Search Results (1,270)

Background/Objectives: We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Methods: Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed. Results: Considerable between and within-subject variation was observed. Sacral (S) ventral rami contributions to vesical nerves were observed as shared contributions from several rami or, in a few cases, from single rami: S2 alone (6%), S3 alone (6%), S2 and S3 (28%), S3 and S4 (28%), S2–S4, 14%, L5 in combination with S1–S4 (6%), S1 and S2 (6%), and S3–S5 (3%). The most common contributor to these shared or single rami contributions was from the S3 ventral ramus, which contributed 100% of the time on the left side and 79% on the right side. Side-to-side asymmetry was observed in 10 of 14 cadavers examined bilaterally (71%). Conclusions: This characterization of the anatomical variation in sacral ventral rami contributions to the bladder will ultimately aid in developing therapeutics for patients with bladder dysfunction. Full article

Background/Objectives: This study assessed the efficacy of photobiomodulation therapy (PBM) by 808 nm and 660 nm alone and in combination for the treatment of paresthesia in rats. Methods: This animal study was conducted on 36 adult male Wistar rats. After general anesthesia, the facial nerve of the right side of the face of rats was surgically exposed and pinched, returned in place, and sutured. The rats were randomly assigned to six groups (n = 6) of (I) no-intervention (control), (II) no-laser, (III) 808 nm laser (250 mW, 4 W/cm², 20 s, 8 J/cm², (IV) 660 nm laser (150 mW, 0.25 W/cm², 32 s, 8 J/cm², (V) 808 nm plus 660 nm laser with the original settings, and (VI) 808 nm plus 660 nm laser with half of the time and energy density. After 16 days, a biopsy sample was taken from the nerve injury site and underwent histological, histometric, and immunohistochemical assessments. Results: Significantly lower edema and congestion were seen in the combined laser group with original settings (p < 0.05); this group had no significant difference with the control group regarding degenerative changes of the nerve fibers and Schwann cells (p > 0.05). The 660 nm, and combined laser groups, had a significantly lower accumulation of inflammatory cells (p < 0.05). The number of blood vessels in combined laser groups was significantly lower than that in the no-laser group (p < 0.05). Conclusions: The results showed the positive efficacy of PBM by 808 nm and 660 nm lasers in resolution of inflammation and reduction of degenerative changes of Schwann cells and nerve fibers. Full article

CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4–L5) and cervical (C7–C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons. The role of CXCR4 signaling in the axon-promoting state of DRG neurons was confirmed through in vitro cultivation of primary sensory neurons in a medium supplemented with CXCL12, with or without AMD3100. The potential involvement of conditioned cervical DRG neurons in the induction of neuropathic pain is discussed. Full article

Skull base tumors such as meningiomas and schwannomas are often pathologically benign. However, surgery for these tumors poses significant challenges because of their proximity to critical structures such as the brainstem, cerebral arteries, veins, and cranial nerves. These structures are compressed or encased by the tumor as they grow, increasing the risk of unintended injury to these structures, which can potentially lead to severe neurological deficits. Preoperative imaging is crucial for assessing the tumor size, location, and its relationship with adjacent vital structures. This study reviews advanced imaging techniques that allow detailed visualization of vascular structures and cranial nerves. Contrast-enhanced computed tomography and digital subtraction angiography are optimal for evaluating vascular structures, whereas magnetic resonance imaging (MRI) with high-resolution T2-weighted images and diffusion tensor imaging are optimal for evaluating cranial nerves. These methods help surgeons plan tumor resection strategies, including surgical approaches, more precisely. An accurate preoperative assessment can contribute to safe tumor resection and preserve neurological function. Additionally, we report the MRI contrast defect sign in skull base meningiomas, which suggests cranial nerve penetration through the tumor. This is an essential finding for inferring the course of cranial nerves completely encased within the tumor. These preoperative imaging techniques have the potential to improve the outcomes of patients with skull base tumors. Furthermore, this study highlights the importance of multimodal imaging approaches and discusses future directions for imaging technology that could further develop preoperative surgical simulations and improve the quality of complex skull base tumor surgeries. Full article

Background: Thyroidectomy, a surgical procedure for thyroid disorders, is associated with postoperative voice changes, even in cases without recurrent laryngeal nerve (RLN) injury. Our study evaluates the prevalence and predictors of voice disorders in thyroidectomy patients without RLN injury. Methods: Our single-center prospective study at the University Hospital Center Zagreb included 243 patients, with pre- and postoperative voice evaluations using acoustic analysis and videostroboscopy. Logistic regression, chi-square, MANOVA, and non-parametric tests assessed the impact of surgical, sociodemographic, and lifestyle factors. Results: The study analyzed 243 participants (141 lobectomy, 102 total thyroidectomy). Postoperative voice disorders occurred in 200 patients (100 lobectomy, 100 total thyroidectomy); 43 (17.7%) experienced no voice disorders. Significant associations were observed for surgery type (χ² = 29.88, p < 0.001), with total thyroidectomy having higher risk, surgery duration (χ² = 16.40, p < 0.001), thyroid volume (χ² = 4.24, p = 0.045), and BMI (χ² = 8.97, p = 0.011). Gender and age showed no significant correlation. Acoustic parameters differed significantly, with lobectomy patients showing better intensity, jitter, and shimmer values across postoperative measurements. Logistic regression identified surgery type (Exp(B) = 16.533, p = 0.001) and thyroid volume (Exp(B) = 2.335, p = 0.023) as predictors of voice disorders, achieving 82.7% classification accuracy. Multivariate analysis confirmed gender and surgery duration as significant contributors. Surgery duration exceeding 90 min and enlarged thyroid volume negatively influenced outcomes. Significant acoustic differences were also linked to BMI categories, with obese participants exhibiting poorer parameters, particularly shimmer and jitter. Conclusions: Surgery type, thyroid volume, BMI, and surgery duration are most likely significant predictors of postoperative voice disorders. Full article

In general, the nerve cells of the peripheral nervous system regenerate normally within a certain period after the physical damage of their axon. However, when peripheral nerves are transected by trauma or tissue extraction for cancer treatment, spontaneous nerve regeneration cannot occur. Therefore, it is necessary to perform microsurgery to connect the transected nerve directly or insert a nerve conduit to connect it. In this study, we applied human tonsillar mesenchymal stem cell (TMSC)-derived Schwann cell-like cells (TMSC-SCs) to facilitate nerve regeneration and prevent muscle atrophy after neurorrhaphy. The TMSC-SCs were manufactured in a good manufacturing practice facility and termed neuronal regeneration-promoting cells (NRPCs). A rat model of peripheral nerve injury (PNI) was generated and a mixture of NRPCs and fibrin glue was transplanted into the injured nerve after neurorrhaphy. The application of NRPCs and fibrin glue led to the efficient induction of sciatic nerve regeneration, with the sparing of gastrocnemius muscles and neuromuscular junctions. This sparing effect of NRPCs toward neuromuscular junctions might prevent muscle atrophy after neurorrhaphy. These results suggest that a mixture of NRPCs and fibrin glue may be a therapeutic candidate to enable peripheral nerve and muscle regeneration in the context of neurorrhaphy in patients with PNI. Full article

Objectives: We aimed to create a predictive model to estimate sciatic nerve depth using anthropometric and demographic data to enhance safety and precession in needle-based interventions. Setting: The study was conducted at Universidad Europea de Madrid, Spain. Methods: A Cross-sectional observational study was carried out between January and April 2024. The study included fifty volunteers aged 18–45 years, without any muscle tone affections, lower limb asymmetries, or history of lower limb surgeries. Demographic and anthropometric data were collected, including sex, age, height, weight, BMI, and leg length measure and thigh circumference at specific points. The sciatic nerve depth was measured using ultrasound imaging under the gluteal fold and in the posterior middle third of the thigh. Results: Correlation analysis revealed significant associations between thigh circumference at the proximal and middle third and sciatic nerve depth. A multiple linear regression model identified that the proximal thigh circumference was a significant predictor of sciatic nerve depth, explaining 44.5% of the variance. The variance increased to 49.7% when gender was added. The depth of the sciatic nerve in the middle third explained 38.2% of the variance. And the inclusion of gender in the model explained 40.8% of the variance for the middle third. Conclusions: This study identify significant predictors such as the thigh girth at the proximal and mid-third levels, gender, and the BMI. These findings suggest that clinicians can use these anthropometric measurements to estimate sciatic nerve depth more accurately, reducing the risk of accidental nerve injury and improve the precision and safety of needling procedures during invasive procedures. Full article

Background and Objectives: The aim was to evaluate nerve healing using immunohistochemical, histological, and functional techniques and to compare the effects of two different therapeutic ozone application methods by perineural and intraperitoneal ozone treatment in rats with a crush injury model of sciatic nerve. Materials and Methods: Forty male Sprague Dawley rats were divided into four subgroups of ten rats each: (1) Control group: The left sciatic nerve incised and closed without crush injury, no treatment; (2) Paralyzed group: Crush injury to the left sciatic nerve, no treatment; (3) Perineural ozone group: Crush injury to the left sciatic nerve, treated with perineural ozone therapy; (4) Intraperitoneal ozone group: Crush injury to the left sciatic nerve, treated with intraperitoneal ozone therapy. The treatments were administered for a 14-day period. Hematoxylin and eosin (H&E) and toluidine blue staining were used for histological examination; TUNEL staining was used for immunohistochemical examination. Pinch test and rotarod performance assessment were utilized for functional evaluation. Results: The pinch test scores showed significant improvement in perineural and intraperitoneal ozone treatment groups after treatment (p < 0.001 and p = 0.003, respectively). The scores of myelin degeneration, vascular congestion, vascular wall thickness, inflammation, and toluidine blue and TUNEL staining were significantly lower in both ozone treatment groups compared to the paralyzed group (p < 0.001). Vascular wall thickness scores were significantly higher in the perineural ozone group compared to the control and intraperitoneal ozone groups (p = 0.004 and p = 0.013, respectively). The Schwann cell proliferation scores were significantly higher in the perineural ozone group compared to the control group and intraperitoneal ozone groups (p < 0.001). Conclusions: Both applications of ozone therapy accelerated the healing of nerve regeneration, reduced inflammation and apoptosis based on histopathological results, and enhanced nerve function in rats with sciatic nerve injury. Perineural ozone therapy has been demonstrated to be an efficacious alternative to systemic ozone treatments in the management of sciatic nerve injury. Further studies are needed to determine optimal ozone dosage and administration protocols for the treatment of nerve injury. Full article

Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPKα1 activation is crucial. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Myeloid-specific AMPKα1 KO mice were generated by crossing AMPKα1^Flox/Flox and LysM^cre to carry out the study. We induced TON in mice by using a controlled impact system. Mice (mixed sex) were randomized in six experimental groups for Sham (mock); Sham (RIC); AMPKα1^F/F (TON); AMPKα1^F/F (TON+RIC); AMPKα1^F/F LysM^Cre (TON); AMPKα1^F/F LysM^Cre (TON+RIC). RIC therapy was given every day (5–7 days following TON). Data were generated by using Western blotting (pAMPKα1, ICAM1, Brn3 and GAP43), immunofluorescence (pAMPKα1, cd11b, TMEM119 and ICAM1), flow cytometry (CD11b, F4/80, CD68, CD206, IL-10 and LY6G), ELISA (TNF-α and IL-10) and transmission electron microscopy (TEM, for demyelination and axonal degeneration), and retinal oxygenation was measured by a Unisense sensor system. First, we observed retinal morphology with funduscopic images and found TON has vascular inflammation. H&E staining data suggested that TON increased retinal inflammation and RIC attenuates retinal ganglion cell death. Immunofluorescence and Western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in the TON [AMPKα1^F/F] vs. Sham group, but TON+RIC [AMPKα1^F/F] attenuated the expression level of these markers. Interestingly, higher microglia activation was observed in the myeloid AMPKα1^F/F KO group following TON, and RIC therapy did not attenuate microglial expression. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers, increased anti-inflammatory macrophage polarization and improved oxygen level in the TON+RIC [AMPKα1^F/F] group; however, RIC therapy did not reduce inflammatory signaling activation in the myeloid AMPKα1 KO mice. The transmission electron microscopy (TEM) data of the optic nerve showed increased demyelination and axonal degeneration in the TON [AMPKα1^F/F] group, and RIC improved the myelination process in TON [AMPKα1^F/F], but RIC had no significant effect in the AMPKα1 KO mice. The myeloid AMPKα1c deletion attenuated RIC induced anti-inflammatory macrophage polarization, and that suggests a molecular link between RIC and immune activation. Overall, these data suggest that RIC therapy provided protection against inflammation and neurodegeneration via myeloid AMPKα1 activation, but the deletion of myeloid AMPKα1 is not protective in TON. Further investigation of RIC and AMPKα1 signaling is warranted in TON. Full article

The failure of endogenous repair mechanisms is a key characteristic of neurological diseases, leading to the inability to restore damaged nerves and resulting in functional impairments. Since the endogenously regenerative capacity of damaged nerves is limited, the enhancement of regenerative potential of quiescent neural stem cells (NSCs) presents as a therapeutic option for neural diseases. Our previous studies have shown exciting progress in treating sciatic nerve injury in mice and rats using NSCs in conjunction with neurotrophic factors such as fibroblast growth factor 1 (FGF1). Additionally, a recently discovered neurotrophic factor, IL12p80, has shown significant therapeutic effects in sciatic nerve injury repair via myelinating oligodendrocytes. IL12p80 induces oligodendrocyte differentiation from NSCs through phosphorylation of Stat3. Therefore, it might be possible to alleviate the myelination defects of oligodendrocytes in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and even schizophrenia through the administration of IL12p80. These applications could shed light on IL12p80 and FGF1, not only in damaged nerve repair, but also in rectifying the oligodendrocytes’ defects in neurodegenerative diseases, such as ALS and MS. Finally, the synergistic effects of neurogenesis-induced FGF1 and myelination-induced IL12 might be able to supplant the need of NSCs for nerve repair and neuroregeneration. Full article

Background and Objectives: This study investigated associated meniscus and ligament injuries in tibial plateau fractures using magnetic resonance imaging (MRI) and assessed soft tissue injuries in relation to the Schatzker classification and Tscherne classification. Materials and Methods: The data of 185 patients who sustained tibial plateau fractures from January 2010 to April 2021 were retrospectively reviewed. Fractures were classified according to the Schatzker classification system. Soft-tissue injuries were assessed using the Tscherne classification. Menisci and ligaments were evaluated using preoperative MRI. Nerve injuries, compartment syndrome and wound problems were also assessed. The incidence of soft tissue injuries, as well as the relationship between the Schatzker and Tscherne classification systems, were analyzed. Results: Evidence of derangement of meniscus and ligament around the knee was found in 183 (98.9%) patients. The most common injury was a medial collateral ligament injury. The incidence of lateral collateral ligament injury, nerve injury, compartment syndrome and wound problem was higher in high-energy tibial plateau fractures. A tendency was observed between the Schatzker and the Tscherne classifications (p value < 0.001). Higher Tscherne grade was also associated with the incidence of posterior cruciate ligament injury, nerve injury and compartment syndrome. Conclusions: In tibial plateau fractures, soft tissue injuries were highly prevalent. High-energy fractures tended to exhibit higher Tscherne classification grades and showed an increased incidence of meniscus and ligament injuries. The Tscherne classification appears to be a helpful system for predicting soft tissue injuries in tibial plateau fractures. And preoperative MRI can be a helpful tool. Full article

Metabolic dysfunction has been demonstrated to contribute to diabetic pain, pointing towards a potential correlation between glucose metabolism and pain. To investigate the relationship between altered glucose metabolism and neuropathic pain, we compared samples from healthy subjects with those from intervertebral disc degeneration (IVDD) patients, utilizing data from two public datasets. This led to the identification of 412 differentially expressed genes (DEG), of which 234 were upregulated and 178 were downregulated. Among these, three key genes (Ins, Igfbp3, Plod2) were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated the enrichment of hub genes in pathways such as the positive regulation of the ErbB signaling pathway, monocyte activation, and response to reactive oxygen species; thereby suggesting a potential correlation between these biological pathways and pain sensation. Further analysis identified three key genes (Ins, Igfbp3, and Plod2), which showed significant correlations with immune cell infiltration, suggesting their roles in modulating pain through immune response. To validate our findings, quantitative real-time polymerase chain reaction (qPCR) analysis confirmed the expression levels of these genes in a partial sciatic nerve ligation (PSNL) model, and immunofluorescence studies demonstrated increased immune cell infiltration at the injury site. Behavioral assessments further corroborated pain hypersensitivity in neuropathic pain (NP) models. Our study sheds light on the molecular mechanisms underlying NP and aids the identification of potential therapeutic targets for future drug development. Full article

Recurrent laryngeal nerve palsy remains a significant complication following minimally invasive esophagectomy for esophageal cancer. Despite advancements in surgical techniques and lymphadenectomy precision, the incidence of recurrent laryngeal nerve palsy has not been improved. Recurrent laryngeal nerve palsy predominantly affects the left side and may lead to unilateral or bilateral vocal cord paralysis, resulting in hoarseness, dysphagia, and an increased risk of aspiration pneumonia. While most cases of recurrent laryngeal nerve palsy are temporary and resolve within 6 to 12 months, some patients may experience permanent nerve dysfunction, severely impacting their quality of life. Prevention strategies, such as nerve integrity monitoring, robotic-assisted minimally invasive esophagectomy, and advanced dissection techniques, aim to minimize nerve injury, though their effectiveness varies. The management of recurrent laryngeal nerve palsy includes voice and swallowing rehabilitation, reinnervation techniques, and, in severe cases, surgical interventions such as thyroplasty and intracordal injection. As recurrent laryngeal nerve palsy can lead to significant postoperative respiratory complications, a multidisciplinary approach involving surgical precision, early detection, and comprehensive rehabilitation is crucial to improving patient outcomes and minimizing long-term morbidity in minimally invasive esophagectomy. This review article aims to inform esophageal surgeons and other clinicians about strategies for the prevention and management of recurrent laryngeal nerve palsy in esophagectomy. Full article

Background/Objectives: Thermotherapy is expected to assist in the prevention of arteriosclerosis and cardiovascular disease in individuals with spinal cord injuries. This study aimed to investigate the impact and underlying mechanisms of whole-body heat stress on cardiac function in patients with cervical spinal cord injury (CSCI) and healthy controls using head-out hot water immersion (HHWI). Methods: Eight male patients with complete motor CSCI and nine healthy controls were recruited. Participants were immersed for 60 min in water set at 2 °C above the resting esophageal temperature. Esophageal temperature, heart rate, and arterial pressure were monitored throughout the experiment. Before and after HHWI, echocardiography was used to measure indices of left ventricular diastolic capacity (E, E′, and A), left atrial contractility (A and A′), and left ventricular contractility [S′ and isovolumic acceleration (IVA)]. Results: Both groups exhibited an increase in body temperature and heart rate, while blood pressure remained stable. In the control group, there was a significant increase in E (67.0 ± 22.6 to 89.1 ± 13.6), E′ (9.5 ± 3.8 to 15.1 ± 4.1), A (50.0 ± 15.2 to 75.8 ± 18.2), A′ (8.1 ± 1.6 to 14.8 ± 5.9), S′ (8.7 ± 1.4 to 15.1 ± 4.5) and isovolumic acceleration (IVA) (104.2 ± 14.7 to 151.1 ± 20.6). In the CSCI group, only A (49.5 ± 9.9 to 56.9 ± 10.9) and IVA (94.4 ± 27.2 to 134.7 ± 27.7) showed a significant change. Conclusions: In the control group, heat stress increased left atrial contractility, left ventricular dilatation, and left ventricular contractility, while in patients with CSCI, left atrial contractility and left ventricular contractility improved, but there was no improvement in left ventricular diastolic function. This discrepancy in the impact of HHWI on cardiac function suggests that the sympathetic nervous system predominantly influences left ventricular dilatation during whole-body heat stress. However, other factors may also contribute to left atrial and ventricular contractility. Full article

Background and Objectives: Third molar (wisdom tooth) extraction is one of the most common surgical procedures in oral and maxillofacial surgery. Traditional rotary instruments and burs have long been the standard tools for this procedure. However, recent advancements in surgical techniques, such as piezoelectric surgery, have gained popularity due to their purported advantages in terms of precision, safety, and postoperative outcomes. This systematic review aims to evaluate the efficacy, safety, and clinical outcomes of third molar surgery performed using burs versus piezoelectric surgery. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using the PubMed, Scopus, Web of Science, and Cochrane databases to identify relevant studies published up until October 2024. Randomized controlled trials (RCTs), clinical trials, and comparative studies assessing third molar surgery using either burs or piezoelectric instruments were included. The primary outcomes evaluated were surgical time, postoperative pain, swelling, nerve damage, and healing time. The data extraction and quality assessment were performed independently by two reviewers using standardized tools, and any discrepancies were resolved by a third reviewer. Results: A total of five studies met the inclusion criteria, and the meta-analysis revealed that piezoelectric surgery resulted in significantly lower postoperative pain and swelling compared to traditional bur techniques (p < 0.05). Additionally, the incidence of nerve injury was lower in the piezoelectric group, though the difference was not statistically significant. Surgical time was found to be longer with piezoelectric devices, but this was offset by improved healing outcomes and patient comfort. Conclusions: Piezoelectric surgery offers a less traumatic alternative to traditional burs for third molar extraction, with reduced postoperative morbidity and enhanced patient outcomes. Although the longer surgical duration may be a drawback, the overall benefits, particularly in terms of pain management and tissue preservation, support the adoption of piezoelectric techniques in clinical practice. Further high-quality randomized trials are recommended to strengthen the evidence base for these findings. Full article