Neural Tissue Research Articles

Biomimetic Versatile Anisotropic, Electroactive Cellulose Hydrogel Scaffolds Tailored from Fern Stem Serving as Nerve Conduit and Cardiac Patch.

Peripheral nerve injury (PNI) and myocardial infarction (MI) are the two most clinically common soft excitable tissue injuries. Both nerve and cardiac tissues exhibit structural anisotropy and electrophysiological activity, providing a wide range of biophysical cues for cell and tissue repair. However, balancing microstructural anisotropy, electroactivity, and biocompatibility is challenging. To address this issue, Dicranopteris linearis (D. linearis) is proposed as a low-perceived value fern plant. Moreover, to enhance its usefulness, it can be designed into a tubular structure and a lamellar structure to bridge the damaged tissue. Therefore, a robust yet simple top-down approach is proposed to designing and fabricating the desired biomimetic versatile hydrogels orienting from the D. linearis to customize for different soft excitable tissue repair applications. These anisotropic electroactive hydrogels performed well as nerve guidance conduits (NGC) and engineered cardiac patches (ECP) in the repair of PNI and MI, respectively. Two birds, one stone. Accordingly, the biomimetic strategy of D. linearis to NGC and D. linearis to ECP is first proposed, opening a new horizon for constructing tissue engineering using natural sources.

Iodinated contrast dye-diluent combination exhibits longer time to full dye saturation compared to lidocaine, bupivacaine, and water in porcine cadaveric nervous tissue.

Dye-diluent combinations have different nerve-staining behavior, making locoregional cadaveric dye study findings difficult to compare. The objective of this study was to quantify the effect of 4 diluents on nerve color saturation when used in combination with commercial food dye. 48 unpreserved brachial plexus nerves were randomized into 4 diluent groups. Lidocaine, bupivacaine, iodinated contrast, and sterile water were combined with commercial food dye (10:1), and prosected nerves were immersed in one of these groups for 1, 15, 30, or 60 minutes. Images at baseline and at each timepoint were processed using ImageJ. Color saturation was divided into quartiles (dark, medium dark, medium light, or light). The percentage of nerve area stained in each quartile was compared using a 2-way ANOVA and post hoc Tukey test. At 1 minute, water and bupivacaine had a higher percentage of area of dark saturation compared to contrast. At 15 and 30 minutes, dark and medium-dark saturation percentages of area were also larger in lidocaine, bupivacaine, and water compared to contrast. There were no differences in saturation percentages of areas between groups at 60 minutes. Within groups, all diluents had darker percentages of area saturation at 15, 30, and 60 minutes compared to minute 1. In porcine nerves, the staining profiles of 2% lidocaine, 0.5% bupivacaine, and sterile water combined withcommercial food dye appear similar and may be used interchangeably after 15 minutes of exposure. When using iodinated contrast, exposures over 60 minutes yield comparable results to other diluents. Diluents contribute to heterogeneous nerve-staining behavior and should be considered when comparing study outcomes. If contrast is used as the diluent in cadaveric studies with postoperative imaging, researchers should be aware of the significant delay to reach a saturation level comparable to other diluent combinations.

Bone marrow mesenchymal stem cells modulate miR-202-3p to suppress neuronal apoptosis following spinal cord injury through autophagy activation via the AMPK, MAPK, and PI3K/AKT/mTOR signaling pathway

Bone marrow mesenchymal stem cells (BMMSCs) have garnered attention as promising therapeutic modalities for spinal cord injury (SCI) due to their neuroregenerative, anti-apoptotic, and functional recovery-enhancing properties. The central role of microRNAs (miRNAs) in mediating the beneficial outcomes resulting from BMMSCs in SCI has been highlighted in recent studies, suggesting that targeted modulation of specific miRNAs holds potential for augmenting SCI recovery. Our previous investigation implicated miR-202-3p in the reparative processes of injured spinal cords, although the precise mechanistic underpinnings remain elusive. In vivo, BMMSCs were administered to SCI rats, while in vitro, miR-202-3p was transfected into PC-12 cells. Motor capabilities recovery was assessed via Basso-Beattie-Bresnahan (BBB) scores and footprinting tests; the evaluation of neuronal and spinal cord tissue repair was conducted using Nissl staining, TUNEL staining, hematoxylin and eosin (HE) staining, and immunofluorescence; and the impacts of miR-202-3p on cellular autophagy, neuronal apoptosis, and relevant pathways were evaluated using Western blotting, quantitative polymerase chain reaction (qPCR), and transmission electron microscopy (TEM). Functionally, BMMSCs utilized miR-202-3p to improve motor recovery in SCI rats. Histopathologically, they contributed to the repair of damaged spinal cords and the regeneration of nerve axons. At the molecular level, BMMSCs stimulated autophagy and suppressed neuronal apoptosis by regulating the AMPK, MAPK, and PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that BMMSCs coordinate miR-202-3p to inhibit mTOR activation via the AMPK, MAPK, and PI3K/AKT pathways, thereby promoting TFEB dephosphorylation, modulating autophagy and neuronal apoptosis, and ultimately fostering functional recovery post-SCI.

Acid-sensing ion channel-1 contributes to the failure of myelin sheath regeneration following spinal cord injury by transcellular delivery of PGE2

BackgroundTraumatic injuries to spinal cord lead to severe motor, sensory, and autonomic dysfunction. The accumulation of inhibitory compounds plays a pivotal role in the secondary damage to sparing neural tissue and the failure of axonal regeneration and remyelination. Acid-sensing ion channel-1(ASIC1A) is widely activated following neurotrauma, including spinal cord injury (SCI). However, its role in SCI remains elusive.MethodsThe effects of acidic environment on the differentiation and genes changes of neural stem cells (NSCs) were assessed by immunofluorescence staining and RNA-sequencing analysis, respectively. The expression of ASIC1A and prostaglandin endoperoxide synthase 2 (PTGS2) were detected by western blot and immunofluorescence staining. The concentration of prostaglandin E2 (PGE2) within NSC-derived extracellular vesicles were evaluated by ELISA. Small-interfering RNAs (siRNAs) were used to knock down Asic1a and Ptgs2 expression in NSCs. The myelin sheath regeneration and axonal remyelination in rats and Asic1a-KO mice were assessed by immunofluorescence staining.ResultsFollowing injury to the spinal cord, ASIC1A was found to be colocalized and upregulated in NSCs. ASIC1A activation prevents the differentiation of NSCs into oligodendrocytes by upregulating PTGS2, which leads to increased production and release of PGE2 within extracellular vesicles (EVs). ASIC1A or PTGS2 deficiency in NSCs counters the ASIC1A-related effects on mediating NSC differentiation by reducing PGE2 expression within NSC-derived EVs. Furthermore, intervention in ASIC1A signaling by administration of ASIC1A inhibitors or genetic deletion of ASIC1A demonstrated a pronounced advantage in enhancing myelin sheath regeneration and axonal remyelination.ConclusionsThe activation of ASIC1A prevents NSC differentiation into oligodendrocytes via the transcellular NSC-to-NSC delivery of PGE2, resulting in the failure of myelin sheath regeneration and axonal remyelination following SCI. The inhibition of ASIC1A presents a promising therapeutic strategy for the treatment of SCI.Graphical

Erythropoietin Production in Embryonic Neural Cells is Controlled by Hypoxia Signaling and Histone Deacetylases with an Undifferentiated Cellular State.

During mammalian development, production sites of the erythroid growth factor erythropoietin (EPO) shift from the neural tissues to the liver in embryos and to the kidneys in adults. Embryonic neural EPO-producing (NEP) cells, a subpopulation of neuroepithelial and neural crest cells, express the Epo gene between embryonic day (E) 8.5 and E11.5 to promote primitive erythropoiesis in mice. While Epo gene expression in the liver and kidneys is induced under hypoxic conditions through hypoxia-inducible transcription factors (HIFs), the Epo gene regulatory mechanisms in NEP cells remain to be elucidated. Here, we confirmed the presence of cells co-expressing EPO and HIFs in mouse neural tubes, where the hypoxic microenvironment activates HIFs. Chemical activation and inhibition of HIFs demonstrated the hypoxic regulation of EPO expression in human fetal neural progenitors and mouse embryonic neural tissues. In addition, we found that histone deacetylase inhibitors can reactivate EPO production in cell lines derived from NEP cells and human neuroblastoma, as well as in mouse primary neural crest cells, while rejuvenating these cells. Furthermore, the ability of the rejuvenated cells to produce EPO was maintained in hypoxia. Thus, EPO production is controlled by epigenetic mechanisms and hypoxia signaling in the immature state of hypoxic NEP cells.

Viscoelastic Alginate‐Based Hydrogels: Regulating Neural Stem Cell Behavior Through Viscosity

ABSTRACTThe mechanical properties of the extracellular matrix (ECM) play a crucial role in cell adhesion, proliferation, and differentiation. In this study, a series of viscoelastic alginate‐based blend hydrogels with tunable viscosity were prepared to investigate the effects of their viscosity on the spreading and viability of NE‐4C neural stem cells. The hydrogels with the same initial modulus but different viscosities were obtained by adjusting the degree of crosslinking through covalently and ionically crosslinked techniques. The study results indicated that at a low initial modulus, an increase in the viscosity of the viscoelastic substrate could lead to a rise in the spreading area of NE‐4C neural stem cells, along with the formation of synapses, suggesting that an increase in substrate viscosity is beneficial for cell adhesion and spreading. Furthermore, the survival rate of NE‐4C neural stem cells on a high‐viscosity matrix is significantly higher than on a low‐viscosity matrix, as the high‐viscosity matrix provides a more stable microenvironment for the cells. These results can not only enhance the understanding of the effect of the viscoelasticity of biomaterials on neural stem cell behavior but also provide experimental data and theoretical support for designing new biomaterials suitable for neural tissue engineering.

Biomechanics-Function in Glaucoma: Improved Visual Field Predictions from IOP-Induced Neural Strains

Purpose(1) To assess whether neural tissue structure and biomechanics could predict functional loss in glaucoma; (2) To evaluate the importance of biomechanics in making such predictions. DesignClinic-based cross-sectional study. MethodsWe recruited 238 glaucoma subjects (Chinese ethnicity, more than 50 years old). For one eye of each subject, we imaged the optic nerve head (ONH) using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmo-dynamometry. We utilized automatic segmentation of optic nerve head (ONH) tissues and digital volume correlation (DVC) analysis to compute intraocular pressure (IOP)-induced neural tissue strains. A robust geometric deep learning approach, known as Point-Net, was employed to predict the full Humphrey 24-2 pattern standard deviation (PSD) maps from ONH structural and biomechanical information. For each point in each PSD map, we predicted whether it exhibited no defect or a PSD value of less than 5%. Predictive performance was evaluated using 5-fold cross-validation and the F1-score. We compared the model's performance with and without the inclusion of IOP-induced strains to assess the impact of biomechanics on prediction accuracy. ResultsIntegrating biomechanical (IOP-induced neural tissue strains) and structural (tissue morphology and neural tissues thickness) information yielded a significantly better predictive model (F1-score: 0.76 ± 0.02) across validation subjects, as opposed to relying only on structural information, which resulted in a significantly lower F1-score of 0.71 ± 0.02 (p < 0.05). Our subjects had a mean age of 69±5 years. Among them, 88 were female. The cohort included a wide range of glaucoma severity, with Mean Deviation (MD) values ranging from -1.8 (mild) to -25.2 (severe), and an average MD value of -7.25±5.05. ConclusionOur study has shown that the integration of biomechanical data can significantly improve the accuracy of visual field loss predictions and highlights the importance of the biomechanics-function relationship in glaucoma.

Recent Advances in Multifunctional Naturally Derived Bioadhesives for Tissue Engineering and Wound Management

ABSTRACTRecent advancements in naturally derived bioadhesives have transformed their application across diverse medical fields, including tissue engineering, wound management, and surgery. This review focuses on the innovative development and multifunctional nature of these bioadhesives, particularly emphasizing their role in enhancing adhesion performance in wet environments and optimizing mechanical properties for use in dynamic tissues. Key areas covered include the chemical and physical mechanisms of adhesion, the incorporation of multi‐adhesion strategies that combine covalent and non‐covalent bonding, and bioinspired designs mimicking natural adhesives such as those of barnacles and mussels. Additionally, the review discusses emerging applications of bioadhesives in the regeneration of musculoskeletal, cardiac, neural, and ocular tissues, highlighting the potential for bioadhesive‐based therapies in complex biological settings. Despite substantial progress, challenges such as scaling lab‐based innovations for clinical use and overcoming environmental and mechanical constraints remain critical. Ongoing research in bioadhesive technologies aims to bridge these gaps, promising significant improvements in medical adhesives tailored for diverse therapeutic needs.

Children’s Peripheral Blood Leukocytes Immune Response on Some Brain and Nervous Tissue Antigens in Vitro

Children’s Peripheral Blood Leukocytes Immune Response on Some Brain and Nervous Tissue Antigens <i>in Vitro</i>

MiR-124 in Neuroblastoma: Mechanistic Insights, Biomarker Potential, and Therapeutic Prospects

: Neuroblastoma, a malignancy predominantly affecting young children, originates from neural crest cells in the sympathetic nervous system. It primarily appears in the adrenal gland but can also affect nerve tissues in regions, such as the chest, neck, abdomen, and pelvis. Despite advancements in treatment, high-risk neuroblastoma patients often face poor prognoses, underscoring the need for ongoing research. This review paper examines the numerous factors responsible for neuroblastoma, emphasizing the importance of approaching the disorder with more strategic therapeutic methods. MicroRNAs, particularly miR-124, play critical roles in gene regulation and cancer pathogenesis. Abundant in the brain, miR-124 functions as a tumor suppressor by inhibiting cell growth, migration, and invasion and is often dysregulated in neuroblastoma. This study investigates the molecular functions of miR-124 in neuroblastoma, its potential as a biomarker, and its application in targeted therapy. MiR-124 regulates key pathways in neuroblastoma, including PI3K/AKT, TGF-β, and p53 signaling, impacting cell proliferation, apoptosis, and metastasis. The study also explores the promise of miR-124 as a biomarker for neuroblastoma through liquid biopsy, enabling non-invasive diagnosis and disease monitoring. Therapeutic strategies targeting miR-124 pathways show potential for overcoming chemotherapy resistance and improving treatment efficacy. The research underscores the significance of miR-124 in neuroblastoma, aiming to enhance early diagnosis, identify specific drug targets, and expand treatment options, ultimately improving patient outcomes.

Intraoperative neuromonitoring and mapping during spinal cord untethering surgery; a single-centre paediatric neurosurgery unit experience.

A review of intraoperative neuromonitoring (IONM) and mapping (IONMa) utility during paediatric tethered cord surgery with particular attention to feasibility, measures to prevent injury, and postoperative outcome. A retrospective analysis of spinal cord untethering surgery between 2015 and 2022 was carried out. Cohort demographics, IONM and IONMa data, and procedural details were summarised and associations between variables explored. Clinical outcome was assessed 3-months post procedure via review of medical records. One hundred and twenty-two patients (median age: 3years old: IQR: 2-9, 61% female) underwent surgery. The most common diagnosis was thickened filum (n = 59, 48%). Urological dysfunction was the most common presenting complaint (62%). Electromyography (EMG), motor evoked potentials (MEP), somatosensory evoked potentials (SSEP), and bulbocavernosus reflexes (BCR) were successfully recorded in 100%, 99%, 90%, and 73% patients. Unsuccessful BCR monitoring only occurred in females (p < 0.001). The Triggered-EMG protocol identified nerve rootlets adhered to the filum or tethering structure in 16% of the cohort. Alert criteria breaches (> 30-50% reduction in SSEP, > 80% reduction in MEP amplitude, absent BCR) occurred in 13 patients (11%). These alert criteria breaches were reversed in 11 (85%) with no permanent neurological deficits. In 2 (15%), alerts were irreversible, and one developed a permanent neurological deficit. Signs and symptoms of tethered cord had either stabilised (≥ 64%), improved (≥ 20%), or worsened (≤ 4%) at 3-month postoperative review. IONM and IONMa are useful and effective tools in monitoring and identifying neural tissue, which can guide safe cord untethering and lipoma resection. Our results validate IONM and IONMa in surgery for cord untethering.

Clinical implications of residual shunt after patent foramen ovale closure.

Residual shunt (RS) after percutaneous patent foramen ovale (PFO) closure has classically been a question of debate for controversial results about its association with increased risk of recurrent ischemic events. Different underlying processes of neural tissue injury have to be taken into account evaluating clinical impact of residual shunt after PFO closure: clotting mechanisms and non-clotting, vasoactive or oxidative mechanisms. Some biochemical studies demonstrated the importance of effective PFO closure aimed to obtain significant reduction of several molecules involved in PFO related strokes. Blood levels of serotonin and homocysteine seem to significantly decrease after percutaneous procedures. A recent study on a pro-thrombotic phenotype of migraineurs with aura and PFO demonstrated that PFO closure reduce activated platelets and thrombin at the value of healthy subjects, underlining the importance of the correct sealing of the defect. The aim of this review is to examine currently available literature studies. Different and discordant results have been obtained due to heterogeneity of study population, instrumental assessment of RS and follow-up methods and length. In the 2021 American Guidelines for the prevention of stroke, RS was definitely considered a predictor of recurrence of ischemic events. Management of this subset of patients is still an unresolved issue and more studies are encouraged.

HeMiTo-dynamics: a characterisation of mammalian prion toxicity using non-dimensionalisation, linear stability and perturbation analyses.

Prion-like proteins play crucial parts in biological processes in organisms ranging from yeast to humans. For instance, many neurodegenerative diseases are believed to be caused by the production of prion-like proteins in neural tissue. As such, understanding the dynamics of prion-like protein production is a vital step toward treating neurodegenerative disease. Mathematical models of prion-like protein dynamics show great promise as a tool for predicting disease trajectories and devising better treatment strategies for prion-related diseases. Herein, we investigate a generic model for prion-like dynamics consisting of a class of non-linear ordinary differential equations (ODEs), establishing constraints through a linear stability analysis that enforce the expected properties of mammalian prion-like toxicity. Furthermore, we identify that prion toxicity evolves through three distinct phases for which we provide analytical descriptions using perturbation analyses. Specifically, prion-toxicity is initially characterised by the healthy phase, where the dynamics are dominated by the healthy form of prions, thereafter the system enters the mixed phase, where both healthy and toxic prions interact, and lastly, the system enters the toxic phase, where toxic prions dominate, and we refer to these phases as HeMiTo-dynamics. These findings hold the potential to aid researchers in developing precise mathematical models for prion-like dynamics, enabling them to better understand underlying mechanisms and devise effective treatments for prion-related diseases.

Ethyl chloride poisoning from inhalational misuse: clinical features and outcomes

Introduction Ethyl chloride misuse remains a prevailing concern due to its accessibility, but detailed descriptions of the features of toxicity are limited to sporadic reports, resulting in knowledge gaps in their clinical features and diagnosis. Objective To describe the clinical features, treatment, and outcomes of patients reported in the literature who developed toxicity from inhalational use of ethyl chloride. Methods We reviewed relevant literature over the past 50 years and analyzed the characteristics and outcomes of patients with toxicity from the inhalational use of ethyl chloride. Results A total of 21 studies from 1979 to 2024 were identified, making available 22 patients for analysis. Their median age was 40 years (range 16–62 years), and there were more than four times as many males as females. Ethyl chloride-containing cleaning solvents (8/22, 36%) were most commonly used. Regular inhalation of ethyl chloride was documented in approximately two-thirds of the patients (14/22, 66%), with a median duration of five months of misuse (range 2–360 months). A large proportion of patients (15/22, 68%) inhaled ethyl chloride again within a week from the onset of toxicity. Although features of cerebellar dysfunction were very common at presentation (13/16, 81%), abnormalities on neuroimaging studies were rare. Death occurred in more than a quarter of cases (6/22, 27%), with patients either already deceased or dying shortly after. Half (3/6) of these deaths were directly attributable to the development of lethal cardiac dysrhythmias. Conversely, most survivors either improved or fully recovered within a few days to weeks (14/16, 88%), independent of their presenting symptoms, clinical signs, and the treatments they received. Discussion Ethyl chloride users are likely young or middle-aged males, and clinical features of toxicity can range from transient neurological symptoms to cardiac dysrhythmias and death. The prominence of neurotoxicity may be attributed to the lipophilic nature of ethyl chloride and its tendency to accumulate in neural tissue, while cardiac dysrhythmias have been attributed to cardiac sensitization to catecholamines through ethyl chloride-induced inhibition of potassium, calcium, and sodium channels. Conclusions Toxicity from the inhalational misuse of ethyl chloride should be considered in young or middle-aged males presenting with acute cerebellar dysfunction. We recommend that suspected cases undergo telemetric monitoring for 24 h, especially when tachycardia and/or palpitations are present, as deaths from lethal cardiac dysrhythmias are not uncommon.

Role of long non-coding RNAs in neurofibromatosis and Schwannomatosis: pathogenesis and therapeutic potential.

Neurofibromatosis (NF) is identified as genetic disorder characterized by multiple tumors on nerve tissues. NF1 is the most prevalent form, identified by neurofibromas and skin changes. NF1 is the most prevalent neurofibromatosis disorder, distinct from the rarer NF2 and schwannomatosis (SWN) conditions. NF2, including NF2-related SWN (NF2-SWN), predominantly involves schwannoma formation and differs from NF1 in its genetic basis and clinical presentation. Despite the established genetic basis of NF, effective treatments remain scarce. Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression, impacting pathways vital to tumor biology. This review explores the lncRNAs role in NF pathogenesis along with their potential as therapeutic targets. LncRNAs such as ANRIL and H19 show dysregulated expression in NF, influencing signaling pathways like Ras/MAPK and JAK/STAT, thereby contributing to tumor development. Understanding these interactions sheds light on the molecular mechanisms underlying NF and highlights lncRNAs as potential biomarkers of diagnosis and prognosis of NF. Additionally, therapeutic strategies targeting lncRNAs with antisense oligonucleotides (ASOs) or CRISPR-Cas9 offer promising treatment options. The present review emphasizes crucial role of lncRNAs in NF pathogenesis and their promise to create innovative treatments, aiming to improve patient outcomes and meet the urgent need for effective NF therapies.

New technology: clinical efficacy of intracapsular decompression and supported hollow screw treatment for Garden IV femoral neck fractures.

The management of Garden IV femoral neck fractures presents a formidable challenge. This study aimed to assess the safety and efficacy of a novel technological approach for treating Garden IV femoral neck fractures, involving intracapsular decompression and the utilization of supported hollow screws. Between October 2018 and October 2021, a cohort of 46 patients, comprising 25 males and 21 females, was admitted for Garden IV femoral neck fractures. The surgical intervention employed a novel methodology, involving closed reduction of femoral neck fractures on a traction bed and percutaneous implantation of decompression support hollow screw internal fixation in the capsule. Operative parameters such as intraoperative bleeding volume, incision length, and fluoroscopy frequency were recorded. Postoperative angiography was performed to evaluate the blood supply to the femoral neck and femoral head, while long-term follow-up records documented femoral neck fracture healing and patient functional recovery. The closed reduction and minimally invasive implantation of decompression support screws in the femoral neck capsule proved effective in successfully fixing Garden IV femoral neck fractures. The screw placement time was 20-45min, with an average of 25.2min. The number of fluoroscopy was 6-14, with an average of 7. The postoperative follow-up was 20-25months, with an average duration of 22months. All patients exhibited uneventful single-stage wound healing, devoid of complications such as nerve, blood vessel, or important tissue structure injuries. While femoral head necrosis occurred in one case and femoral neck shortening in another, all femoral neck fractures exhibited healing. Post-surgery, patients experienced rapid recovery, enabling early functional exercise with satisfactory functional restoration. The innovative technology, employing femoral neck capsule decompression support hollow screws, not only offers structural support, but also facilitates capsule decompression post-femoral neck fracture surgery. This approach promotes the restoration of blood flow to the femoral head and neck, accelerates fracture healing, diminishes the likelihood of femoral head necrosis, and enhances the overall therapeutic outcome for Garden IV femoral neck fractures. The merits of this novel technique warrant its widespread adoption and application.

Electroconductive Gelatin/Alginate/ Graphene Hydrogel Based Scaffold for Neural Tissue Repair

AbstractA composite polymeric scaffold of gelatin/alginate /graphene is fabricated through freeze‐drying technique. Initially, a hydrogel system comprised of gelatin/alginate (1:1) is prepared, and then the effect of different amounts of graphene carboxyl nanosheets (1,1.5, 2, and 2.5 wt.%) on the resultant structural properties are thoroughly evaluated. The swelling ratio, biodegradability, electrical and mechanical properties of bio‐composite hydrogels are controlled by manipulating the concentration of graphene‐COOH. The significant increase in the electrical conductivity is observed with the addition of 2.5% graphene‐COOH, and the electrical conductivity increased from 8.525 × 10−7 ± 0.01 S cm−1 to 7.644 × 10−4 ± 0.04 S cm−1. Also, the biocomposite hydrogels exhibited compressive and tensile strength ranging from 25 to 382 KPa and 11.4 to 148 KPa with an increase in the concentration of graphene‐COOH. The simplicity, low cost, tunable mechanical properties, and optimal electrical conductivity of the hydrogel system presented in this study highlight its potential as nerve tissue replacement.

Peripheral immune reactions following human traumatic spinal cord injury: the interplay of immune activation and suppression

Traumatic spinal cord injury (SCI) damages the nerve tissue of the spinal cord, resulting in loss of motor and/or sensory functions at and below the injury level. SCI provokes a long-lasting immune response that extends beyond the spinal cord and induces changes in the composition and function of the peripheral immune system. Seemingly contradictory findings have been observed, as both systemic immune activation, including inflammation and autoimmunity, and immune suppression have been reported. Differences in the levels and functions of various cell types and components of both the innate and adaptive immune system supporting these changes have been described at (sub)acute and chronic stages post-injury. Further research is needed for a more comprehensive understanding of the peripheral immune reactions following SCI, their possible correlations with clinical characteristics, and how these immune responses could be targeted to facilitate the therapeutic management of SCI. In this review, we provide an overview of the current literature discussing changes in the peripheral immune system and their occurrence over time following a traumatic SCI.

Realizing real-time optical molecular imaging in peripheral nerve tissue via Rhodamine B

BackgroundIatrogenic nerve injury is a consequential complication during surgery. Thus, real-time imaging of peripheral nerve (PN) possesses significant clinical implications. In recent years, the rapid advancements in optical molecular imaging (OMI) technology have provided essential technical foundations for the implementation of PN fluorescence imaging. This study aimed to realize real-time OMI of PNs via Rhodamine B.MethodsPhosphate buffered saline (PBS), normal saline (NS), 5% glucose solution (GS), and fetal bovine serum (FBS) were selected for measuring the fluorescence spectra of Rhodamine B solutions prepared in each formulation. Rhodamine B solutions, with varying doses dissolved in 100 μL of each formulation, were prepared and applied to the exposed PNs of the mice for incubation later. To ascertain the optimal formulation and dose of Rhodamine B, an analysis was performed on the signal-to-background ratio (SBR) of the nerves. Based on the experimental results, we proceeded to incubate Rhodamine B solution on the PN tissue of mice and human subjects, as well as on neuronal cells, to verify the binding sites of Rhodamine B with nerve. Subsequently, histological studies were conducted to validate the binding site between Rhodamine B and the nerves. Finally, we injected the optimal combination of Rhodamine B solution into mice via the tail vein and collected the SBR of mouse nerve tissues at different time intervals to determine the optimal pre-injection time. Fluorescence images of various tissues were collected, and Hematoxylin and Eosin (H&amp;amp;E) staining results were observed to determine the metabolism of Rhodamine B in mice and its toxicity.ResultsThe excitation peak of Rhodamine B in PBS, NS, 5% GS, and FBS formulations was 554 nm, and the emission peak was 576 nm. In PBS group, the maximum SBR was 15.37 ± 0.68 while the dose of Rhodamine B was 8 nmol. Through ex-vivo validation on fresh human nerve tissue and verification using mouse and human tissue sections, we observed fluorescent signals of Rhodamine Bin the regions of nerve tissue and the fluorescence signals were all concentrated on the neuronal cell membranes. After injection, the fluorescent signal in nerve tissue reached its peak at 24 hours (h), coinciding with the highest SBR (5.93 ± 0.92) in mouse nerve tissues at this time point. Additionally, the fluorescence signal could be maintained for at least 48 h. Within 24 h, lung dilation and fusion of alveoli occurred. Then these pathological manifestations gradually diminished, returning to normal at 2 weeks (w), with no significant acute or chronic adverse reactions observed in other tissues.ConclusionRhodamine B enables fluorescence imaging of PNs and has the potential for clinical translation.

Histopathology of thermal effects in endoscopic ear surgery: An experimental animal study.

The potential risk of thermal damage in the transcanal endoscopic ear surgery has been a concerning issue. This study aimed to investigate the histopathological effects of heat exposure of different durations in external auditory canal (EAC) skin and facial nerve tissues. This study was conducted on 20 rabbits assigned equally to five groups according to the endoscope-transmitted heat exposure duration: Control group (no exposure), 2, 10, 15, and 30 min. At the end of the procedure, EAC skin and the tympanic segment of facial nerve tissue samples were taken surgically and histopathologically examined. Significant histopathological thermal damage findings in external auditory canal skin and facial nerve tissues were observed under endoscope-transmitted heat exposure longer than 15 and 10 min, respectively. This study demonstrated that prolonged exposure of the endoscope-transmitted heat can cause histopathological thermal damage in EAC skin and facial nerve on rabbit subjects.