Effects of vitamin D on neurotoxicity, neuroinflammation and emotional behaviour in the offspring of mice subjected to sevoflurane anaesthesia during pregnancy

Effects of Vitamin D on Neurotoxicity, Neuroinflammation and Emotional Behaviour in the Offspring of Mice Subjected to Sevoflurane Anaesthesia During Pregnancy Objective: We aimed to investigate the neuroprotective and anti-inflammatory effects of vitamin D on sevoflurane-induced neurotoxicity, neuroinflammation and emotional behavioural changes in offsprings of mice who underwent general anaesthesia during pregnancy. Method: Twenty 8-week-old pregnant Swiss albino mice were divided into four groups with five mice each: control (Group K), vitamin D (Group D), sevoflurane (Group S), and sevoflurane-vitamin D (Group SD). On the 14th day of pregnancy, groups S and SD were exposed to 3% sevoflurane with 6 L/min of 97% O2 for 2 hours. Groups K and D were exposed to 6 L/min of 100% O2 for 2 hours on the same day. Throughout the pregnancy, Group D and Group SD were given vitamin D at a dose of 5mcg/kg, while Groups S and K received 1 milliliter (ml) of saline intraperitoneally (ip). Newborn mice from the groups were included in the study. From each group, twelve mouse pups were taken and, without undergoing behavioral tests on the 7th and 45th days post-birth, tissue sections of the prefrontal cortex and hippocampus were examined by electron microscopy (EM) and immunohistochemical (IH) methods. The IH method assessed the expressions of Interleukin-6 (IL-6), Brain-derived neurotrophic factor (BDNF), Tumor necrosis factor-α (TNF-α), c-Fos, B cell lymphoma/leukemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), and Oligodendrocyte transcription factor 2 (Olig2). Mice not included in the IH and EM experiments from each group were subjected to open field and elevated plus maze tests on the 45th day. Results: Bax, IL-6, TNF- α, c-Fos, Bcl-2, Olig2, BDNF expressions were significantly increased and Bcl-2, Olig2, BDNF expressions were significantly decreased in Group S compared to Group SD in prefrontal and hippocampus tissues. EM images supported these data. No significant difference was found in behavioural tests between the groups. Conclusion: We found that the neuroinflammation and neurotoxicity induced in the offspring of sevoflurane administered to pregnant mice can be reduced by vitamin D. Key words: Sevoflurane, vitamin D, IL-6, BDNF, Bax, TNF- α, c-Fos, Bcl-2, Olig2, EM