BACKGROUND: Anesthetic agents (eg, isoflurane, propofol) may cause neurodegeneration in the developing brains and impair animals' learning ability. Dexmedetomidine (DEX), a selective alpha 2-adrenoreceptor agonist, has antiapoptotic properties in several brain injury models. Here, we tested whether DEX can protect the brain from neurodegeneration in rats exposed to propofol in utero. MATERIALS AND METHODS: Fetal rats of embryonic day 20 were exposed in utero for 1 hour to propofol anesthesia with DEX or saline, or no anesthesia (control). The fetal brains were harvested 6 hours later. Cleaved caspase-3 levels and the relative number of ionized calcium-binding adaptor molecule 1 (IBA1)-positive cells were assessed by Western blot and immunohistochemistry. Learning and memory functions of the offspring in a separate cohort were assessed at postnatal day 35 by using an 8-arm radial maze. RESULTS: Propofol anesthesia in pregnant rats augmented caspase-3 activation by 217% in the brain tissues of fetal rats and increased the number of IBA1-positive cells in the cortex by 40% and in the thalamus by 270%. Juvenile rats exposed prenatally to propofol were not different than controls on spontaneous locomotor activity, but made more errors of omission and took longer to complete visiting all 8 arms on days 1, 2, and 3 across a 5-day test in the radial arm maze. This neurocognitive deficit was prevented by administration of DEX (5.0 µg/kg, IP), which also significantly inhibited propofol-induced caspase-3 activation and microglial response in the fetal brains. CONCLUSIONS: DEX attenuates neuronal injury induced by maternal propofol anesthesia in the fetal brains, providing neurocognitive protection in the offspring rats.
BACKGROUND: Anesthetic agents (eg, isoflurane, propofol) may cause neurodegeneration in the developing brains and impair animals' learning ability. Dexmedetomidine (DEX), a selective alpha 2-adrenoreceptor agonist, has antiapoptotic properties in several brain injury models. Here, we tested whether DEX can protect the brain from neurodegeneration in rats exposed to propofol in utero. MATERIALS AND METHODS: Fetal rats of embryonic day 20 were exposed in utero for 1 hour to propofol anesthesia with DEX or saline, or no anesthesia (control). The fetal brains were harvested 6 hours later. Cleaved caspase-3 levels and the relative number of ionizedcalcium-binding adaptor molecule 1 (IBA1)-positive cells were assessed by Western blot and immunohistochemistry. Learning and memory functions of the offspring in a separate cohort were assessed at postnatal day 35 by using an 8-arm radial maze. RESULTS:Propofol anesthesia in pregnant rats augmented caspase-3 activation by 217% in the brain tissues of fetal rats and increased the number of IBA1-positive cells in the cortex by 40% and in the thalamus by 270%. Juvenile rats exposed prenatally to propofol were not different than controls on spontaneous locomotor activity, but made more errors of omission and took longer to complete visiting all 8 arms on days 1, 2, and 3 across a 5-day test in the radial arm maze. This neurocognitive deficit was prevented by administration of DEX (5.0 µg/kg, IP), which also significantly inhibited propofol-induced caspase-3 activation and microglial response in the fetal brains. CONCLUSIONS:DEX attenuates neuronal injury induced by maternal propofol anesthesia in the fetal brains, providing neurocognitive protection in the offspring rats.