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Docosahexaenoic Acid Reduces Cerebral Damage and Ameliorates Long-Term Cognitive Impairments Caused by Neonatal Hypoxia–Ischemia in Rats

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Abstract

As the interest in the neuroprotective possibilities of docosahexaenoic acid (DHA) for brain injury has grown in the recent years, we aimed to investigate the long-term effects of this fatty acid in an experimental model of perinatal hypoxia–ischemia in rats. To this end, motor activity, aspects of learning, and memory function and anxiety, as well as corticofugal connections visualized by using tracer injections, were evaluated at adulthood. We found that in the hours immediately following the insult, DHA maintained mitochondrial inner membrane integrity and transmembrane potential, as well as the integrity of synaptic processes. Seven days later, morphological damage at the level of the middle hippocampus was reduced, since neurons and myelin were preserved and the astroglial reactive response and microglial activation were seen to be diminished. At adulthood, the behavioral tests revealed that treated animals presented better long-term working memory and less anxiety than non-treated hypoxic–ischemic animals, while no difference was found in the spontaneous locomotor activity. Interestingly, hypoxic–ischemic injury caused alterations in the anterograde corticofugal neuronal connections which were not so evident in rats treated with DHA. Thus, our results indicate that DHA treatment can lead to long-lasting neuroprotective effects in this experimental model of neonatal hypoxia–ischemic brain injury, not only by mitigating axonal changes but also by enhancing cognitive performance at adulthood.

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Acknowledgments

Funding was provided by the Basque Government (IT 773/13 and BFI-2011-129) and by the University of the Basque Country (UPV/EHU, recruitment of recent doctors). The authors wish to thank the SGIker of the University of the Basque Country for providing technical and human support.

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Authors and Affiliations

  1. Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, E-48940, Leioa, Spain

    Olatz Arteaga, M. Revuelta, E. Hilario & A. Álvarez

  2. Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

    L. Urigüen

  3. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    L. Urigüen

  4. Department of Neuroscience, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

    L. Martínez-Millán

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  1. Olatz Arteaga
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  2. M. Revuelta
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Arteaga, O., Revuelta, M., Urigüen, L. et al. Docosahexaenoic Acid Reduces Cerebral Damage and Ameliorates Long-Term Cognitive Impairments Caused by Neonatal Hypoxia–Ischemia in Rats. Mol Neurobiol 54, 7137–7155 (2017). https://doi.org/10.1007/s12035-016-0221-8

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