Experimental models of hypoxic-ischemic encephalopathy: hypoxia-ischemia in the immature rat.

The development of experimental models to study the mechanisms of perinatal hypoxic-ischemic encephalopathy and stroke and effective therapies represents an important goal in perinatal medicine. However, due to the complexity of this pathological condition in humans, to date there is no ideal animal model that completely reproduces this condition. This unit describes the most widely used rodent animal model for the study of hypoxic-ischemic encephalopathy during development. The model consists of 7-day-old pup rats subjected to unilateral carotid artery ligation followed by timed hypoxia exposure, and incorporates both focal cerebral ischemia and reperfusion. Its strength lies in the relative ease of the surgical procedure, the low mortality rate, and the possibility of performing long-term experiments, a necessity for preclinical therapeutic trials. Over the years, this model has been extensively characterized, and most information on the mechanisms responsible for neurodegeneration and possible therapeutic approaches following hypoxia-ischemia during brain development derives from studies performed using this model.