Experimental modeling of hypoxia in pregnancy and early postnatal life

Abstract

The important role of equilibrium of environmental factors during the embryo-fetal period is undisputable. Women of reproductive age are increasingly exposed to various environmental risk factors such as hypoxia, prenatal viral infections, use of drugs, smoking, complications of birth or stressful life events. These early hazards represent an important risk for structural and/or functional maldevelopment of the fetus and neonates. Impairment of oxygen/energy supply during the pre- and perinatal period may affect neuronal functions and induce cell death. Thus when death of the newborn is not occurring following intrauterine hypoxia, various neurological deficits, including hyperactivity, learning disabilities, mental retardation, epilepsy, cerebral palsy, dystonia etc., may develop both in humans and in experimental animals. In our animal studies we used several approaches for modeling hypoxia in rats during pregnancy and shortly after delivery, i.e. chronic intrauterine hypoxia induced by the antiepileptic drug phenytoin, neonatal anoxia by decreased oxygen saturation in 2-day-old pups. Using these models we were able to test potential protective properties of natural (vitamin E, melatonin) and synthetic (stobadine) compounds. Based on our results, stobadine was also able to reduce hypoxia-induced hyperactivity and the antioxidant capacity of stobadine exceeded that of vitamin E and melatonin, and contrary to vitamin E, stobadine had no adverse effects on developing fetus and offspring.

The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups

“…It cannot be excluded that such mechanism might be responsible for lactate upregulation found in the brain of isoflurane-treated juvenile and adult mice (Boretius et al ., 2013 ). However, neonatal rats are known to be wellresistant to hypoxic conditions up to PD4–5 (Mach et al ., 2009 ) and the observed reduction in the breath rate of our isoflurane-treated pups did not affect lactate levels in their hippocampus, as shown by MRS quantification ( Figure 2c ).…”

Modern Methods of Perinatal Hypoxic-Ischemic Brain Injury Modeling in Vivo

“…Выживших животных возвращают к кормящей самке. Использование указан-ной модели позволило провести исследование роли таких белков-мишеней, как PARP-1, XRCC1, ДНК-лигаза III␣, ДНК-полимераза ␤, ERCC2, ДНК-зависимая протеинки-наза, а также антиоксидантов и витаминов для терапии гипоксической энцефалопатии [35][36][37]. Установлена роль аноксии в развитии синдрома гиперактивности, созрева-нии нервной ткани, влиянии на пространственную память [38].…”

Neurobehavioral manifestations of developmental impairment of the brain

“…Prenatal and/or perinatal hypoxia-ischemia is a major factor for the development of cognitive dysfunctions in later life (Gitto et al ., 2009 ; Brucknerová et al ., 2008 ; Mach et al ., 2009 ). Memory and learning deficits are very frequent consequences of lack of oxygen and nutrition during brain development.…”