Abstract

It has been reported that neonatal isoflurane exposure causes behavioral abnormalities following neurodegeneration in animals and gamma-aminobutyric acid type A (GABAA) receptor activation during the synaptogenesis is considered to be one possible trigger. Additionally, the inhibitory effect of excitatory GABAA┬áreceptor 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 GABAA┬áreceptor, 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.

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Uchida, Hashimoto, Saito, Takita, & Morimoto.
Biomedical Research 2022