Effect of hyperoxic resuscitation on propensity of germinal matrix haemorrhage and cerebral injury C. O. Chua*†, G. Vinukonda*‡, F. Hu‡, N. Labinskyy§, M. T. Zia*, J. Pinto¶, A. Csiszar§, Z. Ungvari§ and P. Ballabh*‡ Departments of *Pediatrics, ‡Cell Biology and Anatomy, and ¶Biochemistry, NewYork Medical College-Westchester Medical Center,Valhalla, NewYork, §Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma, Oklahoma, and †JanetWeis Children’s Hospital at Geisinger Medical Center, Danville, Pennsylvania, USA C. O. Chua, G. Vinukonda, F. Hu, N. Labinskyy, M.T. Zia, J. Pinto, A. Csiszar, Z. Ungvari and P. Ballabh (2010) Neuropathology and Applied Neurobiology 36, 448–458 Effect of hyperoxic resuscitation on propensity of germinal matrix haemorrhage and cerebral injury Aims: Intraventricular haemorrhage (IVH) and cerebral injury are major neurological disorders of premature infants. The effect of hyperoxic resuscitation on the occur- rence of IVH and cerebral injury is elusive. Therefore, we asked whether hyperoxia during neonatal resuscitation increased the incidence and severity of IVH and cerebral injury in premature newborns. Methods: Premature rabbit pups, delivered by C-section, were sequentially assigned to receive 100%, 40% or 21% oxygen for 15 or 60 min at birth. The pups were treated with intraperito- neal glycerol at 24-h postnatal age to determine the inci- dence and severity of glycerol-induced IVH. Vascular endothelial growth factor and angiopoietin-2 genes and protein expression, endothelial proliferation as well as free radical levels and antioxidants were assessed in the germi- nal matrix, white matter and cortex of pups exposed to 100% oxygen and to 21% oxygen. Results: Exposure with 100% oxygen for 1 h did not adversely exacerbate the inci- dence of glycerol-induced IVH in premature rabbit pups. Compared with room air, 100% oxygen enhanced mRNA expression of both vascular endothelial growth factor and angiopoietin-2 as well as reactive oxygen species levels in the germinal matrix. Hyperoxia did not affect endothelial proliferation, apoptosis or neuronal degeneration in the forebrain. Conclusion: Our data suggest that 100% oxygen exposure for 1 h does not increase the risk of IVH or cerebral injury in premature rabbit pups. Although extrapolating rabbit neural developmental data into humans has obvious limitations, we speculate that hyper- oxia of short duration at birth in premature infants may not result in major neurological adverse effects. Keywords: apoptosis, cerebral injury, hyperoxia, intraventricular haemorrhage, neonatal resuscitation, reactive oxygen species Introduction The American Academy of Pediatrics recommends resus- citation of both preterm and term newborn infants with 100% O2 [1]. The practice of using 100% O2 to resuscitate premature newborns has been challenged by a number of animal and human studies [2]. Indeed, both the efficacy and safety of neonatal resuscitation with 100% vs. 21% O2 have been controversial [3]. Hence, it is crucial to deter- mine the impact of hyperoxic resuscitation on the brain and other organ systems. The common neurological com- plications of prematurity are germinal matrix haemor- rhage (GMH)-intraventricular haemorrhage (IVH) and periventricular leukomalacia; and their incidence as well as severity can be influenced by the concentration of O2 used during neonatal resuscitation. Therefore, we Correspondence: Caroline O. Chua, Janet Weis Children’s Hospital at Geisinger Medical Center, 100 N. Academy Avenue, Danville, PA 17822, USA. Tel: +1 570 271 8091; Fax: +1 570 271 5879; E-mail: carolineochua@yahoo.com; cochua@geisinger.edu 448 © 2010 Blackwell Publishing Ltd Neuropathology and Applied Neurobiology (2010), 36, 448–458 doi: 10.1111/j.1365-2990.2010.01087.x