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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357895
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$58,239
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Su, Weiping; Foster, Scott C; Xing, Rubing et al. (2017) CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation. J Biol Chem 292:4434-4445
Lima, Fernanda B; Leite, Cristiane M; Bethea, Cynthia L et al. (2017) Progesterone increased ?-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration. Brain Res 1663:1-8
Slayden, Ov Daniel (2016) Translational In Vivo Models for Women's Health: The Nonhuman Primate Endometrium--A Predictive Model for Assessing Steroid Receptor Modulators. Handb Exp Pharmacol 232:191-202
Chadderdon, S M; Belcik, J T; Bader, L et al. (2016) Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes (Lond) 40:1600-1603
Dufour, Brett D; McBride, Jodi L (2016) Intravascular AAV9 Administration for Delivering RNA Silencing Constructs to the CNS and Periphery. Methods Mol Biol 1364:261-75
Meyer, Thomas J; Held, Ulrike; Nevonen, Kimberly A et al. (2016) The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery. Genome Biol Evol 8:3209-3225
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C et al. (2016) Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun 7:11138
Sylwester, Andrew; Nambiar, Kate Z; Caserta, Stefano et al. (2016) A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev 158:14-22
Laws, L H; Parker, C E; Cherala, G et al. (2016) Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion. Am J Transplant 16:3139-3149

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