Search Results (5,191)

Background/Objectives: Fibromyalgia is a chronic pain syndrome with unclear etiology, meaning that it is difficult to treat effectively. The stimulation of cannabinoid receptor 1 (CB1) suppresses neuronal excitability and synaptic transmission in nociceptive pathways via reducing activity in the calcium channel and promoting the opening of the potassium channel. Methods: In this study, we examined whether CB1 activity contributes to the antinociceptive efficacy of electroacupuncture (EA) in a mouse fibromyalgia (FM) pain model established using intermittent cold stress (ICS). The model mice demonstrated both mechanical and thermal hyperalgesia measured using the von Frey and Hargreaves tests, respectively. Results: Electroacupuncture effectively reduced both forms of hyperalgesia and enhanced CB1 expression in the dorsal root ganglia, spinal cord, hypothalamus, and periaqueductal gray. In addition, EA attenuated the fibromyalgia-associated reactive transformation of microglia and astrocytes and the activation of the pain-related TLR4–MyD88–TRAF6 signaling pathway. The effects of ICS were also mitigated by the deletion of Trpv1, the gene encoding the transient receptor potential cation channel TRPV1 (capsaicin channel) implicated in nociceptive and inflammatory signaling. Further, the antinociceptive efficacy of EA was partially recapitulated by the acupoint injection of a CB1 agonist and abolished by the injection of a CB1 antagonist, suggesting that activating CB1 is essential for this therapeutic effect. Conclusions: Electroacupuncture can effectively alleviate mechanical and thermal hyperalgesia in a mouse model affected by fibromyalgia pain by activating the CB1 pathway, highlighting the therapeutic potential of CB1 agonism as a therapeutic strategy. Full article

Neuropathic pain (NP) is a debilitating chronic pain condition with complex molecular mechanisms and inadequate therapeutic solutions. This study aims to identify temporal transcriptomic changes in NP using multiple bioinformatics and machine learning algorithms. A total of 10 mouse samples (5 per group) were harvested at each time point (day three, day seven, and day fourteen), following spared nerve injury and a sham operation. Differentially expressed gene (DEG) analysis and an intersection among the three time-point groups revealed 54 common DEGs. The GO and KEGG analyses mainly showed enrichment in terms of immune response, cell migration, and signal transduction functions. In addition, the interaction of the LASSO, RF, and SVM-RFE machine learning models on 54 DEGs resulted in Ngfr and Ankrd1. The cyan module in WGCNA was selected for a time-dependent upward trend in gene expression. Then, 172 genes with time-series signatures were integrated with 54 DEGs, resulting in 11 shared DEGs. Quantitative RT-PCR validated the temporal expressions of the above genes, most of which have not been reported yet. Additionally, immune infiltration analysis revealed significant positive correlations between monocyte abundance and the identified genes. The TF-mRNA-miRNA network and drug-target network revealed potential therapeutic drugs and posttranscriptional regulatory mechanisms. In conclusion, this study explores genes with time-series signatures as biomarkers in the development and maintenance of NP, potentially revealing novel targets for analgesics. Full article

Background: Deferred cord clamping (DCC) is beneficial for preterm infants, but there are concerns about the safety of DCC during Cesarean deliveries (CD) under general anesthesia (GA). We evaluated maternal and neonatal outcomes in preterm CD under GA vs. regional anesthesia (RA) after implementing 180 s of DCC. Methods: This retrospective single-center observational study included CD at <33 weeks gestation, delivered between January 2018 and December 2023. The cord was clamped before 180 s for concerns of maternal bleeding or infant apnea after 30–45 s stimulation. Data was collected from reports from electronic medical records, neonatal intensive care unit database, and manually from the medical records of the patient. Multivariable regression analysis was used to assess the effect of anesthesia type and DCC on outcomes, adjusting for confounders. Results: This study included 170 mothers and 194 infants, and 84.9% of the infants received DCC ≥ 60 s. The GA group had a higher percentage of emergency CD and a lower median duration of DCC (105 s vs. 180 s, p ≤ 0.001) compared to RA. In multivariate regression analysis, GA was associated with lower odds (95% CI) of umbilical artery pH < 7 [0.1, (0.0, 0.6)], base deficit ≥ 16 [0.0, (0.0, 0.5)], and higher odds of necrotizing enterocolitis [28.2, (1.4, 560.0)]. GA was not associated with maternal hemorrhage, delivery room (DR) resuscitation, or other major neonatal morbidities or mortality. DCC ≥ 60 s was associated with lower maternal blood loss [Regression coefficient −698, (−1193, −202)], lower odds of transfusion [0.4, (0.1, 1.0)], DR resuscitation [0.4, (0.2, 0.8)], and chronic lung disease [0.4, (0.2, 0.9)], and higher survival without major morbidities [2.8, (1.2, 6.8)]. Conclusions: DCC was performed in a majority of CD under GA by adhering to protocols to shorten DCC in cases where maternal or fetal safety was threatened. GA with DCC was not associated with increased neonatal resuscitation or major neonatal morbidities and was associated with lower maternal hemorrhage and transfusion. Full article

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy may have effects on the offspring epigenome. And the change in onset epigenome may be associated with children’s neurodevelopment. The current study investigated the relationship between 5-hydroxymethylcytosine (5-hmC) levels in cord blood and PAH metabolites in maternal urine at delivery and children’s neurodevelopment at birth and at age 2. We enrolled 400 pregnant women and their newborns and collected their biological samples after obtaining written informed consent. Enzyme linked immunosorbent assay kits and Chromatin immunoprecipitation kits were used to assess the DNA hydroxymethylation level in cord blood. We observed that 1-hydroxypyrene (1-OHPyr) was inversely associated with gesell developmental scale scores, positively associated with global DNA 5-hmC levels, and associated with decreased 5-hmC levels of the brain-derived neurotrophic factor (BDNF) and methyl CpG binding protein 2 (MeCP2) gene promoter. In addition, the 5-hmC levels of the BDNF and MeCP2 gene promoters were associated with motor scores. The global DNA 5-hmC was inversely associated with motor scores. Mediation analysis showed mediation effects between 1-OHPyr and motor scores by 5-hmC. The global DNA 5-hmC and MeCP2 and BDNF gene promoter 5-hmC contributed 28.51%, 27.29%, and 18.98% of the effect on motor scores changes related to 1-OHPyr. The study results suggested that 5-hmC can be a potential mechanism between prenatal PAH exposure and children’s neurodevelopment at age 2 and provide a better understanding of the role of hydroxymethylation in neurodevelopment. Full article

After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute to abnormalities during regeneration is poorly understood. Here, we addressed this question with a low-thoracic compression injury mouse model. The total numbers of immunohistochemically stained neuronal and glial cell types in the lumbar spinal cord were stereologically determined 6 weeks after injury. We also investigated injured mice deficient in close homolog of L1 (CHL1), which had been reported to recover better after injury than their wild-type littermates. We here report that there were no differences between genotypes in uninjured animals. In both injured CHL1-deficient and wild-type littermates, gray and white matter volumes were decreased as compared with uninjured mice. Numbers of motoneurons and parvalbumin-expressing interneurons were also reduced in both genotypes. Numbers of interneurons in injured mutant mice were lower than in wild-type littermates. Whereas injury did not affect numbers of astrocytes and oligodendrocytes in the gray matter, numbers of microglia/macrophages were increased. In the mutant white matter, numbers of oligodendrocytes were reduced, with no changes in numbers of astrocytes and microglia. A loss of motoneurons and interneurons was observed in both genotypes, but loss of interneurons was more prominent in the absence of CHL1. We propose that, after injury, CHL1 deficiency causes deficits in structural outcome not seen after injury of wild-type mice. Full article

Gestational diabetes mellitus (GDM) is a growing global health concern, driving the need for novel diagnostic and prognostic approaches. The aim of this study was to analyze the amino acid profile in the mother–fetus system (maternal venous blood, umbilical cord blood, and amniotic fluid) and to identify specific biological markers of GDM and macrosomia. Using HPLC-MS/MS, we analyzed serum from maternal venous and umbilical cord blood, along with amniotic fluid, across 94 mother–fetus pairs (53 GDM, 41 controls). Machine learning and metabolic pathway analysis revealed significant alterations in 19 amino acids. In GDM, maternal serum showed elevated 5-OH-lysine and homocitrulline, while cord blood had higher isoleucine, serine, and threonine. Amniotic fluid exhibited increased leucine, isoleucine, threonine, serine, arginine, and ornithine. Conversely, histidine, glutamine, alanine, asparagine, β-/γ-aminobutyric acids, phenylalanine, ornithine, and citrulline were reduced. Histidine, glutamine, and asparagine inversely correlated with blood glucose (r = −0.26, r = −0.33, r = −0.30) and were lower in GDM. These findings highlight three key metabolic loci in GDM pathogenesis, with glutamine, histidine, and asparagine emerging as potential maternal blood biomarkers for early macrosomia prediction. However, given confounding factors in metabolomic studies, further large-scale validation is essential. Full article

Background: multiple sclerosis (MS) presentation varies depending on the location and severity of the lesions affecting different areas of the spinal cord and brain. Extensive research has focused on specific systems to detect the disease in its various stages. The objective of this study was to investigate the concentration of the soluble scavenger receptor for haptoglobin–haemoglobin complex (Hb-Hp), sCD163, which is mostly expressed by monocytes and protects tissues from oxidative damage, in patients with MS. Methods: enzyme-Linked Immunosorbent Assay (ELISA) analysis was conducted in plasma samples collected from twenty-three relapsing–remitting MS (RRMS) subjects treated with teriflunomide and ten healthy control subjects (HCs). Results: the study results showed no differences between RRMS subjects and HCs in the concentration of CD163. A significantly higher concentration of sCD163 in RRMS was found in men in comparison to women (p = 0.038, Cohen d = 0.97). Conclusions: a significant correlation between disease activity, estimated using plasma-soluble CD163 (sCD163) and clinical assessment of the Expanded Disability Status Scale (EDSS) (p = 0.021), was detected in female patients with RRMS. Full article

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease. Evidence on the efficacy of different mesenchymal stem cell (MSC) exosomes for psoriasis remains limited. This study aimed to evaluate the therapeutic effects of different MSC exosomes in mitigating psoriasis. Methods: The efficacy of human placenta MSC (hPMSC) and human umbilical cord MSC (hUCMSC) exosomes was compared in an imiquimod (IMQ)-induced psoriasis murine model. A meta-analysis was performed to incorporate the results of studies using IMQ-induced psoriasis murine models to compare MSC exosome treatments (exosome group) with vehicle or no-treatment controls (control group). Results: In this murine study, both the hPMSC and hUCMSC exosomes showed better effectiveness in reducing epidermal thickness and skin tissue cytokines than controls, but no significant difference was observed between the two MSC exosomes. Seven studies were included in the meta-analysis. Clinical severity scores were significantly lower in the exosome group than in the controls (standardized mean difference [SMD]: −1.886; 95% confidence interval [CI]: −3.047 to −0.724). Epidermal thickness was significantly reduced (SMD: −3.258; 95% CI: −4.987 to −1.529). No significant differences were found in most skin cytokines between the groups, although tumor necrosis factor-α mRNA (SMD: −0.880; 95% CI: −1.623 to −0.136) and interleukin-17A protein levels (SMD: −2.390; 95% CI: −4.522 to −0.258) were both lower in the exosome group. Meta-regression revealed a greater improvement in clinical scores in studies using hUCMSC exosomes compared to other MSC sources (p = 0.030). Conclusions: hUCMSC exosomes have been studied more extensively than other MSC exosomes. MSC exosomes reduce clinical severity and epidermal hyperplasia. Full article

Transverse myelitis is a rare spinal cord condition that can cause severe motor, sensory, and autonomic dysfunction. This case report describes a 16-year-old male with incomplete paraplegia due to idiopathic transverse myelitis who underwent robotic-assisted gait training (RAGT) using the EKSO exoskeleton, integrated into an intensive rehabilitation programme. After one month, he showed significant improvements in gait speed, dynamic balance, effort tolerance, and trunk mobility. RAGT promoted better weight distribution and reduced compensatory patterns during ambulation. The intervention proved safe and clinically beneficial, highlighting the potential of robotic technologies as effective adjuncts in paediatric spinal cord injury rehabilitation. Full article

Spinal cord injury (SCI) results in significant motor, sensory, and autonomic dysfunction. The pathophysiology of SCI develops during the primary and secondary phases. Inflammation contributes to the secondary phase through the non-specific activation of the innate immune response. Glial scar formation (gliosis), a reactive cellular mechanism facilitated by astrocytes, also occurs during this phase. Synthetic steroids such as tibolone (Tib) have been proposed as a treatment for SCI since they exert neuroprotective effects in various models of central nervous system (CNS) injury. We studied the effect of Tib on locomotor functional recovery and the regulation of neuroinflammation and gliosis in an SCI model. We performed an SCI at the thoracic vertebrae nine in male Sprague Dawley rats. The animals received daily doses of Tib (1 or 2.5 mg per kg of body weight) administered orally. We quantified pro- and anti-inflammatory cytokine levels at the injury site and determined motor recovery using the Basso, Beattie, and Bresnahan (BBB) scale. Finally, we investigated the effect of Tib on the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), two markers of gliosis, using an immunohistochemistry assay. Our findings showed that Tib regulated pro- and anti-inflammatory cytokine levels at 3 h and 3, 7, and 14 days post-SCI. Furthermore, Tib administered orally for 15 days reduced gliosis markers and favored tissue preservation and motor function recovery after SCI. Full article

Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost entirely by partial left-sided heart or total cardiopulmonary bypass with extra-corporeal circulation (ECC). Despite several advantages of these methods, PS still has potential in mitigating some drawbacks of long extracorporeal circuits connected with centrifugal or roller pumps, such as the need for cardiac and great vessels cannulation, priming and large intravascular fluid volume shifts, high heparin dose, immunosuppressive effects, and systemic inflammatory response syndrome. Methods: This study prospectively analyzed data of a cohort of patients who underwent TAAA OR using a PS in a single institution. Outcomes of interest were mortality, rate of mesenteric, renal and spinal cord ischemia, cardiac complications, and intraoperative hemodynamic stability achieved in this setting. Our institutional bundle and a comprehensive literature review about the different configurations and applicability of PS for TAAA OR is also reported. The search was performed based on three databases (PubMed, EMBASE, and Cochrane Library) by two independent reviewers (LS and AA) from inception to 31 December 2023, and the reported clinical results (visceral, renal, and spinal cord complications and mortality) using PS during TAAAs OR were analyzed. Results: Between March 2021 and December 2023, 51 TAAA repairs were performed and eleven patients (n = 8, 73% male; mean age 67 years, range 63–79) were operated using a PS for a total of one (9%) type I, one (9%) type II, two (18%) type III, five (45%) type IV, and two (18%) type V TAAA. In our early experience, PS was indicated for limited staff resources during the COVID-19 pandemic to treat five non-deferable cases. The sixth and seventh patients were selected for PS as they already had a functioning axillo-bifemoral bypass that was used for this purpose. For the most recent cases, PS was chosen as the primary perfusion method according to a score based on clinical and anatomical factors with ECC as a bailout strategy. Selective renal perfusion with cold (4 °C) Custodiol solution was the method of choice for renal protection in all cases while antegrade perfusion of the coeliac trunk and the superior mesenteric artery was assured by PS through a loop graft (8–10mm) proximally anastomosed to the axillary artery (10 patients, 90.9%) or the descending thoracic aorta (one patient, 9%) and distally anastomosed to the infrarenal aorta (3), common iliac (3), or femoral vessels (5). In-hospital mortality was 9% as one patient died on the 10th postoperative day from mesenteric ischemia following hemodynamic instability; permanent spinal cord ischemia rate was 0% and the rate of AKI stage 3 was 9% (one patient). Bailout shifting to ECC was never required. No cardiac complications, nor a significant increase in serum CK-MB were reported in any patient. No prolonged severe intraoperative hypotension episodes (Mean Arterial Pressure < 50 mmHg) were assessed using the Software Acumen Analytics (Edwards LifeSciences, Irvine CA, USA). No peri-operative coagulopathy nor major bleeding was reported. Conclusions: Our experience showed satisfactory outcomes with the use of PS in specifically selected cases. Current data indicate that PS may represent an alternative to ECC techniques during TAAAs OR in high volume centers where assisted extracorporeal circulation could eventually be applied as a bailout strategy. However, due to the small sample size of this and previously published series, more data are needed to clearly define the potential role of such approach during TAAA OR. Full article

This in vitro study evaluated the internal surface trueness and the marginal and internal fit of interim crowns fabricated from intraoral scanner (IOS; i500, MEDIT, Seoul, Republic of Korea) data, considering variations in subgingival finish line depth and the use of gingival retraction. A right maxillary first molar was prepared using a milled ceramic abutment, with subgingival finish line depths set at 0, 0.25, 0.50, 0.75, and 1.00 mm from the gingival crest. All specimens were scanned with an IOS, both with and without gingival retraction. Interim crowns were designed from the scan data and produced via three-dimensional (3D) printing. Internal surface trueness was measured using 3D inspection software (Geomagic Control X version 2022.0.0; 3D Systems, Rock Hill, SC, USA), while marginal and internal fit were assessed with the silicone replica technique. Data were analyzed using the Mann–Whitney U test and Kruskal–Wallis H test (α = 0.05). In the absence of gingival retraction, internal surface trueness and crown fit decreased significantly with increasing finish line depth (p < 0.05). At a 1.00 mm depth without retraction, internal trueness reached 100.1 ± 44.5 µm and marginal fit was 189.1 ± 42.2 µm, both exceeding clinical thresholds. With gingival retraction, trueness and fit remained stable across all depths (p > 0.05). At 1.0 mm depth, trueness was 82.0 ± 61.8 µm and marginal fit was 95.2 ± 22.9 µm, both within clinically acceptable limits. A significant correlation was observed between marginal trueness and overall fit when retraction was not performed (p < 0.05). These results demonstrate that increasing subgingival finish line depth can significantly reduce intraoral scanning accuracy, resulting in suboptimal interim crown adaptation when gingival retraction is omitted. To achieve clinically acceptable internal trueness and marginal fit, gingival displacement with a retraction cord is recommended during intraoral scanning for subgingival prosthesis fabrication. Full article

Regulatory T cells (Tregs) have anti-inflammatory immunomodulatory activity and hold therapeutic potential for chronic neuroinflammatory neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). We are developing engineered human Tregs with enhanced disease-modifying activity for treating ALS. A combination of a disease-specific chimeric antigen receptor (CAR) recognizing misfolded human superoxide dismutase-1 (hSOD1) and constitutive expression of brain-derived neurotrophic factor (BDNF) was tested. The scFv region of CAR demonstrated binding to anterior horn tissues of ALS patients with and without familial ALS mutations in SOD1. Tregs transduced to express BDNF showed the ability to secrete BDNF and protect co-cultured neuronal cells from peroxidase toxicity. Co-expression of BDNF did not inhibit CAR Treg expansion, Treg markers, or CAR-mediated anti-inflammatory cytokine production. Human Tregs co-expressing CAR and BDNF were tested for activity in G93A hSOD1-NSG transgenic mice, which develop an early-onset and aggressive ALS-like disease and do not reject human cells. Human Tregs expressing CAR and BDNF delayed the onset of disease development, extended survival, and decreased spinal cord neuroinflammation. The engineered Tregs showed enhanced disease-modifying activity and hold promise as a therapy for ALS. Full article

Neurosurgery is undergoing a significant transformation driven by advances in biomaterials and tissue engineering. These interdisciplinary innovations address challenges in repairing and regenerating neural tissues, integrating cranial and spinal implants, and improving patient outcomes. The incidence of neurological injuries such as traumatic brain injury and spinal cord injury remains high, underscoring the need for improved therapeutic strategies. This review provides a comprehensive overview of current biomaterial and tissue engineering approaches in neurosurgery, highlighting developments in neural tissue repair, cranial and spinal implants, spinal cord injury treatment, and peripheral nerve regeneration. Key challenges—such as ensuring biocompatibility, modulating the immune response, and bridging the gap between laboratory research and clinical application—are discussed. Emerging technologies including 3D bioprinting, nanotechnology (removing microfluidics), and microfluidics are examined for their potential to revolutionize neurosurgical treatments. The need for interdisciplinary collaboration among neurosurgeons, material scientists, and biologists is emphasized as critical for overcoming translational barriers and accelerating the clinical translation of these promising technologies. Full article