Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity
It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this g...
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Elsevier
2025-06-01
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| Series: | IBRO Neuroscience Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242124001106 |
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| author | Julien Clain David Couret Matthieu Bringart Olivier Meilhac Christian Lefebvre d’Hellencourt Nicolas Diotel |
| author_facet | Julien Clain David Couret Matthieu Bringart Olivier Meilhac Christian Lefebvre d’Hellencourt Nicolas Diotel |
| author_sort | Julien Clain |
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| description | It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring. In the present study, by performing a 30-minute middle cerebral artery occlusion (MCAO) on db/db (obese diabetics mice) and db/+ (controls) mice, we demonstrated that obese and diabetic mice displayed larger lesions (i.e. increased infarct volume, ischemic core, apoptotic cell number) and worsened neurological outcomes compared to their control littermates. We then investigated the formation of the glial scar in control and db/db mice 7 days post-stroke. Our observations argue in favor of a stronger and more persistent activation of astrocytes and microglia in db/db mice. Furthermore, an increased deposition of extracellular matrix (ECM) was observed in db/db vs control mice (i.e. chondroitin sulfate proteoglycan and collagen type IV). Consequently, we demonstrated for the first time that the db/db status is associated with increased astrocytic and microglial activation 7 days after stroke and resulted in higher deposition of ECM within the damaged area. Interestingly, the injury-induced neurogenesis appeared stronger in db/db as shown by the labeling of migrating neuroblast. This increase appeared correlated to the larger size of lesion. It nevertheless raises the question of the functional integration of the new neurons in db/db mice given the observed dense ECM, known to be repulsive for neuronal migration. Carefully limiting glial scar formation after stroke represents a promising area of research for reducing neuronal loss and limiting disability in diabetic/obese patients. |
| format | Article |
| id | doaj-art-2d52c59065e6418b975b8b3fb02de752 |
| institution | DOAJ |
| issn | 2667-2421 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj-art-2d52c59065e6418b975b8b3fb02de7522025-08-20T02:39:37ZengElsevierIBRO Neuroscience Reports2667-24212025-06-0118163010.1016/j.ibneur.2024.12.002Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesityJulien Clain0David Couret1Matthieu Bringart2Olivier Meilhac3Christian Lefebvre d’Hellencourt4Nicolas Diotel5Université de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, FranceUniversité de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, France; CHU de La Réunion, Saint-Pierre 97410, FranceUniversité de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, FranceUniversité de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, France; CHU de La Réunion, Saint-Pierre 97410, FranceUniversité de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, France; Correspondence to: Laboratory DéTROI - Inserm U1188 - Université de La Réunion - Campus Santé, Diabète athérothrombose Thérapies Réunion Océan Indien 77 Avenue du Docteur Jean-Marie Dambreville, Saint-Pierre, Réunion 97410, France.Université de la Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Pierre 97410, France; Correspondence to: Laboratory DéTROI - Inserm U1188 - Université de La Réunion - Campus Santé, Diabète athérothrombose Thérapies Réunion Océan Indien 77 Avenue du Docteur Jean-Marie Dambreville, Saint-Pierre, Réunion 97410, France.It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring. In the present study, by performing a 30-minute middle cerebral artery occlusion (MCAO) on db/db (obese diabetics mice) and db/+ (controls) mice, we demonstrated that obese and diabetic mice displayed larger lesions (i.e. increased infarct volume, ischemic core, apoptotic cell number) and worsened neurological outcomes compared to their control littermates. We then investigated the formation of the glial scar in control and db/db mice 7 days post-stroke. Our observations argue in favor of a stronger and more persistent activation of astrocytes and microglia in db/db mice. Furthermore, an increased deposition of extracellular matrix (ECM) was observed in db/db vs control mice (i.e. chondroitin sulfate proteoglycan and collagen type IV). Consequently, we demonstrated for the first time that the db/db status is associated with increased astrocytic and microglial activation 7 days after stroke and resulted in higher deposition of ECM within the damaged area. Interestingly, the injury-induced neurogenesis appeared stronger in db/db as shown by the labeling of migrating neuroblast. This increase appeared correlated to the larger size of lesion. It nevertheless raises the question of the functional integration of the new neurons in db/db mice given the observed dense ECM, known to be repulsive for neuronal migration. Carefully limiting glial scar formation after stroke represents a promising area of research for reducing neuronal loss and limiting disability in diabetic/obese patients.http://www.sciencedirect.com/science/article/pii/S2667242124001106astrogliosisCSPGMCAOdb/db miceextracellular matrixglial scar |
| spellingShingle | Julien Clain David Couret Matthieu Bringart Olivier Meilhac Christian Lefebvre d’Hellencourt Nicolas Diotel Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity IBRO Neuroscience Reports astrogliosis CSPG MCAO db/db mice extracellular matrix glial scar |
| title | Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| title_full | Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| title_fullStr | Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| title_full_unstemmed | Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| title_short | Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| title_sort | effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity |
| topic | astrogliosis CSPG MCAO db/db mice extracellular matrix glial scar |
| url | http://www.sciencedirect.com/science/article/pii/S2667242124001106 |
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