Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury

被引:158
作者
Back, Stephen A.
Craig, Andrew
Luo, Ning Ling
Ren, Jennifer
Akundi, Ravi Shankar
Ribeiro, Ivy
Rivkees, Scott A.
机构
[1] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA
[2] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA
关键词
D O I
10.1002/ana.21008
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 Al 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 Al 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: Hypomayelination 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. Interpretation: These observations support that hypoxia inhibits OL maturation and that caffeine administration during early postnatal development may have utility in the prevention of PWMI.
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页码:696 / 705
页数:10
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