A Rat Model of Perinatal Seizures Provoked by Global Hypoxia

Hypoxic-ischemic encephalopathy (HIE) refers to acute brain injury that results from perinatal asphyxia. HIE is a major cause of neonatal seizures, and outcomes can range from apparent recovery to severe cognitive impairment, cerebral palsy, and epilepsy. Acute partial seizures frequently aid in indicating the severity and localization of brain injury. However, evidence also suggests that the occurrence of seizures further increases the likelihood of epilepsy in later life regardless of the severity of the initial injury. Here, we describe a neonatal rat model of seizure-provoking mild hypoxia without overt brain injury that has been used to investigate potential epileptogenic effects of hypoxia-associated seizures alone on neonatal brain development. Clinically, HIE is defined by brain injury, and thus, this model is not intended to mimic clinical HIE. Rather, its utility is in providing a model to understand the dynamic and long-term regulation of brain function and how this can be perturbed by early life seizures that are provoked by a commonly encountered pathophysiological trigger. Additionally, the model allows the study of brain pathophysiology without the potential confound of variable neuroanatomical changes that are reactive to widespread cell death.