Prenatal systemic hypoxiaischemia: A rat model of neurodevelopmental disorders related to prematurity

• Coq Jacques-Olivier
• Tsuji Masahiro

• GABA
• Gamma-aminobutyric acid
• HI
• Hypoxia-ischemia
• IUGR
• Intrauterine growth restriction
• LBW
• KCC2
• Potassium-chloride cotransporter 2
• MIUH
• NKCC1
• Sodiumpotassium-chloride cotransporter 1
• NDDs
• Neurodevelopmental disorders
• P10
• Postnatal day 10
• PSHI
• Prenatal systemic hypoxia-ischemia
• RUPP
• TSHI
• WMI
• 5-10 intrauterine growth restriction
• Mild intrauterine hypoperfusion
• Reduced uterine perfusion pressure
• Transient systemic hypoxia-ischemia
• Low birth weight
• White matter injury
• Hyperactivity
• Neuroinflammation
• Maladaptive plasticity
• Hyperexcitability AC
• Ameroid constrictors ADHD
• Attention deficit hyperactivity disorder ASD
• Autism spectrum disorder EP
• Encephalopathy of prematurity E17
• Embryonic day 17 GABA
• Gamma-aminobutyric acid HI
• Hypoxia-ischemia IUGR
• Intrauterine growth restriction LBW
• Low birth weight KCC2
• Potassium-chloride cotransporter 2 MIUH
• Mild intrauterine hypoperfusion NKCC1
• Sodiumpotassium-chloride cotransporter 1 NDDs
• Neurodevelopmental disorders P10
• Postnatal day 10 PSHI
• Prenatal systemic hypoxia-ischemia RUPP
• Reduced uterine perfusion pressure TSHI
• Transient systemic hypoxia-ischemia WMI
• Ameroid constrictors
• ADHD
• Attention deficit hyperactivity disorder
• ASD
• Autism spectrum disorder
• EP
• Encephalopathy of prematurity
• E17
• Embryonic day 17

Premature birth represents about 11% of pregnancies overall and is increasing worldwide. The prevalence of brain damage and neurodevelopmental disorders (NDDs) related to prematurity is high and increasing. Etiological factors of perinatal brain injury in preterm children mainly involve exposure to systemic infection/inflammation, hypoxia/ischemia or hyperoxia, placental pathologies, foetal growth restriction or infections, maternal hypotension, hypoxemia, preeclampsia, diabetes, as well as multiple birth, stress, air pollution or drug abuse. Several animal models have been developped to better understand the perinatal etiological factors and mechanisms underlying the emergence of NDDs. Among rat models of prenatal brain injury, mild intrauterine hypoperfusion (MIUH) at embryonic day 17 (E17), transient systemic hypoxia-ischemia (TSHI) at E18, reduced uterine perfusion pressure (RUPP) from E14 and permanent stenosis of uterine arteries at E17 using ameroid constrictors (AC) are gathered here as prenatal systemic hypoxia-ischemia (PSHI). Briefly, these models of PSHI induce intrauterine growth restriction, low birth weight, cardiovascular disease, metabolic syndrome, neuroinflammation, diffuse brain damage including white and gray matter injuries, astrogliosis, hyperexcitability related to homeostatic imbalance of intracellular chloride concentration, musculoskeletal pathologies, sensorimotor disturbances, impaired behavior and cognition, and deficits in executive functions related to maladaptive plasticity and network disorganization in the central nervous system (CNS). These preclinical models point out several mechanisms of action and are promising for developing new strategies of prevention, remediation and rehabilitation of the NDDs related to prematurity.