The morphological variability of the piriformis muscle.

BACKGROUND: The aim of the study is to create several classifications of the piriformis muscle (PM): proximal and distal attachments, potential fusions, and the relationship with the sciatic nerve. It is the first comprehensive anatomical examination of this subject. MATERIALS AND METHODS: One hundred and twenty-four lower limbs from 62 cadavers, fixed in 10% formalin, were examined. RESULTS: The piriformis muscle was present in 120 limbs (96.8% of cases). Four types of proximal attachment were described (I-IV). The most common type was Type I, in which the proximal attachment was at the anterior surface of the sacrum, between S2 and S4 (52 lower limbs; 43.3%). The rarest type was Type IV, in which the proximal attachment was at the gluteal surface of the ilium near the margin of the greater sciatic notch and from the gluteus medius (12 cases; 10%). Three types of distal attachment were distinguished. The most common was Type 1, a single tendon. This type comprised two subtypes: A and B (105 lower limbs; 87.5%). The other two types accounted for 12.5% of the total. Fusions were noted between the piriformis muscle and adjacent muscles in 31.7%. Four patterns were observed in which the sciatic nerve ran against the piriformis muscle. The most common variation in the relationship was the common fibular nerve exiting superior to the piriformis muscle and the tibial nerve passing inferior to it (10 cases; 8.3%). CONCLUSIONS: The piriformis muscle is highly morphologically variable in both its proximal and distal attachments and its relationship with the sciatic nerve. There are four types of proximal attachment and three types of distal attachment. The piriformis muscle shows numerous fusions with its adjacent muscles: gluteus medius or minimus or superior gemellus. A new (fourth) type of relationship was demonstrated between the piriformis muscle and sciatic nerve. The piriformis muscle was absent in four cases.

Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient.

Background: Neoplastic lesions affecting peripheral nerves are rare in the general population and, most often, are benign peripheral nerve sheath tumors. However, a minority of lesions represent high-grade malignancies associated with a poor prognosis, such as malignant peripheral nerve sheath tumors (MPNSTs). Very rarely, these tumors represent peripheral non-nerve sheath tumors (PNNSTs), such as hematological neoplasms that impair nerve function. These can be hard to distinguish from MPNSTs and other lesions arising from the nerve itself. In the present case report, we describe a rare case of direct infiltration of nerves by tumor cells of a hematological neoplasm. Methods: We report the case of a 90-year-old woman with acute onset of right-sided foot palsy, sensory loss, and pain, caused by an extensive solitary mass of the sciatic nerve in the thigh. We present and discuss the clinical presentation, multimodal diagnostic procedures, and treatment. Results: MRI of the right thigh and the caudal pelvis revealed a contrast-enhancing lesion infiltrating the sciatic nerve. Additionally performed staging imaging was non-revealing. After multidisciplinary discussion in the neuro-oncology tumor board, a MPNST was suspected and the patient underwent radical tumor resection. However, final histopathology revealed a diffuse large B-cell lymphoma (DLBCL). The patient received adjuvant palliative local radiotherapy which led to acceptable symptom control. Conclusion: Rare PNNSTs, including extranodal manifestations of DLBCL can have similar clinical and radiological diagnostical features as PNSTs. Comprehensive diagnostic workup of contrast-enhancing lesions affecting peripheral nerves including MRI and metabolic imaging are recommended. Discussion in interdisciplinary tumor boards facilitates finding individual treatment approaches.

MRI findings correlate with difficult dissection during proximal hamstring repair and with postoperative sciatica.

OBJECTIVE: This study examines the correlation between MRI findings and difficult dissection during proximal primary hamstring repair and postoperative sciatica. MATERIALS AND METHODS: A total of 32 cases of surgically repaired hamstring tendon tears that underwent preoperative and postoperative MRI were divided into sciatica (n = 12) and control (n = 20) groups based on the presence or absence of postoperative sciatica. Cases were scored by two blinded musculoskeletal radiologists for imaging features associated with difficult surgical dissection and the development of subsequent sciatica. Intra- and interrater agreements, as well as correlation of MRI findings with symptoms (odds ratio, OR), were calculated. RESULTS: On preoperative MRI, diffuse hamstring muscle edema pattern suggestive of active denervation (OR 9.4-13.6), and greater sciatic perineural scar circumference (OR 1.9-2) and length (OR 1.2-1.3) were significantly correlated with both difficult dissection and postoperative sciatica. Preoperatively, a greater number of tendons torn (OR 3.3), greater tear cross-sectional area (CSA, OR 1.03), and increased nerve T2-weighted signal (OR 3.2) and greater perineural scar thickness (OR 1.7) were also associated with difficult dissection, but not postoperative sciatica. On postoperative MRI, hamstring denervation, sciatic nerve tethering to the hamstring tendon, and development of perineural scar and greater perineural scar extent were all significantly correlated with postoperative sciatica. CONCLUSION: Preoperative hamstring MRI demonstrates findings predictive of difficult sciatic nerve dissection; careful MRI evaluation of the nerve and for the presence and extent of perineural scar is important for preoperative planning. Preoperative and postoperative MRI both depict findings that correlate with postoperative sciatica.

Innervation patterns of hamstring muscles, including morphological descriptions and clinical implication.

PURPOSE: The hamstrings muscles are innervated by sciatic nerve branches. However, previous studies assessing which and how many branches innervate each muscle have yielded discrepant results. This study investigated the innervation patterns of hamstrings. MATERIALS AND METHODS: Thirty-five cadaver limbs were investigated. The average age of subjects was 78.6 ± 17.2 years, with 48.6% male and 51.4% female, while 57.1% were right limbs and 42.9% left. The sciatic nerve, hamstrings and associated structures were dissected. The number of nerve branches for each muscle and the level where they penetrated the muscle were recorded. RESULTS: The sciatic nerve was connected by a fibrous band to the long head of the biceps femoris. This muscle was innervated by either one or two branches, which penetrated the muscle into its superior or middle third. The short head of the biceps femoris was innervated by a single nerve that usually penetrated its middle third, but sometimes inferiorly or, less commonly, superiorly. The semitendinosus was always innervated by two branches, the superior branch penetrating its upper third, the inferior mostly the middle third. The semimembranosus usually was innervated by a single nerve branch that penetrated the muscle at its middle or lower third. Four specimens revealed common nerves that innervated than one muscle. CONCLUSIONS: We have characterized hamstring innervation patterns, knowledge that is relevant to neurolysis, surgery of the thigh, and other procedures. Moreover, a mechanical connection between the sciatic nerve and biceps femoris long head was identified that could explain certain neuralgias.

The Association between Anatomical Variants of Musculoskeletal Structures and Nerve Compressions of the Lower Limb: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to describe the main anatomical variants and morphofunctional alterations in the lower limb that compress surrounding nervous structures in the gluteal region, thigh region, and leg and foot region. Methods: We searched the Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to October 2023. An assurance tool for anatomical studies (AQUA) was used to evaluate methodological quality, and the Joanna Briggs Institute assessment tool for case reports was also used. Forest plots were generated to assess the prevalence of variants of the gluteal region, thigh, and leg. Results: According to the forest plot of the gluteal region, the prevalence was 0.18 (0.14-0.23), with a heterogeneity of 93.52%. For the thigh region, the forest plot presented a prevalence of 0.10 (0.03-0.17) and a heterogeneity of 91.18%. The forest plot of the leg region was based on seven studies, which presented a prevalence of 0.01 (0.01-0.01) and a heterogeneity of 96.18%. Conclusions: This review and meta-analysis showed that, in studies that analyzed nerve compressions, the prevalence was low in the thigh and leg regions, while in the gluteal region, it was slightly higher. This is mainly due to the PM region and its different variants. We believe that it is important to analyze all the variant regions defined in this study and that surgeons treating the lower limb should be attentive to these possible scenarios so that they can anticipate possible surgical situations and thus avoid surgical complications.

Ultrasound-Guided Sciatic Nerve Hydrodissection Can Improve the Clinical Outcomes of Patients with Deep Gluteal Syndrome: A Case-Series Study.

Deep gluteal syndrome (DGS) is caused by sciatic nerve entrapment. Because fascial entrapment neuropathies may occur in multiple locations, ultrasound-guided nerve hydrodissection is a key component of DGS treatment. In this study, we examined the clinical outcomes of patients with DGS undergoing ultrasound-guided sciatic nerve hydrodissection. A 10 mL mixture consisting of 5% dextrose, 0.2% lidocaine (Xylocaine), and 4 mg betamethasone (Rinderon) was used for nerve hydrodissection. Clinical outcomes were evaluated using Numeric Rating Scale (NRS) scores of pain, the proportion of patients with favorable outcomes (reduction of ≥50% in pain), the duration for which patients exhibited favorable outcomes (percentage of follow-up duration), and the occurrence of major complications and minor side effects. A total of 53 patients were consecutively included and followed up for 3 to 19 months. After the initial injection, the NRS scores significantly improved at 1 week, 1 month, 3 months, and the final follow-up. Specifically, 73.6%, 71.7%, 64.2%, and 62.3% of the patients exhibited favorable outcomes at 1 week, 1 month, 3 months, and the final follow-up, respectively. The median duration for which the patients exhibited favorable outcomes was 84.7% of the follow-up period. Three patients (5.7%) experienced transient dizziness and vomiting, which resolved without further treatment. No vessel or nerve puncture was observed. Overall, ultrasound-guided sciatic nerve hydrodissection is a safe procedure that mitigates the pain associated with DGS. To achieve favorable outcomes, three consecutive injections 3 weeks apart are required.

Similar incidence of postoperative sciatic nerve palsy in direct anterior and posterior approach total hip arthroplasty.

BACKGROUND: Sciatic nerve palsy is a rare but devastating complication following total hip arthroplasty (THA). While the use of the direct anterior approach is increasing, limited data exist regarding sciatic nerve palsy and surgical approach. The purpose of this study was to determine the factors and outcomes associated with sciatic nerve palsy (SNP) after THA. METHODS: A retrospective analysis was performed at a single institution of 7 SNP that occurred in 4045 THA via direct anterior approach and 10 SNP in 8854 THA via posterior approach, being operated between 01 January 2017 and 12 December 2021. SNP patients were matched 1:5 to patients without SNP. Medical records were reviewed for demographics including age, gender, body mass index (BMI), comorbidities, and preoperative indication. Additional workup of SNP patients including advanced imaging and reoperation were documented. Recovery grades were assigned to all SNP patients at most recent clinical follow-up. RESULTS: 5 of the SNP were complete and 12 partial. They occurred as frequently with the direct anterior (0.17%) and posterior approach (0.11%, p = 0.5). The presence of femur cables and reoperations were associated with SNP (p = 0.04 and p = 0.002, respecitvely). Age, gender, BMI, comorbidities, and surgical indication had no effect on SNP. 4 of the 17 affected patients had almost complete recovery at latest follow-up. CONCLUSIONS: The incidence of SNP was similar in direct anterior and posterior approach. Surgeons should counsel patients regarding the risks of SNP regardless of the used approach.

A Bilateral Symmetrical Variant Formation of the Sural Nerve.

Typically, the sural nerve is formatted by the connection of the lateral sural cutaneous nerve (branch of the common fibular nerve) and the medial sural cutaneous nerve (branch of the tibial nerve). The current cadaveric report aims to describe a quite unusual symmetrical variant of the sural nerve. Classical dissection was performed on an 84-year-old donated male cadaver. On both sides, the sural nerve was formatted directly by the sciatic nerve. After its emanation, it continued its typical course between the gastrocnemius muscle heads. Sural nerve formation has been extensively studied due to its great clinical significance. The identified variant corresponds to one of the rarest types of sural nerve formation. Knowledge of sural nerve variants may play a crucial role in lower limb surgery and nerve harvest for reconstruction.

Foreign substance injection for esthetic purposes associated with delayed unilateral sciatic nerve impairment: A surgical case report.

Attempts at body contour modifications have led to the use of different alloplastic materials that can irreversibly damage health and risk patients' lives. These modeling substances can induce a general autoimmune inflammatory response, producing a very heterogeneous clinical spectrum ranging from mild and severe systemic to local symptoms that sometimes affect peripheral nerves. We report a unique case of a tumor-like sciatic nerve impairment produced months after the injection of a modeling substance into the buttocks for esthetic purposes. The patient was treated with a surgical decompression of the sciatic nerve that encompassed the removal of the injected mass. This approach ultimately yielded a complete neurological recovery of the affected nerve. We emphasize the diagnostic approach and surgical management employed in this unique case and review the current literature on this infrequent complication.

Concomitant treatment of ureteral calculi and ipsilateral pelvic sciatic nerve schwannoma with transperitoneal laparoscopic approach: A case report.

BACKGROUND: Schwannomas are rare peripheral neural myelin sheath tumors that originate from Schwann cells. Of the different types of schwannomas, pelvic sciatic nerve schwannoma is extremely rare. Definite preoperative diagnosis of pelvic schwannomas is difficult, and surgical resection is the gold standard for its definite diagnosis and treatment. CASE SUMMARY: We present a case of pelvic schwannoma arising from the sciatic nerve that was detected in a 40-year-old man who underwent computed tomography for intermittent right lower back pain caused exclusively by a right ureteral calculus. Subsequently, successful transperitoneal laparoscopic surgery was performed for the intact removal of the stone and en bloc resection of the schwannoma. The total operative time was 125 min, and the estimated blood loss was inconspicuous. The surgical procedure was uneventful. The patient was discharged on postoperative day 5 with the simultaneous removal of the urinary catheter. However, the patient presented with motor and sensory disorders of the right lower limb, caused by partial damage to the right sciatic nerve. No tumor recurrence was observed at the postoperative appointment. CONCLUSION: Histopathological examination of the specimen confirmed the diagnosis of a schwannoma. Thus, laparoscopic surgery is safe and feasible for concomitant extirpation of pelvic schwannomas and other pelvic and abdominal diseases that require surgical treatment.

Dexamethasone versus Dexmedetomidine as Adjuvants in Ultrasound Popliteal Sciatic Nerve Block for Hallux Valgus Surgery: A Mono-Centric Retrospective Comparative Study.

Background and Aim: Ultrasound popliteal sciatic nerve block (UPSNB) is commonly performed in foot and ankle surgery. This study aims to assess the use of dexmedetomidine and dexamethasone as adjuvants in UPSNB for hallux valgus (HV) surgery, comparing their efficacy in producing motor and sensory block and controlling postoperative pain. The adverse event rate was also evaluated. Methods: This mono-centric retrospective study included 62 adult patients undergoing HV surgery: 30 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg and dexamethasone 4 mg (Group 1), whereas 32 patients received lidocaine 2% 200 mg, ropivacaine 0.5% 50 mg, and dexmedetomidine 1 mcg/Kg (Group 2). At first, the visual analogue scale (VAS) was evaluated after 48 hours. The other outcomes were time to motor block regression, evaluation of the first analgesic drug intake, analgesic effect, adverse effects (hemodynamic disorders, postoperative nausea and vomiting (PONV)) and patient satisfaction. The continuous data were analyzed with student's t-test and the continuous one with χ2. Statistical significance was set at a p-value lower than 0.05. Results: No significant difference was found in VAS after 48 hours (4.5 ± 1.6 vs 4.7 ± 1.7, p = 0.621) to motor block regression (18.9 ± 6.0 vs 18.7 ± 6, p = 0.922). The number of patients that took their first analgesic drug in the first 48 h (p = 0.947 at 6 hours; p = 0.421 at 12 hours; p = 0.122 at 24 hours and p = 0.333 at 48 hours) were not significant. A low and similar incidence of intraoperative hemodynamic disorders was recorded in both groups (hypotension p = 0.593; bradycardia p = 0.881). Neither PONV nor other complication was found. Patients in Group 1 reported a lower degree of interference with sleep (p = 0.001), less interference with daily activities (P = 0.002) and with the affective sphere (P = 0.015) along with a more satisfactory postoperative pain management (p < 0.001) as compared to Group 2. Conclusion: No significant differences were observed in the duration of motor and sensory blockade between patients in both groups. Additionally, both groups showed good pain control with a low rate of adverse effects, even if there was no clinical difference between the groups. However, patients who received dexamethasone reported experiencing less interference with their sleep, daily activities and overall emotional well-being, and overall pain control.

Bone marrow stromal cell-conditioned medium regenerates injured sciatic nerve by increasing expression of MPZ and NGF and decreasing apoptosis.

Objectives: Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

Deep Gluteal syndrome: An underestimated cause of posterior hip pain.

Deep gluteal syndrome (DGS) is a significant cause of posterior hip pain resulting from the compression of the sciatic or other peripheral nerves in the deep gluteal space. Understanding the anatomy of the deep gluteal space and the kinematics of the sciatic nerve, as it passes through this region is crucial for understanding DGS. Despite increasing awareness, DGS is still often overlooked. This review focuses on conditions that specifically contribute to posterior hip pain as a consequence of DGS. Predominantly addressing piriformis syndrome, gemelli-obturator internus syndrome, ischiofemoral impingement syndrome, and proximal hamstring syndrome, the review also touches upon rare cases such as inferior and superior gluteal nerve entrapment.

Inhibition of compound action potentials in the frog sciatic nerve by inchinkoto, a traditional Japanese medicine used for oral mucositis.

OBJECTIVE: This study aimed to determine the effects of traditional Japanese (Kampo) medicines used to treat oral mucositis on nerve conduction. METHODS: The effects of Kampo medicines, crude drugs, and chemical compounds on compound action potentials (CAPs) were analyzed using extracellular recordings in frog sciatic nerves. RESULTS: Among the Kampo medicines, inchinkoto demonstrated the most significant reduction in CAP amplitude, with a half-maximal inhibitory concentration (IC50) of 5.4 mg/mL. Hangeshashinto, shosaikoto, hochuekkito, and juzentaihoto also showed a significant reduction. Regarding inchinkoto, Artemisiae Capillari Spica (artemisia) was the most effective crude drug, with an IC50 of 4.2 mg/mL for CAP amplitude reduction, whereas Gardeniae Fructus (gardenia) exerted no significant effect. However, the combined use of artemisia and gardenia reduced the CAP amplitude more effectively than artemisia alone, indicating a synergistic interaction. The chemical ingredient eugenol from artemisia administered at 1 and 3 mmol/L reduced CAP amplitude, whereas other chemical ingredients administered at 0.1 and 1 mmol/L had no significant effects. CONCLUSIONS: Inchinkoto exhibited the most effective reduction in CAP amplitude in the sciatic nerve of frogs, primarily through the action of artemisia, with potential synergistic interaction between artemisia and gardenia.

Skeletal muscle atrophy after sciatic nerve damage: Mechanistic insights.

Sciatic nerve injury leads to molecular events that cause muscular dysfunction advancement in atrophic conditions. Nerve damage renders muscles permanently relaxed which elevates intracellular resting Ca2+ levels. Increased Ca2+ levels are associated with several cellular signaling pathways including AMPK, cGMP, PLC-ß, CERB, and calcineurin. Also, multiple enzymes involved in the tricarboxylic acid cycle and oxidative phosphorylation are activated by Ca2+ influx into mitochondria during muscle contraction, to meet increased ATP demand. Nerve damage induces mitophagy and skeletal muscle atrophy through increased sensitivity to Ca2+-induced opening of the permeability transition pore (PTP) in mitochondria attributed to Ca2+, ROS, and AMPK overload in muscle. Activated AMPK interacts negatively with Akt/mTOR is a highly prevalent and well-described central pathway for anabolic processes. Over the decade several reports indicate abnormal behavior of signaling machinery involved in denervation-induced muscle loss but end up with some controversial outcomes. Therefore, understanding how the synthesis and inhibitory stimuli interact with cellular signaling to control muscle mass and morphology may lead to new pharmacological insights toward understanding the underlying mechanism of muscle loss after sciatic nerve damage. Hence, the present review summarizes the existing literature on denervation-induced muscle atrophy to evaluate the regulation and expression of differential regulators during sciatic damage.

Cell Heterogeneity and Variability in Peripheral Nerve after Injury.

With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been extensively studied, the cellular composition of the peripheral nerve has gradually been revealed. By summarizing the current sequencing data, we compile the heterogeneities of cells that have been reported in the peripheral nerves, mainly the sciatic nerve. The cellular variability of Schwann cells, fibroblasts, immune cells, and endothelial cells during development and disease has been discussed in this review. The discovery of the architecture of peripheral nerves after injury benefits the understanding of cellular complexity in the nervous system, as well as the construction of tissue engineering nerves for nerve repair and axon regeneration.

Transcriptomic profiling of sciatic nerves and dorsal root ganglia reveals site-specific effects of prediabetic neuropathy.

Peripheral neuropathy (PN) is a severe and frequent complication of obesity, prediabetes, and type 2 diabetes characterized by progressive distal-to-proximal peripheral nerve degeneration. However, a comprehensive understanding of the mechanisms underlying PN, and whether these mechanisms change during PN progression, is currently lacking. Here, gene expression data were obtained from distal (sciatic nerve; SCN) and proximal (dorsal root ganglia; DRG) injury sites of a high-fat diet (HFD)-induced mouse model of obesity/prediabetes at early and late disease stages. Self-organizing map and differentially expressed gene analyses followed by pathway enrichment analysis identified genes and pathways altered across disease stage and injury site. Pathways related to immune response, inflammation, and glucose and lipid metabolism were consistently dysregulated with HFD-induced PN, irrespective of injury site. However, regulation of oxidative stress was unique to the SCN while dysregulated Hippo and Notch signaling were only observed in the DRG. The role of the immune system and inflammation in disease progression was supported by an increase in the percentage of immune cells in the SCN with PN progression. Finally, when comparing these data to transcriptomic signatures from human patients with PN, we observed conserved pathways related to metabolic dysregulation across species, highlighting the translational relevance of our mouse data. Our findings demonstrate that PN is associated with distinct site-specific molecular re-programming in the peripheral nervous system, identifying novel, clinically relevant therapeutic targets.

Disturbed brain energy metabolism in a rodent model of DYT-TOR1A dystonia.

DYT-TOR1A (DYT1) dystonia, characterized by reduced penetrance and suspected environmental triggers, is explored using a "second hit" DYT-TOR1A rat model. We aim to investigate the biological mechanisms driving the conversion into a dystonic phenotype, focusing on the striatum's role in dystonia pathophysiology. Sciatic nerve crush injury was induced in ∆ETorA rats, lacking spontaneous motor abnormalities, and wild-type (wt) rats. Twelve weeks post-injury, unbiased RNA-sequencing was performed on the striatum to identify differentially expressed genes (DEGs) and pathways. Fenofibrate, a PPARα agonist, was introduced to assess its effects on gene expression. 18F-FDG autoradiography explored metabolic alterations in brain networks. Low transcriptomic variability existed between naïve wt and ∆ETorA rats (17 DEGs). Sciatic nerve injury significantly impacted ∆ETorA rats (1009 DEGs) compared to wt rats (216 DEGs). Pathway analyses revealed disruptions in energy metabolism, specifically in fatty acid ß-oxidation and glucose metabolism. Fenofibrate induced gene expression changes in wt rats but failed in ∆ETorA rats. Fenofibrate increased dystonia-like movements in wt rats but reduced them in ∆ETorA rats. 18F-FDG autoradiography indicated modified glucose metabolism in motor and somatosensory cortices and striatum in both ∆ETorA and wt rats post-injury. Our findings highlight perturbed energy metabolism pathways in DYT-TOR1A dystonia, emphasizing compromised PPARα agonist efficacy in the striatum. Furthermore, we identify impaired glucose metabolism in the brain network, suggesting a potential shift in energy substrate utilization in dystonic DYT-TOR1A rats. These results contribute to understanding the pathophysiology and potential therapeutic targets for DYT-TOR1A dystonia.

Development and validation of an LC-MS/MS method for quantifying NAD+ and related metabolites in mice sciatic nerves and its application to a nerve injury animal model.

Recent studies highlight the pivotal roles of Nicotinamide adenine dinucleotide (NAD+) and its metabolites in aging and neurodegeneration. Accurate quantification of NAD+ and its metabolite levels in cells or tissues is crucial for advancing biochemical research and interventions targeting aging and neurodegenerative diseases. This study presents an accurate, precise, and rapid LC-MS/MS method using a surrogate matrix to quantify endogenous substances NAD+, nicotinamide mononucleotide (NMN), nicotinamide (NAM), adenosine diphosphate ribose (ADPR), and cyclic adenosine diphosphate ribose (cADPR) concentrations in mice sciatic nerves. Considering the properties of the phosphate groups in the analytes, the column and mobile phase were systematically optimized. These five polar analytes exhibited excellent analytical performance and baseline separation within 5 min on an Atlantis Premier BEH C18 AX column, with methylene phosphonic acid as a mobile phase additive. Enhanced sensitivity addressed the challenges posed by the small sample size of mice sciatic nerve and low NMN and cADPR detection. The method was fully validated, with linear correlation coefficients exceeding 0.992, precision (%relative standard deviation, RSD) values within 8.8%, and accuracy values between 92.2% and 107.3%, suggesting good reproducibility. Analytical recoveries in spiked and diluted matrix ranged from 87.8% to 104.7%, indicating the suitability of water as a surrogate matrix. Application of the method to quantify NAD+ and its metabolite levels in normal and injured mice sciatic nerve identified cADPR as a sensitive biomarker in the nerve injury model. This method is anticipated to deepen our understanding of the connections between NAD+ and its metabolites in health and disease, potentially improving diagnoses of various neurological disorders and aiding drug development for aging and neurodegenerative diseases.

Development of new nanofibrous nerve conduits by PCL-Chitosan-Hyaluronic acid containing Piracetam-Vitamin B12 for sciatic nerve: A rat model.

Peripheral nerve injury is a critical condition that can disrupt nerve functions. Despite the progress in engineering artificial nerve guidance conduits (NGCs), nerve regeneration remains challenging. Here, we developed new nanofibrous NGCs using polycaprolactone (PCL) and chitosan (CH) containing piracetam (PIR)/vitamin B12(VITB12) with an electrospinning method. The lumen of NGCs was coated by hyaluronic acid (HA) to promote regeneration in sciatic nerve injury. The NGCs were characterized via Scanning Electron Microscopy (SEM), Fourier transform infrared (FTIR), tensile, swelling, contact angle, degradation, and drug release tests. Neuronal precursor cell line (PCL12 cell) and rat mesenchymal stem cells derived from bone marrow (MSCs) were seeded on the nanofibrous conduits. After that, the biocompatibility of the NGCs was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, and SEM images. The SEM demonstrated that PCL/CH/PIR/VITB12 NGCs had nonaligned, interconnected, smooth fibers. The mechanical properties of these NGCs were similar to rat sciatic nerve. These conduits had an appropriate swelling and degradation rate. The In Vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VITB12 NGCs towards PC12 cells and MSCs. The in vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VIT B12 NGCs towards MSCs and PC12 cells. To analyze functional efficacy, NGCs were implanted into a 10 mm Wistar rat sciatic nerve gap and bridged the proximal and distal stump of the defect. After three months, the results of sciatic functional index (55.3 ± 1.8), hot plate latency test (5.6 ± 0.5 s), gastrocnemius muscle wet weight-loss (38.57 ± 1.6 %) and histopathological examination using hematoxylin-eosin (H&E) /toluidine blue/ Anti-Neurofilament (NF200) staining demonstrated that the produced conduit recovered motor and sensory functions and had comparable nerve regeneration compared to the autograft that can be as the gold standard to bridge the nerve gaps.