No abstract

Subthalamic nucleus deep brain stimulation (STN DBS) ameliorates motor symptoms of Parkinson’s disease, but the precise mechanism is still unknown. Here, using a large animal (pig) model of human STN DBS neurosurgery, we utilized fast-scan cyclic voltammetry in combination with a carbon-fiber microelectrode (CFM) implanted into the striatum to monitor dopamine release evoked by electrical stimulation at a human DBS electrode (Medtronic 3389) that was stereotactically implanted into the STN using MRI and electrophysiological guidance. STN electrical stimulation elicited a stimulus time-locked increase in striatal dopamine release that was both stimulus intensity- and frequency-dependent. Intensity-dependent (1–7 V) increases in evoked dopamine release exhibited a sigmoidal pattern attaining a plateau between 5 to 7 V of stimulation, while frequency-dependent dopamine release exhibited a linear increase from 60 to 120 Hz and attained a plateau thereafter (120–240 Hz). Unlike previous rodent models of STN DBS, optimal dopamine release in the striatum of the pig was obtained with stimulation frequencies that fell well within the therapeutically effective frequency range of human DBS (120–180 Hz). These results highlight the critical importance of utilizing a large animal model that more closely represents implanted DBS electrode configurations and human neuroanatomy to study neurotransmission evoked by STN DBS. Taken together, these results support a dopamine neuronal activation hypothesis suggesting that STN DBS evokes striatal dopamine release by stimulation of nigrostriatal dopaminergic neurons.

A carbon nanofiber (CNF) electrode array was integrated with the Wireless Instantaneous Neurotransmitter Sensor System (WINCS) for detection of dopamine using fast scan cyclic voltammetry (FSCV). Dopamine detection performance by CNF arrays was comparable to that of traditional carbon fiber microelectrodes (CFMs), demonstrating that CNF arrays can be utilized as an alternative carbon electrodes for neurochemical monitoring.

BackgroundMesenchymal stem cell-derived conditioned medium (MSC-CM) has emerged as a promising cell-free tool for restoring degenerative diseases and treating traumatic injuries. The present study describes the effect of selenium as a reactive oxygen species (ROS) scavenger and its additive effect with basic fibroblast growth factor (bFGF) on in vitro expansion of amniotic fluid (AF)-MSCs and the paracrine actions of AF-MSC-CM as well as the associated cellular and molecular mechanisms.MethodsIn this study, we obtained CM from human AF-MSCs cultured with selenium. The stemness of selenium-treated AF-MSCs was evaluated by cell growth and differentiation potential. Human fibroblasts were treated with AF-MSC-CM and analyzed for cell signaling changes. For in vivo wound healing assay, ICR mice with a full-thickness skin wound were used.ResultsSelenium played a critical role in in vitro expansion of AF-MSCs through activation of the AKT-ERK1/2, Smad2, and Stat3 signaling pathways along with inactivation of GSK3β. When administered together with bFGF, it showed remarkable effect in inhibiting ROS accumulation and preserving their multipotency. Proliferation and migration of human dermal fibroblasts and in vivo wound healing were improved in the CMs derived from AF-MSCs exposed to selenium and bFGF, which was caused by the Smad2, AKT-MEK1/2-ERK, and NFκB signaling triggered by the paracrine factors of AF-MSCs, such as TGF-β, VEGF, and IL-6. Our results suggest the following: (a) supplementation of selenium in AF-MSC culture contributes to in vitro expansion and preservation of multipotency, (b) ROS accumulation causes progressive losses in proliferative and differentiation potential, (c) the separate activities of bFGF and selenium in MSCs exert an additive effect when used together, and (d) the additive combination improves the therapeutic effects of AF-MSC-derived CMs on tissue repair and regeneration.ConclusionAntioxidants, such as selenium, should be considered as an essential supplement for eliciting the paracrine effects of MSC-CMs.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1058-z) contains supplementary material, which is available to authorized users.