DEVELOPMENTAL NEUROAPOPTOSIS IN NHP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Extensive research has shown that anesthetic agents can produce extensive apoptotic (programmed cell death) neurodegeneration in the developing rodent CNS. The observed degeneration occurs during the synaptogenesis period (the time when neurons establish interconnections). In primates the period encompasses the last trimester of in utero life and the first several months of post-natal life. Humans are commonly exposed to agents, which have been found to produce this damage, in either a clinical or drug abuse setting. Because of the large differences in rodent and human brain structure, it is unknown whether primates might also be susceptible to the same neurotoxic effects of these drugs. Determining whether the damage occurs in primate brain is critically needed. Thus, the broad goal of this research is to examine the neurotoxic potential of these various classes of anesthetic agents in non-human primates. SIGNIFICANCE: Every year millions of human fetuses and infants are exposed to the agents that we have found can trigger neuroapoptosis in the developing brain. In many cases, for example when life-threatening conditions require surgical anesthesia, exposure of the developing brain to apoptogenic drugs, is necessary and unavoidable. Therefore, it is important to determine whether the developing primate brain is susceptible to anesthesia-induced neuroapoptosis and to achieve a better understanding of the underlying mechanisms, learn more about the behavioral consequences and develop methods for preventing both the neuropathological and behavioral consequences. PROGRESS: Significant progress has been made with both the neonatal and fetal nonhuman primate models. Exposure of both the fetal and neonatal rhesus macaque to isoflurane, under clinically relevant conditions, induces widespread neuroapoptosis affecting all divisions of the cerebral cortex.