RESUMEN
BACKGROUND: After perinatal asphyxia, the cerebellum presents more damage than previously suggested. OBJECTIVES: To explore if the antioxidant N-acetylcysteine amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a neonatal pig model. METHODS: Twenty-four newborn pigs in two intervention groups were exposed to 8% oxygen and hypercapnia, until base excess fell to -20 mmol/l or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they received either NACA (NACA group, n = 12) or saline (vehicle-treated group, n = 12). One sham-operated group (n = 5) served as a control and was not subjected to hypoxia. Observation time after the end of hypoxia was 9.5 hours. RESULTS: The intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle-treated pigs was significantly higher than that in sham controls (p = 0.03). Treatment with NACA was associated with a trend to decreased intranuclear proteolytic activity (p = 0.08), There were significantly less mutations in the mtDNA of the NACA group compared with the vehicle-treated group, 2.0 × 10-4 (±2.0 × 10-4) versus 4.8 × 10-5(±3.6 × 10-4, p < 0.05). CONCLUSION: We found a trend to lower proteolytic activity in the core of Purkinje cells and significantly reduced mutation rate of mtDNA in the NACA group, which may indicate a positive effect of NACA after neonatal hypoxia. Measuring the proteolytic activity in the nucleus of Purkinje cells could be used to assess the effect of different neuroprotective substances after perinatal asphyxia.
Asunto(s)
Acetilcisteína/análogos & derivados , Asfixia Neonatal/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Células de Purkinje/efectos de los fármacos , Acetilcisteína/administración & dosificación , Acetilcisteína/farmacología , Animales , Asfixia Neonatal/genética , ADN Mitocondrial/efectos de los fármacos , ADN Mitocondrial/genética , Modelos Animales de Enfermedad , Humanos , Recién Nacido , Tasa de Mutación , Fármacos Neuroprotectores/farmacología , Proteolisis , Células de Purkinje/citología , Células de Purkinje/metabolismo , PorcinosRESUMEN
AIM: Inflammation is a major factor in the pathophysiology of bronchopulmonary dysplasia (BPD), and it contributes to accelerated telomere shortening and cellular ageing. This study aimed to determine its effect on telomere length and lung function in school-aged children born preterm with BPD. METHODS: We examined 29 children with BPD, born preterm in Stockholm county 1998-99, along with 28 children with allergic asthma born at term matched for age and gender. At 10 years of age, we measured relative telomere length (RTL) in blood by quantitative polymerase chain reaction, lung function by spirometry and inflammation by fractional exhaled nitric oxide and blood cytokines. RESULTS: RTL was not different in preterm born with BPD compared to term born children with asthma. The gender effect was strong in both groups; girls had significantly longer median RTL than boys (1.8 versus 1.5, p < 0.01). Short RTL was associated with low forced expiratory flow, also after adjusting for gender, but was not affected by severity of BPD or ongoing inflammation. CONCLUSION: Telomere length was similar in 10-year-old children born preterm with a history of BPD and term born children with allergic asthma. However, impaired lung function and male gender were associated with short telomeres.