It has been reported that neonatal isoflurane exposure causes behavioral abnormalities following neurodegeneration in animals and gamma-aminobutyric acid type A (GABA_A) receptor activation during the synaptogenesis is considered to be one possible trigger. Additionally, the inhibitory effect of excitatory GABA_A receptor signaling on the granule cell (GC) migration in the neonatal rat dentate gyrus (DG) was reported in a febrile seizure model. Then, we hypothesized that neonatal isoflurane exposure, which activates GABA_A receptor, causes GC migration disturbances in the neonatal rat. Rat pups were injected with 5-bromo-2’-deoxyuridine (BrdU) and divided into five treatment groups, and double immunofluorescent staining targeting BrdU and homeobox prospero-like protein 1 (Prox1) was performed to examine the localization of BrdU/Prox1 colabeled cells, and then the GC migration was assessed. As a result, we found that the ectopic migration of GC after 2% isoflurane exposure on postnatal day 7 significantly increased after P21. The number of hilar ectopic GCs was influenced by the concentration of isoflurane and the exposure day but not by carbon dioxide exposure. Our main finding is that neonatal isoflurane anesthesia disturbs the migration of GCs in the rat DG, which may be one possible mechanism underlying the neurotoxicity following neonatal isoflurane anesthesia.

The epithelial basal lamina of the small intestine has numerous fenestrations for intraepithelial migration of leukocytes. We have reported dynamic changes of fenestrations in dietary conditions. To investigate this phenomenon, we performed statistical analyses using scanning electron microscopy images of the epithelial basal lamina of rat intestinal villi after removal of the villous epithelium by osmium maceration. We examined structural changes in the number and size of fenestrations in the rat jejunum and ileum under fasted and fed states for 24 h. Our findings revealed that, in the jejunum, the number of free cells migrating into the epithelium through fenestrations increased from 2 h after feeding, resulting in an increase in the fenestration size of intestinal villi; the number of free cells then tended to decrease at 6 h after feeding, and the fenestration size also gradually decreased. By contrast, the increase in the fenestration size by feeding was not statistically significant in the ileum. These findings indicate that the number of migrating cells increases in the upper part of the small intestine under dietary conditions, which may influence the absorption efficiency of nutrients including lipids, as well as the induction of nutrient-induced inflammation.

Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.