PDE-7 Inhibitor BRL-50481 Reduces Neurodegeneration and Long-Term Memory Deficits in Mice Following Sevoflurane Exposure.

Sevoflurane, one of the most commonly used anesthetic agents, has been demonstrated to induce widespread neurodegeneration in the developing brain. We aimed to evaluate the protective effects of a PDE-7 inhibitor (BRL-50481) against the neurotoxic effects of sevoflurane on the developing nervous system. Spatial learning and memory in sevoflurane-treated mice were examined using the Morris water maze test, and neuroprotective effects of PDE-7 inhibitor (BRL-50481) against sevoflurane-induced impairments were evaluated. Our results showed that sevoflurane treatment markedly induced neurodegeneration and impaired long-term memory in neonatal mice. Notably, BRL-50481 coadministration could significantly attenuate sevoflurane-induced learning and memory defects, prevent deterioration of recognition memory, and protect against neuron apoptosis. Mechanistically, BRL-50481 administration suppressed sevoflurane-induced neurodegenerative disorders through restoring cAMP and activating cAMP/CREB signaling in the hippocampus. PDE7 inhibitor may be a potential therapeutic agent for sevoflurane-induced neurodegeneration and long-term memory deficits.