Article, 2024

Enteral plasma supports brain repair in newborn pigs after birth asphyxia

Brain Behavior and Immunity, ISSN 1090-2139, 0889-1591, Volume 119, Pages 693-708, 10.1016/j.bbi.2024.04.032

Contributors

Ventura, Gemma Chavarria 0009-0005-4396-797X [1] Dyshliuk, Nadiya [1] [2] Dmytriyeva, Oksana 0000-0002-2075-338X [1] Nordsten, Mads Jacob Bagi 0000-0002-6195-9894 [1] Haugaard, Maria Mathilde [1] Christiansen, Line Iadsatian 0000-0002-0339-0302 [1] Thymann, Thomas 0000-0001-7480-6064 [1] Sangild, Sangild Per 0000-0002-5462-7760 [1] [3] [4] Pankratova, Stanislava 0000-0002-5406-5163 (Corresponding author) [1]

Affiliations

  1. [1] University of Copenhagen
    2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] National University of Life and Environmental Sciences of Ukraine
    3. [NORA names: Ukraine; Europe, Non-EU];
  3. [3] Odense University Hospital
    4. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  4. [4] Rigshospitalet
    5. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]

Abstract

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia. Mild birth asphyxia was induced by temporary occlusion of the umbilical cord prior to caesarean delivery. Motor development was assessed in asphyxiated (ASP) and control (CON) piglets using neonatal arousal, physical activity and gait test parameters before euthanasia on Day 4. The ASP pigs exhibited increased plasma lactate at birth, deficient motor skills and increased glial fibrillary acidic protein levels in CSF and astrogliosis in the putamen. The expression of genes related to oxidative stress, inflammation and synaptic functions was transiently altered in the motor cortex and caudate nucleus. The number of apoptotic cells among CTIP2-positive neurons in the motor cortex and striatal medium spiny neurons was increased, and maturation of preoligodendrocytes in the internal capsule was delayed. Plasma supplementation improved gait performance in the beam test, attenuated neuronal apoptosis and affected gene expression related to neuroinflammation, neurotransmission and antioxidants (motor cortex, caudate). We present a new clinically relevant animal model of moderate birth asphyxia inducing structural and functional brain damage. The components in plasma that support brain repair remain to be identified but may represent a therapeutic potential for infants and animals after birth asphyxia.

Keywords

Asp, CSF, activity, animal models, animals, antioxidants, apoptosis, apoptotic cells, arousal, asphyxia, astrogliosis, attenuated neuronal apoptosis, beam, beam test, birth, birth asphyxia, blood flow, brain, brain damage, brain outcomes, brain repair, caesarean delivery, capsule, caudate, caudate nucleus, cells, clinic, clinically relevant animal model, components, control, cortex, damage, day 4, days, deficient blood flow, deficient motor skills, delivery, development, encephalopathy, euthanasia, expression, expression of genes related to oxidative stress, flow, function, functional brain damage, gait, gait performance, genes related to oxidative stress, glial fibrillary acidic protein levels, hypoxic-ischaemic encephalopathy, immunomodulatory components, increased plasma lactate, infants, inflammation, internal capsule, lack, lack of oxygen, lactate, levels, maturation, medium spiny neurons, mild birth asphyxia, model, moderate birth asphyxia, motor, motor cortex, motor development, motor skills, neonatal arousal, neuroinflammation, neurological damage, neuronal apoptosis, neurons, neurotransmission, newborn pigs, newborns, nucleus, occlusion, outcomes, oxidative stress, oxygen, parameters, performance, physical activity, piglets, pigs, plasma, plasma lactate, plasma supplementation, potential, preoligodendrocytes, protein levels, putamen, relevant animal models, repair, response, skills, spiny neurons, stress, striatal medium spiny neurons, supplementation, synaptic function, temporary occlusion, test, test parameters, therapeutic potential

Funders

  • Takeda (United States)
  • Carlsberg Foundation

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