Sevoflurane causes cognitive impairment by inducing iron deficiency and inhibiting the proliferation of neural precursor cells in infant mice.

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h. We used the Morris water maze (MWM) to test the cognitive function of infant mice. The proliferation of NPCs was measured using bromodeoxyuridine (BrdU) label and their markers Ki67 and Pax6 in infant brain tissues 12 h after anesthesia. Meanwhile, we used immunohistochemical stain, immunofluorescence assay, western blot, and flow cytometer to evaluate the myelinogenesis, iron levels, and cell proliferation in cortex and hippocampus or in NE4C cells. RESULTS: The results showed that Sev significantly caused cognitive deficiency in infant mice. Further, we found that Sev inhibited oligodendrocytes proliferation and myelinogenesis by decreasing MBP and CC-1 expression and iron levels. Meanwhile, Sev also induced the iron deficiency in neurons and NSCs by downregulating FtH and FtL expression and upregulating the TfR1 expression in the cortex and hippocampus, which dramatically suppressed the proliferation of NSCs and NPCs as indicated by decreasing the colocalization of Pax6+ and BrdU+ cells, and caused the decrease in the number of neurons. Interestingly, iron supplementation before anesthesia significantly improved iron deficiency in cortex and hippocampus and cognitive deficiency induced by Sev in infant mice. Iron therapy inhibited the decrease of MBP expression, iron levels in neurons and oligodendrocytes, and DNA synthesis of Pax6+ cells in hippocampus induced by Sev. Meanwhile, the number of neurons was partially recovered in hippocampus. CONCLUSION: The results from the present study demonstrated that Sev-induced iron deficiency might be a new mechanism of cognitive impairment caused by inhaled anesthetics in infant mice. Iron supplementation before anesthesia is an effective strategy to prevent cognitive impairment caused by Sev in infants.

Sevoflurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis.

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

[Clinical research of vasospasm and vagus reflex during radial artery puncture treated with auricular point sticking].

OBJECTIVE: To evaluate the effect and clinical value of auricular point sticking for the diagnosis and treatment of vasospasm and vagus reflex during radial artery puncture, including radial artery spasm (RAS) and coronary artery spasm (CAS). METHODS: A total of 480 patients were randomized into an observation group (224 cases) and a control group (256 cases). Percutaneous coronary intervention and usual care in perioperative period were used in the control group. Auricular point sticking was began to apply 12 h before percutaneous coronary intervention in the observation group at Jiaogan (AH6a), Shenmen (TF4), Pizhixia (AT4), Neifenmi (CO18), Xin (CO15), Shen (CO10), Shenshangxian (TG2p), 1 min a time every point, once every 2 h, 12 h before and after operation. The incidences of vasospasm and vagus reflex during piercing process were compared, and the usage ratios of vasoactive agent were recorded, including glyceryl trinitrate, dopamine and atropine injections. RESULTS: The incidence of angiospasm was 4.9% (11/224) in the observation group, which was lower than 13.3% (34/256) in the control group (P<0.01). The incidence of vagal reflex of the observation group was 7.1% (16/224), which was lower than 19.5% (50/256) of the control group (P<0.01). The usage ratios of glyceryl trinitrate, atropine and dopamine injections were 3.6% (8/224), 7.1% (16/224), 6.3% (14/224) respectively in the observation group, which were lower than 14.8% (38/256), 15.6% (40/256), 15.2% (39/256) in the control group (all P<0.01). . CONCLUSION: Auricular point sticking achieves effect for the diagnosis and treatment of vasospasm and vagus reflex during radial artery puncture.