsteren0Dimitra Karampatsi1Doortje Dekens2Aikaterini Letsiou3Alexander Zabala4Mihaela Romanitan5Thomas Klein6Thomas Nyström7Vladimer Darsalia8Cesare Patrone9NeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeurology Department, Internal Medicine, Södersjukhuset, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenBoehringer Ingelheim Pharma GmbH & Co., KG, 88400 Biberach, GermanyNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenNeuroCardioMetabol Group, Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, 118 83 Stockholm, SwedenType 2 diabetes (T2D) impairs post-stroke recovery, and the underlying mechanisms are unknown. Insulin resistance (IR), a T2D hallmark that is also closely linked to aging, has been associated with impaired post-stroke recovery. However, whether IR worsens stroke recovery is unknown. We addressed this question in mouse models where early IR, with or without hyperglycemia, was induced by chronic high-fat diet feeding or sucrose supplementation in the drinking water, respectively. Furthermore, we used 10-month-old mice, spontaneously developing IR but not hyperglycemia, where IR was normalized pharmacologically pre-stroke with Rosiglitazone. Stroke was induced by transient middle cerebral artery occlusion and recovery was assessed by sensorimotor tests. Neuronal survival, neuroinflammation and the density of striatal cholinergic interneurons were also assessed by immunohistochemistry/quantitative microscopy. Pre-stroke induction and normalization of IR, respectively, worsened and improved post-stroke neurological recovery. Moreover, our data indicate a potential association of this impaired recovery with exacerbated neuroinflammation and a decreased density of striatal cholinergic interneurons. The global diabetes epidemic and population aging are dramatically increasing the percentage of people in need of post-stroke treatment/care. Our results suggest that future clinical studies should target pre-stroke IR to reduce stroke sequelae in both diabetics and elderly people with prediabetes.https://www.mdpi.com/1422-0067/24/4/3989type 2 diabetesstrokeinsulin resistanceneurological recoveryRosiglitazone |
| spellingShingle | Ellen Vercalsteren Dimitra Karampatsi Doortje Dekens Aikaterini Letsiou Alexander Zabala Mihaela Romanitan Thomas Klein Thomas Nyström Vladimer Darsalia Cesare Patrone The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery International Journal of Molecular Sciences type 2 diabetes stroke insulin resistance neurological recovery Rosiglitazone |
| title | The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery |
| title_full | The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery |
| title_fullStr | The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery |
| title_full_unstemmed | The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery |
| title_short | The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery |
| title_sort | pre stroke induction and normalization of insulin resistance respectively worsens and improves functional recovery |
| topic | type 2 diabetes stroke insulin resistance neurological recovery Rosiglitazone |
| url | https://www.mdpi.com/1422-0067/24/4/3989 |
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