title: Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury.
abstract: OBJECTIVE
  Periventricular white matter injury (PWMI) is the major cause of cerebral palsy and cognitive impairment in prematurely born infants. PWMI is characterized by reductions in cerebral myelination and cerebrocortical volumes and is associated with secondary ventriculomegaly. In neonatal rodents, these features of PWMI can be induced by rearing in chronic hypoxia or by activation of A1 adenosine receptors. We determined: (1) whether altered maturation or development of one or more oligodendrocyte (OL) lineage stages plays a role in the pathogenesis of the myelination disturbances associated with exposure to chronic hypoxia, and (2) whether blockade of A1 adenosine receptor action with the adenosine antagonist caffeine can prevent hypoxia-induced white matter injury.
  
  
  METHODS
  Ventriculomegaly and reduced cerebral myelination were generated in mice reared in hypoxia (10% oxygen) from postnatal days 3 (P3) through 12.
  
  
  RESULTS
  Hypomyelination was related to abnormal OL lineage progression and a reduction in the OL progenitor pool. Myelination was enhanced and ventriculomegaly reduced in hypoxia-exposed neonatal pups treated with caffeine from P3 to P12.
  
  
  CONCLUSIONS
  These observations support that hypoxia inhibits OL maturation and that caffeine administration during early postnatal development may have utility in the prevention of PWMI.
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Back
authors.forename: Andrew
authors.initials: A
authors.lastname: Craig
authors.forename: Ning Ling
authors.initials: NL
authors.lastname: Luo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ren
authors.forename: Ravi Shankar
authors.initials: RS
authors.lastname: Akundi
authors.forename: Ivy
authors.initials: I
authors.lastname: Ribeiro
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors / Q000378:metabolism; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; D002110:Caffeine; D000241:Adenosine