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- Title
Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats.
- Authors
Gómez-de Frutos, Mari Carmen; Laso-García, Fernando; Diekhorst, Luke; Otero-Ortega, Laura; Fuentes, Blanca; Jolkkonen, Jukka; Detante, Olivier; Moisan, Anaick; Martínez-Arroyo, Arturo; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María
- Abstract
Background: Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Our aim was to investigate the impact of hyperglycemia on behavioral recovery and brain repair of delivered human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) in a rat model of permanent middle cerebral artery occlusion (pMCAO). Methods: Hyperglycemia was induced in rats by the administration of nicotinamide and streptozotocin. The rats were then subjected to stroke by a pMCAO model. At 48 h post-stroke, 1 × 106 hAD-MSCs or saline were intravenously administered. We evaluated behavioral outcome, infarct size by MRI, and brain plasticity markers by immunohistochemistry (glial fibrillary acidic protein [GFAP], Iba-1, synaptophysin, doublecortin, CD-31, collagen-IV, and α-smooth muscle actin [α-SMA]). Results: The hyperglycemic group exhibited more severe neurological deficits; lesion size and diffusion coefficient were larger compared with the non-hyperglycemic rats. GFAP, Iba-1, and α-SMA were increased in the hyperglycemic group. The hyperglycemic rats administered hAD-MSCs at 48 h after pMCAO had improved neurological impairment. Although T2-MRI did not show differences in lesion size between groups, the rADC values were lower in the treated group. Finally, the levels of GFAP, Iba-1, and arterial wall thickness were lower in the treated hyperglycemic group than in the nontreated hyperglycemic group at 6 weeks post-stroke. Conclusions: Our data suggest that rats with hyperglycemic ischemic stroke exhibit increased lesion size and impaired brain repair processes, which lead to impairments in behavioral recovery after pMCAO. More importantly, hAD-MSC administration induced better anatomical tissue preservation, associated with a good behavioral outcome.
- Subjects
MESENCHYMAL stem cells; NEURAL stem cells; ADIPOSE tissues; GLIAL fibrillary acidic protein; RATS
- Publication
Stem Cell Research & Therapy, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
1757-6512
- Publication type
Article
- DOI
10.1186/s13287-019-1322-x