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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01351

Curcumin: novel treatment in neonatal hypoxic-ischaemic brain injury

  • 1Maternal & Fetal Medicine, Perinatal Brain Repair Group, Institute for Women’s Health, Faculty of Population Health Sciences, University College London, United Kingdom
  • 2Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden
  • 3Maternal & Fetal Medicine, Perinatal Brain Repair Group, UCL Institute for Women's Health, United Kingdom
  • 4Glaucoma and Retinal Neurodegeneration Group, Department of Visual Neuroscience,, Institute of Ophthalmology, Faculty of Brain Sciences, University College London, United Kingdom
  • 5Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, United Kingdom

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. There is therefore an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE.
Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumour and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilise the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects.
Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200µg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60min or 120min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin’s anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity.
In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

Keywords: Curcumin, hypoxia, ischaemia, Neuroprotection, neonate, Oxidative Stress

Received: 26 Jan 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Rocha-Ferreira, Sisa, Bright, Fautz, Harris, Contreras Riquelme, Agwu, Kurulday, Mistry, Hill, Lange and Hristova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mariya Hristova, Institute for Women’s Health, Faculty of Population Health Sciences, University College London, Maternal & Fetal Medicine, Perinatal Brain Repair Group, London, WC1E 6AU, England, United Kingdom, m.hristova@ucl.ac.uk