Optimized terahertz generation in BNA organic crystals with chirped Ti:sapphire laser pulses.

We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

Femtosecond Dynamics of Fast Electron Pulses in Relativistic Laser-Foil Interactions.

We report the femtosecond time-resolved dynamics of relativistic electron pulses in ultraintense laser-foil interactions, by characterizing the terahertz self-radiation with single-shot ultrabroadband interferometry. Experimental measurements together with theoretical modeling reveal that the electron pulses inherit the duration of the driving laser pulse. We also visualize the electron recirculation dynamics, where electrons remain trapped inside the self-generated electrostatic potential well and rebound back and forth around the thin foil for hundreds of femtoseconds. Our results not only demonstrate an in situ, real-time metrology scheme for electron bursts, but also have important implications for understanding and manipulating the time-domain properties of laser-driven particle and radiation sources.

Enhanced Postoperative Pain Management and Mobility Following Arthroscopic Knee Surgery: A Comparative Study of Adductor Canal Block with and without IPACK Block.

BACKGROUND Arthroscopic knee surgery (AKS) is minimally invasive, reducing hospital stay compared to traditional surgery, but postoperative pain remains a significant issue. This study compared the analgesic and functional outcomes following AKS following anesthesia using adductor canal block (ACB) with and without anesthesia using the interspace between the popliteal artery and posterior capsule of the knee (IPACK) block under spinal anesthesia (SA). MATERIAL AND METHODS We randomly allocated 120 patients into 3 groups: IPACK+ACB+SA for Group A (n=40), ACB+SA for Group B (n=40), and SA for Group C (n=40). The outcome was the visual analog scale (VAS) score evaluated at rest and during activity at 3 h, 6 h, 12 h, 24 h, and 48 h postoperatively, the frequency of administration of postoperative rescue analgesic, and the maximal walking distance at 24 h and 48 h postoperatively. RESULTS Compared with Group C, the VAS scores in Group A were significantly lower at 48 h postoperatively (P<0.05). There was a significant difference in the frequency of postoperative rescue analgesia use among the 3 groups (P=0.001). In a subgroup analysis of meniscus shaping under arthroscopy, the resting VAS score in Group A was lower than that in Group B and Group C at 48 h postoperatively (P<0.05). The maximum walking distance of Group A was longer than that of Group B and Group C at 24 h and 48 h postoperatively (P<0.01). CONCLUSIONS The effect of postoperative analgesia in the group receiving IPACK combined with ACB after AKS was obviously superior. In arthroscopic meniscus repair surgery, the duration of analgesia was longer, and the maximum walking distance at 48 h postoperatively was longer.

3D power frequency intensive electric field sensor based on a lithium niobate electro-optic crystal.

In order to conveniently measure the power frequency intensive electric field in any direction in space, a lithium niobate (LN) crystal-based three dimensional (3D) intensive electric field sensor with an all-dielectric structure has been developed. A regular triangular prism structure with three 1D (one-dimensional) electric field sensors fixed on its three sides is designed and fabricated. By setting the orientation of the z-axes of the three 1D electric field sensors at 54.7° with respect to the three edges of the prism, the detection directions of the three 1D electric field sensors are perpendicular to each other. Compared to existing 3D electric field sensors that directly arrange three 1D electric field sensors along three mutually perpendicular directions, the overall device volume of the newly designed 3D sensor is significantly reduced. Experimental results reveal that the linear measurement ranges of the 3D electric field sensor along the three axes are 3.71 kV/m-388 kV/m, 2.78 kV/m-403 kV/m, and 4.50 kV/m-375 kV/m, respectively. When the electric field strength is 82.05 kV/m, the measurement error is less than 4.97% when the 3D electric field sensor is rotated 360° in the y o z and x o y planes.

Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual-Signal Transform-Based Selenium Antioxidant.

Spinal cord injury (SCI), following explosive oxidative stress, causes an abrupt and irreversible pathological deterioration of the central nervous system. Thus, preventing secondary injuries caused by reactive oxygen species (ROS), as well as monitoring and assessing the recovery from SCI are critical for the emergency treatment of SCI. Herein, an emergency treatment strategy is developed for SCI based on the selenium (Se) matrix antioxidant system to effectively inhibit oxidative stress-induced damage and simultaneously real-time evaluate the severity of SCI using a reversible dual-photoacoustic signal (680 and 750 nm). Within the emergency treatment and photoacoustic severity assessment (ETPSA) strategy, the designed Se loaded boron dipyrromethene dye with a double hydroxyl group (Se@BDP-DOH) is simultaneously used as a sensitive reporter group and an excellent antioxidant for effectively eliminating explosive oxidative stress. Se@BDP-DOH is found to promote the recovery of both spinal cord tissue and locomotor function in mice with SCI. Furthermore, ETPSA strategy synergistically enhanced ROS consumption via the caveolin 1 (Cav 1)-related pathways, as confirmed upon treatment with Cav 1 siRNA. Therefore, the ETPSA strategy is a potential tool for improving emergency treatment and photoacoustic assessment of SCI.

The Role of Klotho Protein Against Sevoflurane-Induced Neuronal Injury.

The effects of general anesthetics on the developing brain have aroused much attention in recent years. Sevoflurane, a commonly used inhalation anesthetic especially in pediatric anesthesia, can induce developmental neurotoxicity. In this study, the differentially expressed mRNAs in the hippocampus of newborn rats exposed to 3% sevoflurane for 6 h were detected by RNA-Sequencing. Those data indicated that the mRNA of Klotho was increased after exposure to sevoflurane. Moreover, the protein expression of Klotho was assayed by Western Blot. Besides over-expression and under-expression of Klotho protein, we also detected changes of cell proliferation, ROS, JC-1, and Bcl-2/Bax ratio in PC12 cells exposed to sevoflurane. After exposure to 3% sevoflurane, the expression of Klotho protein increased in the hippocampus of neonatal rats. In PC12 cells, exposure to sevoflurane could increase cellular ROS level, reduce mitochondrial membrane potential and Bcl-2/Bax ratio. While overexpression of Klotho alleviated the above changes, knockdown of Klotho aggravated the injury of sevoflurane. Klotho protein could reduce oxidative stress and mitochondrial injury induced by sevoflurane in the neuron.

KLF9 regulates PRDX6 expression in hyperglycemia-aggravated bupivacaine neurotoxicity.

BACKGROUND: Neurotoxicity induced by local anesthetics (LAs) is potentially life threatening, especially for patients with underlying diseases like diabetes. The anesthetic bupivacaine (Bup) has been reported to induce neurotoxicity mediated by reactive oxygen species (ROS), which is aggravated by hyperglycemia. Krüppel-like factor 9 (KLF9), an axon growth-suppressing transcription factor, plays a key role in neuronal maturation and promotes oxidative stress. This study was designed to investigate whether and how KLF9 regulates ROS levels related to LA neurotoxicity under hyperglycemic conditions. METHODS: Klf9/GFP ShRNA (LV Sh-Klf9) was used to achieve stable Klf9 knockdown in the SH-SY5Y cell line. KLF9-deficient and normal cells were cultured under normal or high-glucose (HG) culture conditions and then exposed to Bup. Cell viability, intracellular and mitochondrial ROS, and mitochondrial membrane potential (ΔΨm) were detected to examine the role of KLF9. Thereafter, KLF9-deficient and normal cells were pretreated with small-interfering RNA targeting peroxiredoxin 6 (siRNA-Prdx6) to determine if PRDX6 was the target protein in HG-aggravated Bup neurotoxicity. RESULTS: The mRNA and protein levels of KLF9 were increased after Bup and hyperglycemia treatment. In addition, cell survival and mitochondrial function were significantly improved, and ROS production was decreased after Sh-Klf9 treatment compared with Sh-Ctrl. Furthermore, the expression of PRDX6 was suppressed by Bup in hyperglycemic cultures and was upregulated in the Sh-Klf9 group. Moreover, the protection provided by KLF9 deficiency for cell survival, the increase in ROS production in cells and mitochondria, and the disruption of mitochondrial function were abolished by Prdx6 knockdown. CONCLUSIONS: The results of this study demonstrated that hyperglycemia aggravated Bup neurotoxicity by upregulating KLF9 expression, which repressed the antioxidant PRDX6 and led to mitochondrial dysfunction, ROS burst, and cell death. Understanding this mechanism may, thus, offer valuable insights for the prevention and treatment of neurotoxicity induced by LAs, especially in diabetic patients.

Role of mitochondrial Ca2+ uniporter in remifentanil-induced postoperative allodynia.

Opioid-induced hyperalgesia (OIH) and allodynia is a well-known phenomenon and refers to the pain sensitization in patients after prolonged opioid exposure. OIH limits the use of opioids in pain control, but the underlying mechanisms are not fully clear. This study investigated the role of mitochondrial Ca2+ uniporter (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. Using a rat model of OIH, we found that incision- and remifentanil-induced mechanical allodynia were remarkably attenuated by pretreatment with Ru360, a specific MCU antagonist, suggesting a critical role of MCU in both incision- and opioid-induced allodynia. In addition, imaging studies with Rhod-2 (a mitochondrial Ca2+ dye) in spinal tissues demonstrated increased mitochondrial Ca2+ level in response to incision and remifentanil infusion, which was attenuated by Ru360. Western blot and immunohistochemistry showed that pNR [phosphorylated N-methyl-D-aspartate (NMDA) receptor] and pERK (phosphorylated extracellular signal-regulated kinase) are increased during both incision-induced hyperalgesia and remifentanil-induced hyperalgesia, and again the increases in pNR and pERK were remarkably attenuated by Ru360. Together, our data demonstrate that MCU plays a critical role in remifentanil-induced postoperative mechanical allodynia, with NMDA receptor and ERK as possible downstream effectors. Our findings provide novel mechanisms for remifentanil-induced mechanical allodynia and encourage future studies to examine the mitochondrial Ca2+ uniporter as a potential therapeutic target for prevention of OIH.

High Glucose Enhances Isoflurane-Induced Neurotoxicity by Regulating TRPC-Dependent Calcium Influx.

Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca2+). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca2+ influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca2+ influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure. Next, we investigated cytosolic Ca2+ concentrations, TRPC mRNA expression levels and tested the effect of the TRPC channel blocker SKF96365 on cytosolic Ca2+ levels in cells treated with high glucose or/and isoflurane. Finally, we employed knocked down TRPC6 to demonstrate the role of TRPC in high glucose-mediated enhancement of isoflurane-induced neurotoxicity. The results showed that high glucose could enhance isoflurane-induecd toxic damage in primary hippocampal neurons and SH-SY5Y cells. High glucose enhanced the isoflurane-induced increase of cytosolic Ca2+ in SH-SY5Y cells. High glucose elevated TRPC mRNA expression, especially that of TRPC6. SKF96365 and knock down of TRPC6 were able to inhibit the high glucose-induced increase of cytosolic Ca2+ and decrease isoflurane-induced neurotoxicity in SH-SY5Y cells cultured with high glucose. Our findings indicate that high glucose could elevate TRPC expression, thus increasing Ca2+ influx and enhancing isoflurane-induced neurotoxicity.

Advanced glycation end products activate the miRNA/RhoA/ROCK2 pathway in endothelial cells.

OBJECTIVE: AGEs induce endothelial cell dysfunction in HUVECs, resulting in ROS production and triggering apoptosis. This study sought to identify miRNAs involved in AGE-induced endothelial cell injury. METHODS: Microarray analysis to identify miRNAs altered with AGE stimulation was undertaken, and results were confirmed using real-time quantitative polymerase chain reaction. The interaction of miRNAs with the RhoA and ROCK2 genes was confirmed using luciferase assays, and their effects on expression were determined using Western blot analysis. The effects of AGEs and miRNAs on endothelial cell permeability were assessed. RESULTS: AGEs induced ROS production and apoptosis of HUVECs (p < 0.05). AGE-induced miR-200b and miR-200c downregulation led to increased expression of their target genes, RhoA and ROCK, respectively. AGE-induced endothelial cell permeability and F-actin expression were significantly reduced with both miR-200b and miR-200c mimics (p < 0.05). Furthermore, AGE-induced stress fiber formation was reduced in cells treated with miR-200b mimics. CONCLUSION: miR-200b and miR-200c are suppressed in AGE-induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling. Further studies are necessary to evaluate the therapeutic value of targeting miRNAs or their target genes for treatment of vascular diseases.

Imparting superhydrophobicity to biodegradable poly(lactide-co-glycolide) electrospun meshes.

The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA-PGC18) copolymers and their use as biodegradable polymer dopants is reported to enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven meshes. Solutions of PLGA are doped with PLA-PGC18 and electrospun to form meshes with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer composition influence the nonwetting nature of the meshes and alter their mechanical (tensile) properties. Contact angles as high as 160° are obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal foreign body response when implanted in mice. In summary, a general method for constructing biodegradable fibrous meshes with tunable hydrophobicity is described for use in tissue engineering and drug delivery applications.

Challenges of Post-Venipuncture Jugular Venous Thrombosis in Patients with Secondary Hyperparathyroidism: A Case Report.

BACKGROUND Hyperparathyroidism is a common issue in patients on long-term hemodialysis, necessitating parathyroidectomy with deep venipuncture. These patients frequently exhibit a heightened incidence of vascular calcification, complicating deep venipuncture and increasing the risk of associated complications. Therefore, a crucial aspect of preoperative assessment in this population involves identifying vascular calcification, with a preference for ultrasound-guided intraplane puncture. Special care is required to prevent blood vessel injuries and postoperative complications such as deep vein thrombosis. CASE REPORT We present the case of a 66-year-old woman with secondary hyperparathyroidism who encountered challenges during an internal jugular vein puncture, leading to subsequent thrombosis. Initial attempts were hindered by calcification of the internal jugular vein's vascular wall, resulting in stratified damage to the vessel's wall. However, the ultrasound-guided in-plane puncture technique successfully allowed the insertion of a central venous catheter without further damage to the vascular wall. On the postoperative fourth day, thrombus formation was observed in the damaged vascular wall from the initial puncture. CONCLUSIONS The ultrasound-guided in-plane puncture technique is advantageous in overcoming the difficulties associated with puncturing through deep vein calcification in patients with secondary hyperparathyroidism. This technique also diminishes the likelihood of complications such as venous thrombosis.

Intrathecal rapamycin attenuates the mechanical hyperalgesia of paclitaxel-induced peripheral neuropathy in mice.

Paclitaxel is an extensively used chemotherapy antitumor drug and paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common side effect. Rapamycin, originally used as an adjuvant drug for chemotherapy, has recently been found to possess potential neuroprotective activities. Our purposes of this study are to verify the effect of rapamycin on PIPN, which contributes to a new target for PIPN treatment. Mice were given paclitaxel or rapamycin with different injection methods. Paw withdrawal threshold was tested at different time points for mechanical sensitivity assessment. Administration of paclitaxel, both 2 mg/kg and 5 mg/kg, could induce mechanical hypersensitivity. 0.01 mg intrathecal injection of rapamycin showed the best effect on attenuate the mechanical hyperalgesia of PIPN. Intrathecal injection of only rapamycin would not induce the mechanical hyperalgesia while when rapamycin and paclitaxel were used together the mechanical hyperalgesia induced by paclitaxel could be attenuated. Paclitaxel could induce mechanical hyperalgesia in mice and rapamycin could attenuate such mechanical hyperalgesia of PIPN.

Early monitoring-to-warning Internet of Things system for emerging infectious diseases via networking of light-triggered point-of-care testing devices.

Early monitoring and warning arrangements are effective ways to distinguish infectious agents and control the spread of epidemic diseases. Current testing technologies, which cannot achieve rapid detection in the field, have a risk of slowing down the response time to the disease. In addition, there is still no epidemic surveillance system, implementing prevention and control measures is slow and inefficient. Motivated by these clinical needs, a sample-to-answer genetic diagnosis platform based on light-controlled capillary modified with a photocleavable linker is first developed, which could perform nucleic acid separation and release by light irradiation in less than 30 seconds. Then, on site polymerase chain reaction was performed in a handheld closed-loop convective system. Test reports are available within 20 min. Because this method is portable, rapid, and easy to operate, it has great potential for point-of-care testing. Additionally, through multiple device networking, a real-time artificial intelligence monitoring system for pathogens was developed on a cloud server. Through data reception, analysis, and visualization, the system can send early warning signals for disease control and prevention. Thus, anti-epidemic measures can be implemented effectively, and deploying and running this system can improve the capabilities for the prevention and control of infectious diseases.

A non-collinear autocorrelator for single-shot characterization of ultrabroadband terahertz pulses.

Conventional terahertz (THz) waveform or spectral diagnostics mainly employ the electro-optic-based techniques or the multi-shot Michelson interferometer. Simultaneously, single-shot, ultrabroadband THz spectral measurements remain challenging. In this paper, a novel probe-free scheme based on the non-collinear autocorrelation technique is proposed to characterize the ultrabroadband THz spectrum at a single-shot mode. The non-collinear autocorrelator is a modified beam-division interferometer, in which the two beams are recombined non-collinearly onto a camera. The temporal or spectral resolution and range depend on the noncollinear configuration and camera parameters. This simple approach has been applied experimentally to characterize the ultrashort THz pulse generated from ultraintense laser-solid interactions, demonstrating the capability of single-shot ultrabroadband measurements without an auxiliary ultrafast laser probe. The proposed non-collinear autocorrelator here would be much useful for characterization and applications of low-repetition-rate intense THz sources and could also be extended to other frequency bands.

Highly efficient generation of GV/m-level terahertz pulses from intense femtosecond laser-foil interactions.

The terahertz radiation from ultraintense laser-produced plasmas has aroused increasing attention recently as a promising approach toward strong terahertz sources. Here, we present the highly efficient production of millijoule-level terahertz pulses, from the rear side of a metal foil irradiated by a 10-TW femtosecond laser pulse. By characterizing the terahertz and electron emission in combination with particle-in-cell simulations, the physical reasons behind the efficient terahertz generation are discussed. The resulting focused terahertz electric field strength reaches over 2 GV/m, which is justified by experiments on terahertz strong-field-driven nonlinearity in semiconductors.

Two-dimensional monitoring of a laser-solid x-ray source spot via penumbral coded aperture imaging technique.

The uncertainties of spot size and position need to be clarified for x-ray sources as they can affect the detecting precision of the x-ray probe beam in applications such as radiography. In particular, for laser-driven x-ray sources, they would be more significant as they influence the inevitable fluctuation of the driving laser pulses. Here, we have employed the penumberal coded aperture imaging technique to diagnose the two-dimensional spatial distribution of an x-ray emission source spot generated from a Cu solid target irradiated by an intense laser pulse. Taking advantage of the high detection efficiency and high spatial resolution of this technique, the x-ray source spot is characterized with a relative error of ∼5% in the full width at half maximum of the intensity profile in a single-shot mode for general laser parameters, which makes it possible to reveal the information of the unfixed spot size and position precisely. Our results show the necessity and feasibility of monitoring the spot of these novel laser-driven x-ray sources via the penumbral coded aperture imaging technique.

Ultrasound-Guided Unilateral Transversus Abdominis Plane Combined with Rectus Sheath Block versus Subarachnoid Anesthesia in Patients Undergoing Peritoneal Dialysis Catheter Surgery: A Randomized Prospective Controlled Trial.

BACKGROUND: Peritoneal dialysis catheter placement can be performed under general anesthesia, local anesthesia or subarachnoid anesthesia (SA). Recently, studies have reported the successful placement of peritoneal dialysis catheters using a transversus abdominis plane (TAP) block and rectus sheath (RS) block. This study compared the TAP + RS block with SA for patients undergoing peritoneal dialysis catheter placement. METHODS: Sixty patients were randomly divided into two groups, with 30 receiving unilateral ultrasound-guided TAP + RS block anesthesia and 30 receiving SA. The demographic characteristics, anesthesia efficacy, indicators related to anesthesia or operation, hemodynamic index, postoperative pain numeric rating score (NRS), postoperative recovery indicators, complications related to anesthesia or surgery, and dosage of sedative or analgesic medication were analyzed. RESULTS: Anesthesia operation time was significantly shorter in the TAP + RS block group than in the SA group (P<0.001), while there was no significant difference in success rates (TAP + RS 93.33% [95% confidence interval, 95% CI, 83.9-102.8%] vs SA 100.00% [95% CI, 100-100%], P=0.472). Two patients in the TAP + RS group needed extra analgesia, although the dermatome pinprick sensation test gave negative results for all patients. Patients who received the TAP + RS block expressed significantly less pain on movement or at rest at 4 h and 8 h postoperative. Fewer patients needed rescue analgesia with tramadol in the postoperative period in the TAP + RS block group than in the SA group (P<0.05). The intraoperative MAP was more stable (P<0.05) in the TAP + RS group compared to the SA group. CONCLUSION: The TAP + RS block is a safe, effective method for use as the principal anesthesia technique in PD catheter placement. Compared to SA, it has the advantages of less influence on hemodynamics and a better postoperative analgesic effect.

Inhibition of Ku70 in a high-glucose environment aggravates bupivacaine-induced dorsal root ganglion neurotoxicity.

BACKGROUND: Bupivacaine (BP) is commonly used as a local anaesthetic(LA) in the clinic, but it can also cause neurotoxicity, especially in patients with diabetes. Previous studies have found that high-glucose environments can aggravate BP-induced DNA damage in nerve cells. Ku70 is subunit of the DNA damage repair enzyme DNA-PK. This study was designed to determine whether high-glucose conditions enhance BP neurotoxicity and DNA damage by inhibiting Ku70 expression. METHODS: We examined the effect of BP on apoptosis and DNA damage in murine dorsal root ganglion (DRG) neurons under hyperglycaemic conditions. Untreated DRG cells and DRG cells pretreated with NU7441, a DNA-PK inhibitor, were cultured for 3 days under normal culture conditions or with 50 mM glucose, and the cells were then treated with BP for 3 h. DNA damage was investigated via comet assays, the ratio of early to late apoptotic cells was assessed by Annexin V-FITC/PI staining, and cell viability was measured by CCK-8 assays. The protein expression levels of DNA-PK, Ku70, Bax, Bcl-2 and γH2ax were measured by immunofluorescence or Western blotting. RESULTS: Compared to its effect under normal culture conditions, BP treatment led to decreased cell viability and increased DNA damage in DRG cells grown under high-glucose conditions. The rate of DRG cell apoptosis and the expression of γH2ax, the ratio of Bax to Bcl-2 also increased under the high-glucose conditions. Furthermore, Ku70 expression was inhibited. The DNA-PK inhibitor, NU7441, could significantly inhibit DNA-PK and Ku70 expression, simultaneously further aggravating BP-induced apoptosis and DNA damage under high-glucose conditions. CONCLUSION: These data indicate that hyperglycaemia may enhance BP-induced neurotoxicity and DNA damage by inhibiting the DNA repair protein Ku70.

High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells.

Bupivacaine, a typical local anesthetic, induces neurotoxicity via reactive oxygen species regulation of apoptosis. High glucose could enhance bupivacaine-induced neurotoxicity through regulating oxidative stress, but the mechanism of it is not clear. Mitochondrial calcium uniporter (MCU), a key channel for regulating the mitochondrial Ca2+ (mCa2+) influx, is closely related to oxidative stress via disruption of mCa2+ homeostasis. Whether MCU is involved in high glucose-sensitized bupivacaine-induced neurotoxicity remains unknown. In this study, human neuroblastoma (SH-SY5Y) cells were cultured with high glucose and/or bupivacaine, and the data showed that high glucose enhanced bupivacaine-induced MCU expression elevation, mCa2+ accumulation, and oxidative damage. Next, Ru360, an inhibitor of MCU, was employed to pretreated SH-SY5Y cells, and the results showed that it could decrease high glucose and bupivacaine-induced mCa2+ accumulation, oxidative stress, and apoptosis. Further, with the knockdown of MCU with a specific small interfering RNA (siRNA) in SH-SY5Y cells, we found that it also could inhibit high glucose and bupivacaine-induced mCa2+ accumulation, oxidative stress, and apoptosis. We propose that downregulation expression or activity inhibition of the MCU channel might be useful for restoring the mitochondrial function and combating high glucose and bupivacaine-induced neurotoxicity. In conclusion, our study demonstrated the crucial role of MCU in high glucose-mediated enhancement of bupivacaine-induced neurotoxicity, suggesting the possible use of this channel as a target for curing bupivacaine-induced neurotoxicity in diabetic patients.