Early neurodegeneration after hypoxia-ischemia in neonatal rat is necrosiswhile delayed neuronal death is apoptosis

We used silver staining to demonstrate neuronal cell body, axonal, and term inal degeneration in brains from p7 rat pups recovered for 0, 1.5, 3, 6, 24 , 48, 72 h, and 6 days following hypoxia-ischemia. We found that initial in jury is evident in ipsilateral forebrain by 3 h following hypoxia-ischemia, while injury in ventral basal thalamus develops at 24 h. A secondary phase of injury occurs at 48 h in ipsilateral cortex, but not until 6 days in ba sal ganglia. Initial injury in striatum and cortex is necrosis, but in thal amus the neurodegeneration is primarily apoptosis. Degeneration also occurs in bilateral white matter tracts, and in synaptic terminal fields associat ed with apoptosis in regions remote from the primary injury. These results show that hypoxia-ischemia in the developing brain causes both early and de layed neurodegeneration in specific systems in which the morphology of neur onal death is determined by time, region, and potentially by patterns of ne uronal connectivity. (C) 2001 Academic Press.