Leptin is an adipocytokine that is primarily secreted by white adipose tissue, and it contributes to the pathogenesis of neuropathic pain in collaboration with N-methyl-D-aspartate receptors (NMDARs). Functional NMDARs are a heteromeric complex that primarily comprise two NR1 subunits and two NR2 subunits. NR2A is preferentially located at synaptic sites, and NR2B is enriched at extrasynaptic sites. The roles of synaptic and extrasynaptic NMDARs in the contribution of leptin to neuropathic pain are not clear. The present study examined whether the important role of leptin in neuropathic pain was related to synaptic or extrasynaptic NMDARs. We used a rat model of spared nerve injury (SNI) and demonstrated that the intrathecal administration of the NR2A-selective antagonist NVP-AAM077 and the NR2B-selective antagonist Ro25-6981 prevented and reversed mechanical allodynia following SNI. Administration of exogenous leptin mimicked SNI-induced behavioral allodynia, which was also prevented by NVP-AAM077 and Ro25-6981. Mechanistic studies showed that leptin enhanced NR2B- but not NR2A-mediated currents in spinal lamina II neurons of naïve rats. Leptin also upregulated the expression of NR2B, which was blocked by the NR2B-selective antagonist Ro25-6981, in cultured dorsal root ganglion (DRG) neurons. Leptin enhanced neuronal nitric oxide synthase (nNOS) expression, which was also blocked by Ro25-6981, in cultured DRG cells. However, leptin did not change NR2A expression, and the NR2A-selective antagonist NVP-AAM077 had no effect on leptin-enhanced nNOS expression. Our data suggest an important cellular link between the spinal effects of leptin and the extrasynaptic NMDAR-nNOS-mediated cellular mechanism of neuropathic pain.

Objective. To determine whether bile acids (BAs) affect respiratory functions through the farnesoid X receptor (FXR) expressed in the lungs and to explore the possible mechanisms of BAs-induced respiratory disorder. Methods. Primary cultured alveolar epithelial type II cells (AECIIs) of rat were treated with different concentrations of chenodeoxycholic acid (CDCA) in the presence or absence of FXR inhibitor Z-guggulsterone (GS). Then, expression of FXR in nuclei of AECIIs was assessed by immunofluorescence microscopy. And ultrastructural changes of the cells were observed under transmission electron microscope and analyzed by Image-Pro Plus software. Results. Morphologic damage of AECIIs was exhibited in high BAs group in vitro, with high-level expression of FXR, while FXR inhibitor GS could attenuate the cytotoxicity of BAs to AECIIs. Conclusions. FXR expression was related to the morphologic damage of AECIIs induced by BAs, thus influencing respiratory functions.

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Background: Deep brain stimulation (DBS) is an effective surgical treatment for essential tremor (ET), with the ventral intermediate nucleus (Vim) and posterior subthalamic area (PSA) as the most common targets. The stimulation efficacy of ET with Vim–PSA double-target DBS has been reported. Herein, we aim to propose surgical techniques for Vim–PSA double-target DBS surgery. Methods: This study enrolled six patients with ET who underwent Vim–PSA double-target electrode implantation from October 2019 to May 2022. The targets were located and adjusted using coordinates and multimodality MRI images. A burr hole was accurately drilled in line with the electrode trajectory under the guidance of a stereotactic frame. Novel approaches were adopted during the electrode implantation process for pneumocephalus reduction, including “arachnoid piamater welding” and “water sealing”. Electrophysiological recording was used to identify the implantation sites of the electrodes. A 3D reconstruction model of electrodes and nuclei was established to facilitate programming. Results: The combination of coordinates and multimodality MRI images for target location and adjustment enabled the alignment of Vim and PSA. Postoperative CT scanning showed that the electrode was precisely implanted. Stereotactic guidance facilitated accurate burr hole drilling. “Arachnoid piamater welding” and “water sealing” were efficient in reducing pneumocephalus. Intraoperative electrophysiological verified the efficacy of Vim–PSA double-target DBS surgery. Conclusions: The methods for target location and adjustment, accurate drilling of the burr hole, reduction in pneumocephalus, and intraoperative electrophysiological verification are key issues in DBS surgery targeting both the Vim and PSA. This study may provide technical support for Vim–PSA DBS, especially for surgeons with less experience in functional neurosurgery.