ABSTRACT
Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.
Subject(s)
Fear/physiology , Memory/physiology , Neurons/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Brain/physiology , Dentate Gyrus/physiology , Interneurons/physiology , Male , Mice , Mice, Inbred C57BL , Neurons/physiology , Proto-Oncogene Proteins c-fos/metabolismABSTRACT
We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.
Subject(s)
Optical Fibers , Optogenetics , Mice , Animals , Hydrogels , Motor Activity , Sciatic Nerve/physiology , LocomotionABSTRACT
BACKGROUND: As Traditional Chinese Medicine (TCM) drugs, Huangqi and Danshen are always applied in combination for spinal cord injury (SCI) treatment based on the compatibility theory of TCM. Astragalus Polysaccharidesis (APS) and Tanshinone IIA (TSIIA) are the main active ingredients of Huangqi and Danshen, and they both possess neuroprotective effects through antioxidant activities. However, low solubility and poor bioavailability have greatly limited their application. In recent years, selenium nanoparticles (SeNPs) have drawn enormous attention as potential delivery carrier for antioxidant drugs. RESULTS: In this study, TCM active ingredients-based SeNPs surface decorated with APS and loaded with TSIIA (TSIIA@SeNPs-APS) were successfully synthesized under the guidance of the compatibility theory of TCM. Such design improved the bioavailability of APS and TSIIA with the benefits of high stability, efficient delivery and highly therapeutic efficacy for SCI treatment illustrated by an improvement of the antioxidant protective effects of APS and TSIIA. The in vivo experiments indicated that TSIIA@SeNPs-APS displayed high efficiency of cellular uptake and long retention time in PC12 cells. Furthermore, TSIIA@SeNPs-APS had a satisfactory protective effect against oxidative stress-induced cytotoxicity in PC12 cells by inhibiting excessive reactive oxygen species (ROS) production, so as to alleviate mitochondrial dysfunction to reduce cell apoptosis and S phase cell cycle arrest, and finally promote cell survival. The in vivo experiments indicated that TSIIA@SeNPs-APS can protect spinal cord neurons of SCI rats by enhancing GSH-Px activity and decreasing MDA content, which was possibly via the metabolism of TSIIA@SeNPs-APS to SeCys2 and regulating antioxidant selenoproteins to resist oxidative stress-induced damage. CONCLUSIONS: TSIIA@SeNPs-APS exhibited promising therapeutic effects in the anti-oxidation therapy of SCI, which paved the way for developing the synergistic effect of TCM active ingredients by nanotechnology to improve the efficacy as well as establishing novel treatments for oxidative stress-related diseases associated with Se metabolism and selenoproteins regulation.
Subject(s)
Nanoparticles , Selenium , Spinal Cord Injuries , Animals , Antioxidants , Medicine, Chinese Traditional , Rats , Selenium/pharmacology , Selenoproteins , Spinal Cord Injuries/drug therapyABSTRACT
Magnetic nanoparticles have garnered sustained research interest for their promise in biomedical applications including diagnostic imaging, triggered drug release, cancer hyperthermia, and neural stimulation. Many of these applications make use of heat dissipation by ferrite nanoparticles under alternating magnetic fields, with these fields acting as an externally administered stimulus that is either present or absent, toggling heat dissipation on and off. Here, we motivate and demonstrate an extension of this concept, magnetothermal multiplexing, in which exposure to alternating magnetic fields of differing amplitude and frequency can result in selective and independent heating of magnetic nanoparticle ensembles. The differing magnetic coercivity of these particles, empirically characterized by a custom high amplitude alternating current magnetometer, informs the systematic selection of a multiplexed material system. This work culminates in a demonstration of magnetothermal multiplexing for selective remote control of cellular signaling in vitro.
ABSTRACT
OBJECTIVE: Pelvic incidence minus lumbar lordosis mismatch (PI-LL) is directly related to poor quality of life in adult degenerative scoliosis (ADS) patients. The purpose of the study was to determine the most appropriate postoperative PI-LL value for patients with ADS. METHODS: The medical records of patients with ADS in our department were retrospectively collected. The data included age, sex, body mass index, age-adjusted Charlson comorbidity index, osteopenia, length of hospital stay, operative duration, estimated blood loss, American Society of Anaesthesiologists score, number of fusion levels, lumbar lordosis, sagittal vertical axis, pelvic incidence, PI-LL, SRS-22 score, ODI score, and mechanical complications. RESULTS: A total of 316 patients were enrolled. PI-LL, lumbar lordosis, sagittal vertical axis, SRS-22 score, ODI score at the time of last follow-up were 20.7±8.5°, 23.4±14.1°, 4.0±2.1 cm, 3.7±0.9, and 18.1±5.5, respectively. In terms of mechanical complications, 88 patients (27.8%), 34 patients (10.8%), and 19 patients (6.0%) had proximal junctional kyphosis, distal junctional kyphosis, and implant-related complications, respectively. In the fully adjusted model, compared with 0 grade PI-LL group and ++ grade PI-LL group, + grade PI-LL group had the best clinical outcomes and the fewest mechanical complications. The stability of these conclusions was verified in sensitivity analyses. CONCLUSIONS: Optimal PI-LL value should be 10°-20° after corrective surgery in patients with adult degenerative scoliosis, which is associated with excellent clinical outcomes and lower complication rates. Previous criteria may be at risk of overcorrection, which may lead to proximal junctional kyphosis.
ABSTRACT
Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable "viscobeads" technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.
ABSTRACT
Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.
Subject(s)
Hydrogels , Mice, Transgenic , Optogenetics , Polymers , Polyvinyl Alcohol , Animals , Polyvinyl Alcohol/chemistry , Mice , Hydrogels/chemistry , Optogenetics/methods , Polymers/chemistry , Nanotubes, Carbon/chemistry , Ventral Tegmental Area/physiology , Microelectrodes , Male , Channelrhodopsins/metabolism , Channelrhodopsins/chemistry , Channelrhodopsins/geneticsABSTRACT
The biohybrid sensor is an emerging technique for multi-functional detection that utilizes the instinctive responses or interactions of biomolecules. We develop a biohybrid pH sensor by taking advantage of the pH-dependent photoelectric characteristics of proteorhodopsin (pR). The transient absorption kinetics study indicates that the photoelectric behavior of pR is attributed to the varying lifetime of the M intermediate at different environmental pH values. This pR-based biohybrid light-powering sensor with microfluidic design can achieve real-time pH detection with quick response and high sensitivity. The results of this work would shed light on pR and its potential applications.
Subject(s)
Rhodopsin/chemistry , Electrodes , Hydrogen-Ion Concentration , Kinetics , Light , Microfluidic Analytical Techniques , Phosphatidylcholines/chemistry , Rhodopsins, Microbial , Tin Compounds/chemistryABSTRACT
Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality. In this study, we utilized an atomic layer deposition (ALD) technique to generate an inorganic, silicon dioxide (SiO2) coating layer on chemically cross-linked PVA hydrogel fibers. To evaluate the stability of SiO2-coated PVA hydrogel fibers mimicking the in vivo environment, we conducted accelerated stability tests. SiO2-coated PVA hydrogel fibers showed improved stability over a one-week incubation period under a harsh environment, preventing swelling and preserving their mechanical and optical properties compared to uncoated fibers. These SiO2-coated PVA hydrogel fibers demonstrated nanoscale polymeric crystalline domains (6.5 ± 0.1 nm), an elastic modulus of 73.7 ± 31.7 MPa, a maximum elongation of 113.6 ± 24.2%, and minimal light transmission loss (1.9 ± 0.2 dB cm-1). Lastly, we applied these SiO2-coated PVA hydrogel fibers in vivo to optically activate the motor cortex of transgenic Thy1::ChR2 mice during locomotor behavioral tests. This mouse cohort was genetically modified to express the light-sensitive ion channel, channelrhodopsin-2 (ChR2), and implanted with hydrogel fibers to deliver light to the motor cortex area (M2). Light stimulation via hydrogel fibers resulted in optogenetically modulated mouse locomotor behaviors, including increased contralateral rotation, mobility speeds, and travel distances.
Subject(s)
Hydrogels , Silicon Dioxide , Animals , Mice , Hydrogels/chemistry , Polyvinyl Alcohol/chemistry , Prostheses and Implants , Water/chemistryABSTRACT
Bioelectronic devices made of soft elastic materials exhibit motion-adaptive properties suitable for brain-machine interfaces and for investigating complex neural circuits. While two-dimensional microfabrication strategies enable miniaturizing devices to access delicate nerve structures, creating 3D architecture for expansive implementation requires more accessible and scalable manufacturing approaches. Here we present a fabrication strategy through the control of metamorphic polymers' amorphous-crystalline transition (COMPACT), for hydrogel bioelectronics with miniaturized fiber shape and multifunctional interrogation of neural circuits. By introducing multiple cross-linkers, acidification treatment, and oriented polymeric crystalline growth under deformation, we observed about an 80% diameter decrease in chemically cross-linked polyvinyl alcohol (PVA) hydrogel fibers, stably maintained in a fully hydrated state. We revealed that the addition of cross-linkers and acidification facilitated the oriented polymetric crystalline growth under mechanical stretching, which contributed to the desired hydrogel fiber diameter decrease. Our approach enabled the control of hydrogels' properties, including refractive index (RI 1.37-1.40 at 480 nm), light transmission (> 96%), stretchability (95% - 111%), and elastic modulus (10-63 MPa). To exploit these properties, we fabricated step-index hydrogel optical probes with contrasting RIs and applied them in optogenetics and photometric recordings in the mouse brain region of the ventral tegmental area (VTA) with concurrent social behavioral assessment. To extend COMPACT hydrogel multifunctional scaffolds to assimilate conductive nanomaterials and integrate multiple components of optical waveguide and electrodes, we developed carbon nanotubes (CNTs)-PVA hydrogel microelectrodes for hindlimb muscle electromyographic and brain electrophysiological recordings of light-triggered neural activities in transgenic mice expressing Channelrhodopsin-2 (ChR2).
ABSTRACT
Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.
Subject(s)
Glaucoma , Retinal Ganglion Cells , Mice , Animals , Retinal Ganglion Cells/pathology , Retinal Ganglion Cells/physiology , Electroretinography/methods , Optogenetics , Glaucoma/pathology , LightABSTRACT
Due to their unique physicochemical characteristics, 2D materials have attracted more and more attention in the biomedicine field. Currently, 2D materials-based nanomedicines have been extensively applied in various diseases including cancer, bacterial infection, tissue engineering, biological protection, neurodegenerative diseases, and cardiovascular disease. Depending on their various characteristics, these 2D nanomedicines exert their therapeutic effect in different ways, showing great clinical application prospects. Herein, we focus on the various biomedical applications of 2D materials-based nanomedicine. The structures and characteristics of several typical 2D nanomaterials with different configurations and their corresponding biomedical applications are first introduced. Then, the potential of 2D nanomedicines on therapeutic and imaging and their biological functionalization are discussed. Furthermore, the therapeutic potentials of 2D nanomedicines in various diseases are also comprehensively summarized. At last, the challenges and perspectives for the advancement of 2D nanomedicines in clinical transformation are outlooks.
Subject(s)
Nanostructures , Neoplasms , Humans , Nanomedicine , Nanostructures/chemistry , Nanostructures/therapeutic use , Neoplasms/drug therapy , Tissue EngineeringABSTRACT
Background: Developmental atlantal stenosis with myelopathy (DASM) in adults is a rare disease that only sporadic cases have been reported over the years. C1 laminectomy (C1L) is one of the most common operations for its treatment. However, as an open surgery, it has shortcomings such as large trauma and slow postoperative rehabilitation, and minimally invasive spine surgery (MISS) offers alternative treatment options with advantages. MISS instruments expand the technical capabilities of surgeons, which allows safer and more effective therapeutics for difficult and complicated diseases. This case report presents a new minimally invasive approach; percutaneous full endoscopic C1 laminectomy (PFEC1L), for the treatment of DASM, and to consolidate the current literature on the condition to summarize its etiologies, clinical manifestations, diagnostic criteria, surgical management, and prognoses. Case Description: The patient in Case 1 presented with neck pain and numbness and weakness in the limbs. The patient in Case 2 presented with numbness in the extremities and the patient in Case 3 presented with bilateral hand numbness and left lower limb weakness. They were all diagnosed with DASM and underwent PFEC1L treatment to maintain the enlargement and decompression of the atlantal canal, which achieved favorable outcomes without complications during the postoperative follow-up visit. Conclusions: DASM is rare but potentially dangerous. Its diagnosis is made based on clinical manifestations combined with radiological imaging examinations, especially computed tomography (CT) scan and magnetic resonance imaging (MRI). While C1L is the most common surgical method, PFEC1L is a new feasible and safe therapeutic option with comparable good outcomes and the advantage of being minimally-invasive. To our knowledge this is the first report that PFEC1L was applied for DASM treatment.
ABSTRACT
BACKGROUND: The aim of the present study was to evaluate the curative effect and safety of thoracic full-endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) for treating ossification of the ligamentum flavum (OLF) with myelopathy. METHODS: Between January 2015 and December 2018, 23 consecutive patients with symptomatic thoracic OLF were treated with TE-ULBD. Of these, 21 (13 women and 8 men, aged 49-75 years) were included in the study and followed up for a minimum of 1 year. The mean blood loss was 15.48 mL (10-30 mL), operative duration was 78.86 min (55-115 min), and hospitalization was 5.05 days (3-15 days). The Japanese Orthopaedic Association (JOA) was used to evaluate spinal cord function, and the curative effect was defined by the JOA improvement rate. The area of OLF (AOLF), the maximum spinal cord compression (MSCC), and the area of spinal cord (ASC) were used to evaluate OLF clearance and spinal cord decompression status. RESULTS: At the final follow up,the JOA score was 8.33 points (5-11 points), which was a significant improvement from the preoperative 5.33 points (3-9 points, P<0.01). The excellent and good rate was 76.19% (16/21). The average preoperative AOLF and AOLF ratio were 85.27±23.66 mm2 and 57.86%±11.86%, respectively, and the postoperative AOLF and AOLF ratio were 16.27±11.75 mm2 and 8.13%±5.38%, respectively. The MSCC increased from 27.99%±13.51% preoperatively to 48.02%±6.66% postoperatively. The ASC was 42.90±10.60 mm2 preoperatively and 64.54±21.36 mm2 postoperatively. There were statistically significant differences in all parameters preoperatively and postoperatively (P<0.01). One case had postoperative hematoma, and the symptoms gradually eased after 3 weeks of conservative treatment. There were no other complications. No recurrence of OLF was detected during the follow-up period. CONCLUSIONS: TE-ULBD is safe and effective for thoracic OLF with the advantages of reduced trauma and bleeding, and faster recovery.
ABSTRACT
BACKGROUND: The aim of the present study was to report a new technique for electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy and to evaluate the efficacy of this technology in the treatment of lumbar disc herniation (LDH). METHODS: This is a retrospective study. Seventeen patients who underwent electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy in our department from September to November 2018 were included in the study. Patients' hospital charts, magnetic resonance imaging results, surgical data and follow-up records were reviewed. Outcomes were assessed by visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and postoperative complications. RESULTS: The median follow-up time was 20.64 months (range, 19-21 months). The average operating time was 52.94±12.88 min (range, 35-78 min), including the working tube introduction time (13.59±2.89 min), decompression time (39.35±13.61 min), and the fluoroscopic time (3.65±2.52 min). Postoperative back VAS, leg VAS, and ODI were significantly improved compared with pre-operation, respectively (P<0.01). The overall excellent and good rate of these seventeen patients was 94%. There were no significant complications related to the operation. CONCLUSIONS: Electromagnetic navigation system-assisted percutaneous full-endoscopic foraminoplasty and discectomy is a safe and effective method for treating LDH and this method has the advantage of short operative time and fluoroscopic times.
Subject(s)
Diskectomy, Percutaneous , Diskectomy , Electromagnetic Phenomena , Humans , Lumbar Vertebrae/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
Understanding the function of nitric oxide, a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule in situ to specific cells. To address this need, we have developed iron sulfide nanoclusters that catalyse nitric oxide generation from benign sodium nitrite in the presence of modest electric fields. Locally generated nitric oxide activates the nitric oxide-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and the latency of TRPV1-mediated Ca2+ responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows nitric oxide-mediated neuronal interrogation in vivo. The in situ generation of nitric oxide in the ventral tegmental area with the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This nitric oxide generation platform may advance mechanistic studies of the role of nitric oxide in the nervous system and other organs.
Subject(s)
Electrochemical Techniques/methods , Electrophysiological Phenomena/physiology , Neurons , Nitric Oxide , Animals , Brain/cytology , Brain/physiology , Calcium/metabolism , HEK293 Cells , Humans , Male , Metal Nanoparticles/chemistry , Mice , Mice, Inbred C57BL , Neurons/metabolism , Neurons/physiology , Nitric Oxide/analysis , Nitric Oxide/metabolism , TRPV Cation Channels/metabolismABSTRACT
BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.
Subject(s)
Decompression, Surgical/methods , Lumbar Vertebrae/surgery , Spinal Stenosis/surgery , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: Cervical stenosis with myelopathy caused by ossification of the ligamentum flavum is relatively rare. Surgical treatment is the preferred option. Previous surgical procedures usually require assisted internal fixation, and some problems may occur, such as large trauma, intraoperative bleeding, wound infection, and internal fixation failure. The aim of this paper is to introduce a new minimally invasive surgical procedure for the treatment of upper cervical spinal stenosis complicated with myelopathy. METHODS: A 56-year-old man with cervical myelopathy (C2-3) caused by calcification of the ligamentum flavum underwent posterior percutaneous full-endoscopic cervical laminectomy and decompression (PECLD) and achieved good clinical efficacy. RESULTS: A surgical incision just 1 cm in size was made, and there was little bleeding during the operation. The patient was hospitalized for 2 days and returned to work after 4 weeks. The patient's postoperative recovery of neurologic function was significantly improved, pain was obviously reduced, and quality of life was remarkably improved. No intra- or postoperative surgical complications were encountered. CONCLUSIONS: PECLD is an effective method for treating cervical stenosis associated with myelopathy because of ossification of the ligamentum flavum. It has the advantages of smaller trauma, less bleeding, shorter postoperative hospital stay, and faster recovery. Taken together, this minimally technique can be considered as a good alternative to traditional open surgery.
ABSTRACT
Spinal cord injury (SCI) remains a challenging clinical problem worldwide, due to the lack of effective drugs for precise treatment. Among the complex pathophysiological events following SCI, reactive oxygen species (ROS) overproduction plays a particularly significant role. As therapeutic agents for neurological diseases, tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) have been widely used in the clinical treatment of SCI. Our previous studies have reported that functionalized selenium nanoparticles (SeNPs) exhibit excellent antioxidant activity against oxidative stress-related diseases. Therefore, in this study, novel multifunctionalized SeNPs decorated with polysaccharide-protein complex (PTW)/PG-6 peptide and loaded with TMP/GM1 were rationally designed and synthesized, which exhibited a satisfactory size distribution and superior stability. Furthermore, the protective effects of SeNPs@GM1/TMP on PC12 cells against tert-butyl hydroperoxide (t-BOOH)-induced cytotoxicity and the underlying mechanisms were also explored. Flow cytometric analysis indicated that SeNPs@GM1/TMP showed strongly protective effects against t-BOOH-induced G2/M phase arrest and apoptosis. Moreover, we found that SeNPs@GM1/TMP could attenuate ROS overproduction to prevent mitochondria dysfunction via inhibiting the activation of p53 and MAPK pathways. Effects of SeNPs@GM1/TMP on functional recovery after SCI were evaluated by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. The results of hematoxylin-eosin staining and Nissl staining also showed that SeNPs@GM1/TMP provided a neuroprotective effect in SCI rats. This finding suggests that SeNPs@GM1/TMP could be further developed as a promising nanomedicine for efficient SCI treatment.
Subject(s)
Antioxidants/administration & dosage , Nanoparticles/administration & dosage , Neuroprotective Agents/administration & dosage , Oxidative Stress/drug effects , Selenium/administration & dosage , Spinal Cord Injuries/drug therapy , Animals , Antioxidants/chemistry , Cell Survival/drug effects , Female , Mitochondria/metabolism , Nanoparticles/chemistry , Neurons/drug effects , Neurons/pathology , Neuroprotective Agents/chemistry , PC12 Cells , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Selenium/chemistry , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathologyABSTRACT
Connecting neural circuit output to behaviour can be facilitated by the precise chemical manipulation of specific cell populations1,2. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways3,4. However, their application to studies of behaviour has thus far been hampered by a trade-off between the low temporal resolution of systemic injection versus the invasiveness of implanted cannulae or infusion pumps2. Here, we developed a remotely controlled chemomagnetic modulation-a nanomaterials-based technique that permits the pharmacological interrogation of targeted neural populations in freely moving subjects. The heat dissipated by magnetic nanoparticles (MNPs) in the presence of alternating magnetic fields (AMFs) triggers small-molecule release from thermally sensitive lipid vesicles with a 20 s latency. Coupled with the chemogenetic activation of engineered receptors, this technique permits the control of specific neurons with temporal and spatial precision. The delivery of chemomagnetic particles to the ventral tegmental area (VTA) allows the remote modulation of motivated behaviour in mice. Furthermore, this chemomagnetic approach activates endogenous circuits by enabling the regulated release of receptor ligands. Applied to an endogenous dopamine receptor D1 (DRD1) agonist in the nucleus accumbens (NAc), a brain area involved in mediating social interactions, chemomagnetic modulation increases sociability in mice. By offering a temporally precise control of specified ligand-receptor interactions in neurons, this approach may facilitate molecular neuroscience studies in behaving organisms.