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These changes lead to severe neurological deficits and mortality. Sublethal hypoxic preconditioning (HPC) can protect the developing brain against H\/I. However, limited evidence is available concerning its effect on white matter injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, P6 neonatal Sprague\u2010Dawley rats were subjected to normoxic (21% O<jats:sub>2<\/jats:sub>) or HPC (7.8% O<jats:sub>2<\/jats:sub>) for 3\u00a0hours followed 24\u00a0hours later by H\/I brain injury. Neurological deficits were assessed by gait, righting reflex, foot fault, and Morris water maze tests. Compound action potential of the corpus callosum was recorded 35\u00a0days after surgery, and the correlation between axon myelination and neurological function was determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypoxic preconditioning significantly attenuated H\/I brain injury at 7\u00a0days and remarkably improved both sensorimotor and cognitive functional performances up to 35\u00a0days after H\/I. HPC\u2010afforded improvement in long\u2010term neurological outcomes was attributable, at least in part, to restoration of the differentiation and maturation capacity in oligodendrocyte progenitor cells, amelioration of microglia\/macrophage activation and neuroinflammation, and continuation of brain development after H\/I.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Hypoxic preconditioning restores white matter repair, development, and functional integrity in developing brain after H\/I brain injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13102","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T21:06:21Z","timestamp":1548709581000},"page":"734-747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hypoxic preconditioning improves long\u2010term functional outcomes after neonatal hypoxia\u2013ischemic injury by restoring white matter integrity 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