ANIMAL-MODELS FOR THE STUDY OF PERINATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY - A CRITICAL ANALYSIS

We critically evaluated various design features from 292 animal studie s related to perinatal hypoxic-ischemic encephalopathy (HIE). Rodents were the most frequently used animals in HIE research (26%), followed by piglets (23%) and sheep (22%). Asphyxia with or without ischemia wa s the most predominant method of producing experimental brain damage, but there were significant variations in specific details, particularl y regarding the method and duration of brain insult. In 71% (207/292) of studies the CNS outcomes were tested within 24 h of experimental in sult and in 29% (85/292) they were tested 24 h or more after the insul t. Acute CNS metabolic end-points were assessed in 82-100% of all stud ies. In 90% of studies the chronological age of the animal was equival ent to that of human term newborn infant. However, in only 23% (67/292 ) were clinical neurological, developmental or behavioral outcomes eva luated, and in only 26% (76/292) was neuropathology assessed. While no single animal model was found to be ideal for all HIE research, some models were distinctly superior to others, depending upon the specific research question. The fetal sheep, newborn lamb and piglet models ar e well suited for the study of acute and subacute metabolic and physio logic endpoints, whereas the rodent and primate models could be used f or long-term neurological and behavioral outcome experiments as well. We also feel that standardizing the study design features, including a n HI insult method that produces consistent and predictable brain dama ge is urgently needed. Studies in neuro-ethology should explore how we ll brains of various animals compare with that of the newborn human in fant. There is also a need for developing animal models that mimic cli nical entities in which long-term neuro-developmental and behavioral o utcomes can be assessed. (C) 1997 Elsevier Science Ireland Ltd.