Dexmedetomidine reduced isoflurane neurotoxicity by preventing cytoskeletal depolymerization via the BDNF/RhoA signal pathway

Abstract Background Dexmedetomidine (Dex) has a significant neuroprotective effect in isoflurane-induced neurotoxicity during the critical period of synaptogenesis. However, the mechanisms by which Dex protects developing neurons are not clear. This research evaluated the protective effect of Dex against neuronal damage induced by isoflurane using a mouse model. Methods Neonatal Swiss mice at postnatal day 7 (PND7) were injected intraperitoneally with 15µg/kg, 20µg/kg, or 25µg/kg Dex, or normal saline, and then treated with 2% isoflurane for 2h. The results showed that 20µg/kg Dex could reduce isoflurane-induced neurocognitive deficits as assessed using the Morris water maze. The mechanisms by which Dex protected neurons were investigated using hippocampal neurons isolated from PND4-7 mice and exposed to 2% isoflurane (2h). Dex prevented cytoskeletal depolymerization that was induced by isoflurane. Results 15µg/ml Dex significantly reduced the percentage of apoptotic neurons. Dex reduced expression of activated caspase-3 in neurons compared to isoflurane only exposed mice. Using primary cell cultures from neonatal mouse hippocampi, we determined that dexmedetomidine could reverse isoflurane-induced RhoA (a small