挥发性麻醉药神经保护机制教材.pdfVIP

Anesthesiology 2005; 102:606–15 © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams Wilkins, Inc. Isoflurane Neuroprotection in Hypoxic Hippocampal Slice Cultures Involves Increases in Intracellular Ca2 and Mitogen-activated Protein Kinases Jonathan J. Gray, B.S.,* Philip E. Bickler, M.D., Ph.D.,† Christian S. Fahlman, Ph.D.,‡ Xinhua Zhan, M.D., Ph.D., ‡ Jennifer A. Schuyler, B.S.* Background: The volatile anesthetic isoflurane reduces acute Compared with nitrous oxide–fentanyl anesthesia, isoflu- and delayed neuron death in vitro models of brain ischemia, an rane results in less death of hippocampal neurons 5 days action that the authors hypothesize is related to moderate in- 2 after forebrain ischemia in rats, but after 3 months, this creases in intracellular calcium concentration ([Ca ] ). Specif- i 4 ically, the authors propose that during hypoxia, moderate in- difference is absent. Identification of the basis for this creases in [Ca2]i in the presence of isoflurane stimulates the early, but not late, neuroprotection is of interest because Ca2-dependent phosphorylation of members of the mitogen- it may be possible to devise treatments to extent the activated protein kinase (MAP) kinase Ras-Raf-MEK-ERK path- benefit further into the postischemic recovery period. way that are critical for neuroprotective signaling and suppres- sion of apoptosis. Most of the mechanisms proposed for the protective Methods: Death of CA1, CA3, and dentate neurons in rat qualities of isoflurane observed