Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain

Age dependency of apoptotic neurodegeneration was studied in the developing rat brain after percussion head trauma. In 7-day-old rats, mechanical trau ma, applied by means of a weight drop device, was shown to trigger widespre ad cell death in the hemisphere ipsilateral to the trauma site, which first appeared at 6 hours, peaked at 24 hours, and subsided by 5 days after trau ma. Ultrastructurally, degenerating neurons displayed features consistent w ith apoptosis. A decrease of bcl-2 in conjunction with an increase of c-jun mRNA levels, which were evident at 1 hour after trauma and were accompanie d by elevation of CPP 32-like proteolytic activity and oligonucleosomes in vulnerable brain regions, confirmed the apoptotic nature of this process, S everity of trauma-triggered apoptosis in the brains of 3- to 30-day-old rat s was age dependent, was highest in 3- and 7-day-old animals, and demonstra ted a subsequent rapid decline. Adjusting the mechanical force in accordanc e with age-specific brain weights revealed a similar vulnerability profile. Thus, apoptotic neurodegeneration contributes in an age-dependent fashion to neuropathological outcome after head trauma, with the immature brain bei ng exceedingly vulnerable. These results help explain unfavorable outcomes of very young pediatric head trauma patients and imply that, in this group, an antiapoptotic regimen may constitute a successful neuroprotective appro ach.