Lorena Barata1, Alberto Cabañas2, Hector Lafuente3, Carlos Vargas1, María Ceprián4, Leticia Campa5, Laura Jiménez-Sánchez2, M Ruth Pazos6, Francisco-José Alvarez3, José Martínez-Orgado7. 1. Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. 2. Instituto de Investigación Puerta de Hierro Majadahonda, Madrid, Spain. 3. BioCruces, Gurutzetako Ospitalea, Barakaldo, Bizkaia, Spain. 4. Departamento de Bioquímica y Biología Molecular, CIBERNED, IRICYS, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. 5. CSIC-Instituto de Investigaciones Biomedicas de Barcelona (IIBB), IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. 6. Laboratorio de Apoyo a la Investigación, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 7. Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. jose.martinezo@salud.madrid.org.
Abstract
BACKGROUND: Newborn pigs offer theoretical advantages for studying newborn hypoxic-ischemic (HI) brain damage because of a development and structure similar to the human brain. However, the correlation between functional features and actual HI brain damage has not been reported. METHODS: Newborn pigs were examined daily for 3 days after a HI insult using amplitude-integrated EEG (aEEG), and a neurobehavioral score enriched with stress and social and object interaction-driven activity evaluation. Brain damage was then assessed using histologic, immunohistochemical, and proton magnetic resonance spectroscopy studies. Brain concentration of several neurotransmitters was determined by HPLC. RESULTS: HI insult led to aEEG amplitude decrease, muscle tone and activity impairment, eating disorders, poor environmental interaction, and increased motionless periods. Basal aEEG amplitude, muscle tone, and general behavior were the best predictive items for histological and biochemical (lactate/N-acetylaspartate ratio) brain damage. Hyperexcitable response to stress correlated inversely with brain damage. Motionless time, which correlated with brain damage severity, was inversely related to brain concentration of dopamine and norepinephrine. CONCLUSION: Standard neurologic examination of brain activity and motor and behavioral performance of newborn pigs is a valuable tool to assess HI brain damage, thus offering a powerful translational model for HI brain damage pathophysiology and management studies.
BACKGROUND: Newborn pigs offer theoretical advantages for studying newborn hypoxic-ischemic (HI) brain damage because of a development and structure similar to the human brain. However, the correlation between functional features and actual HI brain damage has not been reported. METHODS: Newborn pigs were examined daily for 3 days after a HI insult using amplitude-integrated EEG (aEEG), and a neurobehavioral score enriched with stress and social and object interaction-driven activity evaluation. Brain damage was then assessed using histologic, immunohistochemical, and proton magnetic resonance spectroscopy studies. Brain concentration of several neurotransmitters was determined by HPLC. RESULTS: HI insult led to aEEG amplitude decrease, muscle tone and activity impairment, eating disorders, poor environmental interaction, and increased motionless periods. Basal aEEG amplitude, muscle tone, and general behavior were the best predictive items for histological and biochemical (lactate/N-acetylaspartate ratio) brain damage. Hyperexcitable response to stress correlated inversely with brain damage. Motionless time, which correlated with brain damage severity, was inversely related to brain concentration of dopamine and norepinephrine. CONCLUSION: Standard neurologic examination of brain activity and motor and behavioral performance of newborn pigs is a valuable tool to assess HI brain damage, thus offering a powerful translational model for HI brain damage pathophysiology and management studies.
Authors: Lorena Barata; María de Hoz-Rivera; Angela Romero; María Martínez; Laura Silva; María Villa; Leticia Campa; Laura Jiménez-Sánchez; José Martínez-Orgado Journal: Front Pharmacol Date: 2022-07-18 Impact factor: 5.988
Authors: Luis Martinez-Ramirez; Andrea Slate; George Price; Ann-Christine Duhaime; Kevin Staley; Beth A Costine-Bartell Journal: eNeuro Date: 2022-06-10