Triiodothyronine attenuates neurocognitive dysfunction induced by sevoflurane in the developing brain of neonatal rats.

BACKGROUND: Whilst concerns have been raised about the detrimental effects of general anaesthetics on the brain's development and function in the young, reports have indicated that thyroid hormones are able to promote neurogenesis in the developing brain. This present study aimed to investigate the effects of triiodothyronine (T3) on the neonatal rat brain, following sevoflurane exposure. METHODS: Postnatal day 7 (P7) ratpups were treated with Triiodothyronine (T3) (1 µg/100 g body weight, i.p. injection, once/day for 3 days) after 2% sevoflurane exposure for 6 h. They were sacrificed at either P7 (immediately), P15 or P30 and their brains were harvested to assess cell death, proliferation in the hippocampus, N-methyl-D-aspartate (NMDA) receptor subunit A and B, and a post-synaptic protein (PSD-95 in the hippocampus,). Neuro-behavioral changes in other cohorts between P27 and P30 were evaluated with Morris water maze and open field tests. RESULTS: Sevoflurane exposure caused cell death and suppressed the proliferation of astrocytes and neurons, as well as the dendritic growth of neurons in the hippocampus which were all reversed by the administration of T3. Moreover, cognitive function, including learning, memory, and adaptability to a new environment, were impaired by sevoflurane exposure, which was also negated by T3 treatment. Furthermore, sevoflurane decreased the expression of NMDA receptor subunits NR2A and NR2B, as well as PSD-95 in the hippocampus at P15 and those effects of sevoflurane were abolished by T3 administration. CONCLUSIONS: A potential therapeutic role of T3 in protecting general anesthetic induced neuronal injury in the developing brain is likely to occur through enhancing expression of PSD-95 and the NMDA NR2A and NR2B expression.