Delayed neurodegeneration in neonatal rat thalamus after hypoxia-ischemia is apoptosis

Brain injury in newborns can cause deficits in motor and sensory function. In most models of neonatal brain injury, thalamic damage often occurs. Usin g the Rice-Vannucci model of neonatal hypoxic-ischemic brain injury, we hav e shown that neuronal degeneration in somatosensory thalamus is delayed in onset (similar to 24 hr) compared with cortical and striatal injury and exh ibits prominent structural features of apoptosis. In the present study, we examined whether cell death in the thalamus has molecular features of apopt osis. Fas death receptor protein expression increased rapidly after neonata l hypoxia-ischemia, in concert with cleavage of procaspase 8 to its active form. Concurrently, the levels of Bax in mitochondrial-enriched cell fracti ons increase, and cytochrome c accumulates in the soluble fraction. Mitocho ndria accumulate in a perinuclear distribution by 6 hr after hypoxia-ischem ia. Cytochrome oxidase subunit 1 protein levels also increase at 6 hr after hypoxia-ischemia. Increased levels of Fas death receptor, Bax, and cytochr ome c, activation of caspase 8, and abnormalities in mitochondria in the th alamus significantly precede the activation of caspase 3 and the appearance of neuronal apoptosis at 24 hr. We conclude that the delayed neurodegenera tion in neonatal rat ventral basal thalamus after hypoxic-ischemic injury i s apoptosis mediated by death receptor activation.