Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory.

BACKGROUND: Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue. METHODS: Postnatal day 7 (P7) rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition. RESULTS: Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory. CONCLUSION: Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.

Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females.

Volatile anesthetics are used widely for achieving a state of unconsciousness, yet these agents are incompletely understood in their mechanisms of action and effects on neural development. There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. The explanation for these behavioral changes remains elusive, although acute neuronal death after anesthesia is commonly believed to be a principal cause. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment. However, the assessment of predisposing factors is lacking. We investigated the role of sex by delivering isoflurane to postnatal day (P)7 male and female Sprague Dawley rats for 4 h. Brain cell death was assessed 12 h later using FluoroJade C staining in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. Behavior was assessed separately using a series of object recognition tasks and a test of social memory beginning at P38. We found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. Behavioral outcome was also equivalent in simple novel object recognition. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact. The profound behavioral impairment in males relative to females, in spite of comparable cell death, suggests that males are more susceptible to long-term cognitive effects and this outcome may not be exclusively attributed to neuronal death.