Journal
BRAIN RESEARCH
Volume 1531, Issue -, Pages 65-74Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2013.07.039
Keywords
Neonatal brain injury; Hypoxia; Activin; HIF; Strain difference
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Funding
- Interdisciplinary Center for Clinical Research, Friedrich-Alexander Universitat Erlangen-Nurnberg
- Jurgen Manchot Stiftung
- Deutsche Forschungsgemeinschaft
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Activin A is a multifunctional growth and differentiation factor with pronounced neuroprotective properties that is strongly up-regulated in various forms of acute brain disorders and injuries including epilepsy, stroke and trauma. In a pediatric context, activin A has been advanced as a potential marker for the severity of perinatal hypoxic-ischemic brain injury. Here we investigated the regulation of activin A under global hypoxia without ischemia in primary cultures of cortical neurons and in neonatal and adult mice of two strains (C57B1/6 and CD-1). From birth to adulthood, activin beta A subunit, activin receptors, and functional activin antagonists were all expressed at roughly similar mRNA levels in the brain of C57B1/6 mice. Independent of mouse line and age, we found both moderate (11% O-2, 2 h) and severe hypoxia (8%, 6 h) to be consistently associated with normal or even reduced levels of activin beta A (Inhba) mRNA. The surprising unresponsiveness of Inhba expression to hypoxia was confirmed at the protein level. In situ hybridization did not indicate regional, hypoxia-related differences in Inhba expression. Pharmacologic stabilization of hypoxia inducible factors with the prolyl hydroxylase inhibitor FG-4497 did not influence Inhba mRNA levels in neonatal mice. Our data indicate that pure hypoxia differs from other, more complex types of brain damage in that it appears not to recruit activin A as an endogenous neuroprotective agent. (C) 2013 Elsevier B.V. All rights reserved.
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