Article, 2024

Enteral plasma supports brain repair in newborn pigs after birth asphyxia

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

Contributors

Ventura G.C. [1] Dyshliuk N. [1] [2] Dmytriyeva O. 0000-0002-2075-338X [3] Nordsten M.J.B. [1] Haugaard M.M. [1] Christiansen L.I. [1] Thymann T. 0000-0001-7480-6064 [1] Sangild P.T. 0000-0002-5462-7760 [1] [4] [5] Pankratova S. 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];
  3. [2] National University of Life and Environmental Sciences of Ukraine
  4. [NORA names: Ukraine; Europe, Non-EU];
  5. [3] University of Copenhagen
  6. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  7. [4] Odense University Hospital
  8. [NORA names: Region of Southern Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  9. [5] Rigshospitalet
  10. [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

Birth asphyxia, Caudate nucleus, Motor cortex, Motor development, Plasma

Funders

  • Takeda Pharmaceuticals U.S.A.
  • Carlsbergfondet

Data Provider: Elsevier