Original Research ARTICLE

Front. Neurosci., 20 September 2011 | http://dx.doi.org/10.3389/fnins.2011.00111

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

Carmen Rey-Santano1*, Victoria E. Mielgo1, Elena Gastiasoro1, Xabier Murgia1, Hector Lafuente1, Estibaliz Ruiz-del-Yerro1, Adolf Valls-i-Soler2, Enrique Hilario3 and Francisco J. Alvarez1
  • 1 Research Unit on Experimental Respiratory Physiology, Cruces Hospital, Bizkaia, Spain
  • 2 Department of Pediatrics. Cruces Hospital, Bizkaia, Spain
  • 3 Department of Cell Biology and Histology, University of the Basque Country, Bizkaia, Spain

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.

Keywords: hypoxic–ischemic injury, total and regional cerebral blood flow, apoptosis, premature fetal lamb, perinatal life

Citation: Rey-Santano C, Mielgo VE, Gastiasoro E, Murgia X, Lafuente H, Ruiz-del-Yerro E, Valls-i-Soler A, Hilario E and Alvarez FJ (2011) Early cerebral hemodynamic, metabolic, and histological changes in hypoxic–ischemic fetal lambs during postnatal life. Front. Neurosci. 5:111. doi: 10.3389/fnins.2011.00111

Received: 25 January 2011; Accepted: 29 August 2011;
Published online: 20 September 2011.

Edited by:

Laszlo Acsady, Institute of Experimental Medicine, Hungary

Reviewed by:

José Miguel Blasco Ibáñez, University of Valencia, Spain
Aldina Venerosi, Istituto Superiore di Sanità, Italy

Copyright: © 2011 Rey-Santano, Mielgo, Gastiasoro, Murgia, Lafuente, Ruiz-del-Yerro, Valls-i-Soler, Hilario and Alvarez. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Carmen Rey-Santano, Research Unit on Experimental Physiology, Cruces Hospital, Plaza de Cruces s/n, Barakaldo E-48903, Bizkaia, Spain. e-mail: macarmen.reysantano@osakidetza.net