title: Animal models of perinatal asphyxia: contributions, contradictions, clinical relevance.
abstract: Animal models have contributed immensely to our understanding of hypoxic ischemic encephalopathy in the newborn. A number of animal models have been used, including both primate and subprimate species. Although the Rhesus monkey model has a dramatically similar pathological distribution of brain injury when compared with the human, other pathologic processes secondary to asphyxia may be more appropriately assessed in other species. The maxim that because primates are closer on the phylogenetic tree to humans than are subprimates all observations in the primate are applicable to the human is simply not true. Understanding of the neurochemical consequences of asphyxia in the past decade have arisen from experiments primarily in the neonatal rat. We have come to understand that not only is the hypoxic event of major significance, but that, once reperfused, reoxygenation causes further injury. Free-radical generation following reperfusion may be massive and may further contribute to cell membrane injury. These observations have lead to rational theoretic approaches to the treatment of hypoxic ischemic brain injury. On the other hand, previously used treatments such as osmotic agents and glucocorticoids would appear to be not only inefficacious but hazardous in the treatment of hypoxic ischemic brain injury. The role of nitric oxide (NO) in the pathogenesis of brain injury is yet uncertain, but there is little doubt that it plays a significant role. Although survival of the immature animal subjected to hypoxic environment is longer than in the mature animal, the central nervous system of the immature animal is more sensitive to glutamate and N-Methyl-D-aspartate (NMDA) receptor-mediated injury.
authors.affiliation: Division of Child Neurology, Children's Hospital of Pittsburgh, PA 15213, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Painter
mesh_terms: D000142:Acidosis, Respiratory / Q000150:complications / Q000503:physiopathology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000150:complications / Q000503:physiopathology; D001930:Brain Injuries / Q000151:congenital* / Q000209:etiology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications / Q000151:congenital* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005311:Fetal Hypoxia / Q000150:complications / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008253:Macaca mulatta; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology
chemical_list: D005609:Free Radicals; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D000255:Adenosine Triphosphate