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Preterm birth can also be associated with injury to the developing brain and affect the normal trajectory of brain growth. This review will focus on the effects that episodes of perinatal hypoxia (acute, chronic, associated with inflammation or as an antecedent of preterm birth) can have on the developing brain. In animal models of these conditions we have found that relatively brief (acute) periods of fetal hypoxemia can have significant effects on the fetal brain, for example death of susceptible neuronal populations (cerebellum, hippocampus, cortex) and cerebral white matter damage. Chronic placental insufficiency which includes fetal hypoxemia, nutrient restriction and altered endocrine status can result in fetal growth restriction and long\u2010term deficits in neural connectivity in addition to altered postnatal function, for example in the auditory and visual systems. Maternal\/fetal inflammation can result in fetal brain damage, particularly but not exclusively in the white matter; injury is more pronounced when associated with fetal hypoxemia. In the baboon, in which the normal trajectory of growth is affected by preterm birth, there is a direct correlation between a higher flux in oxygen saturation and a greater extent of neuropathological damage. Currently, the only established therapy for neonatal encephalopathy in full term neonates is moderate hypothermia although this only offers some protection to moderately but not severely affected brains. There is no accepted therapy for injured preterm brains. Consequently the search for more efficacious treatments continues; we discuss neuroprotective agents (erythropoietin, N\u2010acetyl cysteine, melatonin, creatine, neurosteroids) which we have trialed in appropriate animal models. The possibility of combining hypothermia with such agents or growth factors is now being considered. A deeper understanding of causal pathways in brain injury is essential for the development of efficacious strategies for neuroprotection.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2011.04.004","type":"journal-article","created":{"date-parts":[[2011,4,19]],"date-time":"2011-04-19T12:22:54Z","timestamp":1303215774000},"page":"551-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":172,"title":["The biological basis of injury and neuroprotection in the fetal and neonatal brain"],"prefix":"10.1002","volume":"29","author":[{"given":"Sandra","family":"Rees","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Melbourne Parkville Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology Monash University Clayton Vic. 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Walker","sequence":"additional","affiliation":[{"name":"Monash Institute of Medical Research Melbourne Vic. 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,15]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"CD004868","article-title":"Late erythropoietin for preventing red blood cell transfusion in preterm and\/or low birth weight infants (Review)","volume":"3","author":"Aher S.","year":"2006","journal-title":"Cochrane Database Syst. 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