RESUMO
Ischemic postconditioning (IPost) could decrease ischemia-reperfusion (IR) injury. It has not yet reported whether IPost is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism. The aim of this study was to examine the effect of IPost on myocardial IR injury in hyperthyroid male rats. Hyperthyroidism was induced with administration of thyroxine in drinking water (12 mg/L) over a period of 21 days. After thoracotomy, the hearts of control and hyperthyroid rats were perfused in the Langendorff apparatus and subjected to 30 minutes global ischemia, followed by 120 minutes reperfusion; IPost, intermittent early reperfusion, was induced instantly following ischemia. In control rats, IPost significantly improved the left ventricular developed pressure (LVDP) and ±dp/dt during reperfusion (p<0.05); however it had no effect in hyperthyroid rats. In addition, hyperthyroidism significantly increased basal NOx (nitrate+nitrite) content in serum (125.5±5.4 µmol/L vs. 102.8±3.7 µmol/L; p< 0.05) and heart (34.9±4.1 µmol/L vs. 19.9±1.94 µmol/L; p<0.05). In hyperthyroid groups, heart NOx concentration significantly increased after IR and IPost, whereas in the control groups, heart NOx were significantly higher after IR and lower after IPost (p< 0.05). IPost reduced infarct size (p<0.05) only in control groups. In hyperthyroid group subjected to IPost, aminoguanidine, an inducible nitric oxide (NO) inhibitor, significantly reduced both the infarct size and heart NOx concentrations. In conclusion, unlike normal rats, IPost cycles following reperfusion does not provide cardioprotection against IR injury in hyperthyroid rats; an effect that may be due to NO overproduction because it is restored by iNOS inhibition.
RESUMO
BACKGROUND: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity. METHODS: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (BDNF), calmodulin-dependent protein kinase (CAMKII), N-methyl-D-aspartate receptors (NMDAR), and cAMP-response element-binding protein (CREB) by western blotting and reverse transcription-polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1ß levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1. RESULTS: Post-natal exercise improved spatial memory (p < 0.05) and glucose levels (p < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression (p < 0.05) in emerging adulthood for both training groups. CONCLUSION: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level.