Abstract
Background:
Anesthesia-induced neurotoxicity may cause permanent dysfunctions in human brains. In this work, we used a cell-based in-vitro model to demonstrate that traditional Chinese medicine, Kami-Shoyo-San may protect ketamine-induced neuronal apoptosis in human embryonic stem cell-differentiated neurons.
Methods:
Human embryonic stem cell-differentiated neurons were cultured in vitro and treated with high-concentration ketamine to induce neuronal apoptosis. Pre-incubation of Kami-Shoyo-San was conducted to evaluate its neuroprotection on ketamine-injured neurons. Quantitative real-time PCR and western blot assays were used to assess brain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B, in response to Kami-Shoyo-San and ketamine treatment. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling pathway was then deactivated, by siRNA application, to further explore its functional role in Kami-Shoyo-San-mediated protection on ketamine-induced apoptosis among human embryonic stem cell-differentiated neurons.
Results:
High concentration of ketamine-induced significant apoptosis, whereas pre-incubation of Kami-Shoyo-San markedly rescued ketamine-induced apoptosis, in human embryonic stem cell-differentiated neurons. Kami-Shoyo-San activated brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling pathway by upregulating brain-derived neurotrophic factor and inducing tropomyosin receptor kinase B phosphorylation. Conversely, siRNA-mediated brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling pathway deactivation reversed the neuroprotection of Kami-Shoyo-San in ketamine-injured human embryonic stem cell-differentiated neurons.
Conclusion:
Kami-Shoyo-San could protect ketamine-induced neurotoxicity, and the underlying mechanism may involve brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling pathway.