Abstract
BackgroundOver 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).MethodsHyperglycemia 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]).ResultsThe 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.ConclusionsOur 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.
Highlights
Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome
Mortality Sixteen rats were excluded from the study: 13 died after surgical induction of permanent middle cerebral artery occlusion and three were excluded because they did not show lesions on magnetic resonance imaging (MRI) analysis
It can be inferred that hAD-MSC treatment induces recovery which is not related to changes in blood glucose levels
Summary
Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Various studies have demonstrated that more than 50% of acute stroke patients. Gómez-de Frutos et al Stem Cell Research & Therapy (2019) 10:212 present hyperglycemia on admission which predicts higher mortality and morbidity [7,8,9]. Hyperglycemia in acute stroke is associated with a poor outcome, exacerbating processes involved in ischemic brain injury [10, 11]. The effects of comorbidities including hyperglycemia on therapeutic effects are poorly studied [12], this aspect is emphasized in The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) recommendations [13, 14]
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