Early cerebral hemodynamic, metabolic, and histological changes in hypoxic–ischemic fetal lambs during postnatal life

Rey-Santano Rey-Santano

doi:10.3389/fnins.2011.00111

Abstract

The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic–ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

Highlights

Perinatal asphyxia is produced by a reduction in blood flow or oxygenation and most likely for both reasons (Vannucci, 1990; Johnston et al, 2001)
This study aims to: (1) assess changes in total and regional cerebral blood flow (RCBF); (2) describe changes in cerebral brain metabolism; (3) analyze the activity of antioxidant enzymes; and (4) evaluate histological changes in the brain during the first 3 h of postnatal life following induction of severe fetal asphyxia
The transition from fetal to neonatal life is a time of rapid physiological changes that may be aggravated if episodes of asphyxia occur during fetal life

Summary

Introduction

Perinatal asphyxia is produced by a reduction in blood flow (ischemia) or oxygenation (hypoxia) and most likely for both reasons (Vannucci, 1990; Johnston et al, 2001). Many experimental models have been used to study hemodynamic and neurological changes in preterm or near-term fetal lambs in which an HI event is produced by means of internal iliac artery occlusion, reduction of maternal inspired O2, or umbilical cord occlusion (Gunn et al, 1992; Penning et al, 1994; Ikeda et al, 1998a). These studies did not, investigate postnatal resuscitation treatments and evaluation of brain damage during the neonatal period (postpartum) as fetuses continued to be on placental respiration. Other than those to assess resuscitation techniques focused on immature lungs, no studies seem to have been published on brain damage during preterm life

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