Physical activity compensates for isoflurane-induced selective impairment of neuronal progenitor cell proliferation in the young adult hippocampus.

General anesthesia is considered a risk factor for postoperative cognitive dysfunction. However, it is unclear what the neuronal and cognitive consequences of general anesthesia are and whether they can be treated. One possible pathomechanism is hippocampal neurogenesis. We investigated how the anesthetic isoflurane affects adult hippocampal neurogenesis and associated cognitive functions and whether the neurogenic stimulus of physical activity reverses isoflurane-induced changes. We exposed young adult mice to isoflurane (ISO) - half had access to a running wheel (ISO-RW). Both groups were compared with a control condition (CTR; CTR-RW). Cell proliferation and survival in the dentate gyrus of the hippocampus were quantified histologically 48 h and 3 weeks after anesthesia by bromodeoxyuridine incorporation. Cell phenotype was determined by expression of neuronal markers, and the extent of continuous endogenous neuronal proliferation was estimated from the number of doublecortin-positive cells. The Morris water maze was used to test hippocampus-dependent functions. We found that isoflurane decreased proliferation of neuronal progenitor cells, whereas survival of mature neurons remained intact. Consistent with intact neuronal survival, spatial memory associated with neurogenesis also proved intact in the Morris water maze despite isoflurane exposure. Physical activity attenuated the observed neuronal changes by preventing the decrease in newborn neuronal progenitor cells and the decline in continuous endogenous neuronal proliferation in isoflurane-treated animals. In conclusion, isoflurane selectively impairs neuronal proliferation but not survival or neurogenesis-linked cognition in adult mice. The observed adverse effects can be attenuated by physical activity, a cost-effective means of preventing the neurogenic consequences of general anesthesia.

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