PT  - JOURNAL ARTICLE
AU  - Frances J. Northington
AU  - Donna M. Ferriero
AU  - Debra L. Flock
AU  - Lee J. Martin
TI  - Delayed Neurodegeneration in Neonatal Rat Thalamus after Hypoxia–Ischemia Is Apoptosis
AID  - 10.1523/JNEUROSCI.21-06-01931.2001
DP  - 2001 Mar 15
TA  - The Journal of Neuroscience
PG  - 1931--1938
VI  - 21
IP  - 6
4099  - http://www.jneurosci.org/content/21/6/1931.short
4100  - http://www.jneurosci.org/content/21/6/1931.full
SO  - J. Neurosci.2001 Mar 15; 21
AB  - Brain injury in newborns can cause deficits in motor and sensory function. In most models of neonatal brain injury, thalamic damage often occurs. Using the Rice–Vannucci model of neonatal hypoxic–ischemic brain injury, we have shown that neuronal degeneration in somatosensory thalamus is delayed in onset (∼24 hr) compared with cortical and striatal injury and exhibits prominent structural features of apoptosis. In the present study, we examined whether cell death in the thalamus has molecular features of apoptosis. Fas death receptor protein expression increased rapidly after neonatal hypoxia–ischemia, in concert with cleavage of procaspase 8 to its active form. Concurrently, the levels of Bax in mitochondrial-enriched cell fractions increase, and cytochrome c accumulates in the soluble fraction. Mitochondria accumulate in a perinuclear distribution by 6 hr after hypoxia–ischemia. Cytochrome oxidase subunit 1 protein levels also increase at 6 hr after hypoxia–ischemia. Increased levels of Fas death receptor, Bax, and cytochrome c, activation of caspase 8, and abnormalities in mitochondria in the thalamus significantly precede the activation of caspase 3 and the appearance of neuronal apoptosis at 24 hr. We conclude that the delayed neurodegeneration in neonatal rat ventral basal thalamus after hypoxic–ischemic injury is apoptosis mediated by death receptor activation.