Transient occlusion of uterine arteries and intra-amniotic injection of lipopolysaccharide in rats as a model of cerebral palsy

Cerebral palsy (CP) is the most common sensorimotor disability in childhood. Understanding the molecular mechanisms mediating inflammation in the placental–fetal–brain axis is of great clinical importance, but in order to do so, rigorous and translational animal models need to be used. This animal model that combines transient systemic HI (TSHI) and intra-amniotic lipopolysaccharide (LPS) administration in pregnant rats recapitulates the complex abnormalities seen clinically in infants with perinatal brain injury leading to CP, allowing it to be used to uncover novel mechanisms of injury in this exceedingly vulnerable patient population. Unlike other models, it encompasses an intact maternal–placental–fetal–brain axis. Deficits in this model occur through adulthood and closely match both functional and biochemical deficits seen in humans with CP through the lifespan. This animal model also results in neural injury and persistent immune dysregulation in adult offspring, including complex gait abnormalities, impaired social interaction, motor inhibition, and executive function.