BRAIN-DAMAGE DUE TO CEREBRAL HYPOXIA ISCHEMIA IN THE NEONATE - PATHOLOGY AND PHARMACOLOGICAL MODIFICATION/

Brain damage due to an episode of cerebral hypoxia/ischemia remains a major problem in the human infant, providing impetus for the testing o f potential neuroprotective agents in animal models. Although these an imal models do not mirror the human pathology exactly (e.g., with resp ect to regions vulnerable to damage), they usually have the histologic al characteristics of gray matter hypoxic/ischemic injury in the human . An important factor in comparing models directly is the stage of dev elopment of the brain al birth, which varies widely between species. A pproaches to prevent or treat cerebral hypoxic/ischemic damage in neon ates have paralleled those in adults. However, most of these results s hould be interpreted cautiously, since neonatal rat models with little concurrent physiological monitoring are often used. As in adults, mod erate hypothermia during the insult or a preconditioning stress prior to the insult has prevented hypoxic/ischemic brain damage. Different f rom adults is the demonstration that pretreatment with moderate doses of glucocorticoids or hyperglycemia during the hypoxic/ischemic insult protects the brain against infarction. Partial protection, primarily in neonatal rats, has also been produced by pretreatment with voltage- sensitive calcium channel antagonists, free radical scavengers, growth factors, gangliosides, anticonvulsants, antiinflammatory agents, and nitric oxide synthase inhibitors. Posttreatment has been effective wit h a few agents. The most consistent has been the protective effect obs erved with glutamate receptor antagonists administered before but also up to 4 h after the insult. The effects of most of these therapies on blood glucose, body temperature, and/or the systemic circulation shou ld be measured and the protective effects confirmed in larger species prior to considering clinical applications.