Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats

Autor: Kavel Visrodia, Vinuta Rau, Jeffrey W. Sall, Laura D. V. May, Michael T. Lee, Greg Stratmann, Ban Ku, Joseph S. Bell, Ran Dai, Rehan S. Alvi, Kathy R. Magnusson
Rok vydání: 2009
Předmět:
Zdroj: Anesthesiology. 110(4)
ISSN: 1528-1175
Popis: Background: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between thesefindings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis. Methods: The S-phase marker 5-bromodeoxyuridine was administered at various times before, during, and afte r4ho f isoflurane given to postnatal day (P)60 and P7 rats to assess dentate gyrus progenitor proliferation, early neuronal lineage selection, and long-term survival of new granule cell neurons. Fear conditioning and spatial reference memory was tested at various intervals from 2 weeks until 8 months after anesthesia. Results: In P60 rats, isoflurane increased early neuronal differentiation as assessed by BrdU/NeuroD costaining, decreased progenitor proliferation for 1 day, and subsequently increased progenitor proliferation 5‐10 days after anesthesia. In P7 rats, isoflurane did not induce neuronal lineage selection but decreased progenitor proliferation until at least 5 days after anesthesia. Isoflurane improved spatial reference memory of P60 rats long-term, but it caused a delayed-onset, progressive, persistent hippocampal deficit in P7 rats in fear conditioning and spatial reference memory tasks. Conclusion: The authors conclude that isoflurane differentially affects both neurogenesis and long-term neurocognitive function in P60 and P7 rats. Neurogenesis might mediate the long-term neurocognitive outcome after isoflurane at different ages.
Databáze: OpenAIRE