Desflurane and sevoflurane attenuate oxygen and glucose deprivation-induced neuronal cell death.

Neuronal cell death may occur via two pathways: those causing necrosis or those causing apoptosis. Apoptosis can be activated during periods of stress such as oxygen and glucose deprivation. Anesthetic agents such as desflurane or sevoflurane can attenuate early neuronal necrotic death, but their effect on oxygen and glucose deprivation-induced apoptosis has not been investigated. Neuronal cell cultures were prepared from neonatal rat cortex and were used between 10 and 14 days in vitro. The neuronal cell cultures were pretreated 30 minutes prior to oxygen and glucose deprivation with either desflurane or sevoflurane (N = 18). Three concentrations of each anesthetic were evaluated. The cultures were then deprived of oxygen and glucose for 30, 60, or 90 minutes. Treatment with desflurane or sevoflurane was continued during the period of oxygen and glucose deprivation. Forty-eight hours after exposure, the cells were examined for apoptosis using TUNEL and DNA gel electrophoresis. Comparisons were made to neuronal cortical cell cultures exposed to oxygen and glucose deprivation alone (N = 9). This in vitro model of oxygen and glucose deprivation was successful in producing neuronal cell death during the exposure times examined. During 30-, 60-, and 90-minute periods of oxygen and glucose deprivation, both desflurane and sevoflurane significantly ( approximately 98%) attenuated neuronal cell death regardless of concentration.

Oxygen and glucose deprivation-induced neuronal apoptosis is attenuated by halothane and isoflurane.

UNLABELLED: Both in vitro and in vivo evidence supports the reduction of early ischemic, both global and focal, brain injury by volatile anesthetics. However, the protection afforded by volatile anesthetics in later neuronal death, i.e., apoptosis, caused by global ischemia has not been investigated. We induced oxygen and glucose deprivation in neuronal cortical cell cultures prepared from newborn rats on in vitro Days 10-14. This hypoxic (PO2 <50 mm Hg) condition was maintained continuously (30, 60, and 90 min). In a separate experiment, the neuronal cell cultures were exposed to isoflurane (1.13%, 2.3%, or 3.3%) or halothane (1.7%, 3.4%, or 5.1%) before oxygen and glucose deprivation, with continued exposure to isoflurane or halothane during oxygen and glucose deprivation. After 48 h, neuronal apoptosis was assessed with terminal deoxynucleotidyl transferase-mediated in situ nick-end labeling and DNA gel electrophoresis. Oxygen and glucose deprivation (30, 60, and 90 min) caused significant apoptosis of cerebral cortical cultured neurons. However, pretreatment and continued treatment during the period of oxygen and glucose deprivation with halothane or isoflurane resulted in a concentration-dependent attenuation of oxygen and glucose deprivation-induced neuronal apoptosis. IMPLICATIONS: This is the first investigation to evaluate the effect of volatile anesthetics on oxygen and glucose deprivation-induced neuronal apoptosis. Oxygen and glucose deprivation-induced neuronal apoptosis can be decreased by prior and continued administration of halothane or isoflurane.