Search Results (289)

Trigeminal neuralgia and orofacial pain often require effective local anesthesia with minimal side effects. Puerarin (PUE), a major bioactive flavonoid derived from Pueraria lobata, has shown potential analgesic properties. This study aimed to investigate the inhibitory effects of local PUE administration on the excitability of wide-dynamic-range (WDR) neurons in the spinal trigeminal nucleus caudalis (SpVc) and to compare its potency with the conventional local anesthetic lidocaine. Extracellular single-unit recordings were performed on SpVc WDR neurons in anesthetized rats. PUE (1 and 10 mM) or lidocaine (37 mM; 1%) was administered subcutaneously into the peripheral receptive field. Neuronal responses to graded non-noxious and noxious mechanical stimuli were quantified before and after drug application. Local administration of PUE significantly suppressed the mean firing frequency of SpVc WDR neurons in a dose-dependent and reversible manner. The inhibitory effect peaked at 10 min post-injection and recovered within 30 min. Notably, 10 mM PUE exerted an inhibitory magnitude (68.7 ± 6.4%) comparable to that of 37 mM lidocaine (58.1 ± 4.3%), indicating that PUE possesses approximately four-fold the inhibitory potency of lidocaine on a molar basis. The suppressive effect was consistent across both non-noxious and noxious stimulus intensities. These findings provide the first in vivo evidence that PUE effectively attenuates trigeminal nociceptive transmission, likely via the modulation of voltage-gated sodium channels and acid-sensing ionic channels at peripheral nerve terminals. As a natural dietary constituent with high potency and a low risk of systemic side effects, PUR represents a promising candidate for complementary and alternative medicine in the management of orofacial pain, such as temporomandibular disorders and trigeminal neuralgia. Full article

Glycolysis-derived pyruvate is the almost exclusive source of acetyl-CoA for energy production in mitochondrial compartments of all types of neuronal and glial cells. Neurons utilize several times more glucose than glial cells due to their neurotransmitter functions. Cholinergic neurons that are responsible for cognitive functions require additional amounts of acetyl-CoA for acetylcholine-transmitter synthesis in their cytoplasmic compartment. It may be assured by preferential localization of ATP-citrate lyase (ACLY) in the cytoplasm of cholinergic neurons’ perikaryons and axonal terminals. This thesis is supported by the existence of strong regional and developmental correlations of ATP-citrate lyase and choline acetyltransferase (ChAT) activities and ACh levels in the brain. Electrolytic or chemical lesions of cholinergic nuclei cause proportional loss of the above parameters in the respective cortical target areas. On the other hand, the regional activity of mitochondrial pyruvate dehydrogenase complex (PDHC), which synthesizes nearly the whole pool of neuronal acetyl-CoA, displays no correlation with cholinergic innervation. It makes cholinergic neurons highly susceptible to brain pathologies impairing energy metabolism. Therefore, the ACLY pathway, which provides acetyl units directly to the site of acetylcholine synthesis in cholinergic nerve terminals, plays a key role in the maintenance of cholinergic neurotransmission. On the other hand, in cholinergic motor neurons, various ACLY–protein complexes are involved not only in neurotransmission but also in axonal transport of cholinergic elements from the perikaryon to cholinergic neuro-muscular junctions. This review presents findings supporting this thesis. Full article

Background: The pterygomaxillary region is a complex anatomical area formed by the junction of the maxillary, palatine, and sphenoid bones and contains critical neurovascular structures. Accurate assessment of this region during Le Fort I osteotomy is essential, particularly to prevent hemorrhage and nerve injury that may occur during the pterygomaxillary separation phase. This study aims to investigate the morphometric characteristics of the pterygomaxillary region using cone-beam computed tomography (CBCT) and to evaluate the effects of age, sex, and laterality on these anatomical parameters. Materials and Methods: In this retrospective study, CBCT scans of 200 individuals (100 males and 100 females) aged 20–80 years were analyzed. Axial measurements included distances between the piriform rim, the descending palatine artery, the pterygomaxillary osteotomy line, and the pterygomaxillary fissure. Additionally, the thickness and width of the pterygomaxillary region and pterygoid process, lengths of the medial and lateral pterygoid laminae, and the distance between the greater palatine canal and the medial pterygoid lamina apex were recorded. Measurements were statistically evaluated by sex, age group, and laterality. Results: The following parameters demonstrated statistically significant differences based on the conducted measurements: The distance between the piriform rim and the descending palatine artery was significantly greater on the left side (p < 0.001). The length of the lateral pterygoid lamina increased with advancing age (p = 0.048). The thickness of the pterygomaxillary region was significantly greater in females (p = 0.014). Additionally, the distance between the greater palatine canal and the terminal point of the medial pterygoid lamina was significantly higher in males (p < 0.001). Conclusions: The pterygomaxillary region exhibits anatomical variations that may lead to serious complications during Le Fort I osteotomy. Detailed preoperative evaluation of this area using CBCT can guide surgical planning and help prevent potential vascular and neural complications. Full article

Background: The rostral ventromedial medulla (RVM) is a central hub of the descending pain modulatory system, yet the inhibitory circuits that regulate its activity during neuropathic pain remain poorly defined. The zona incerta (ZI), a predominantly GABAergic nucleus in the subthalamic region, has been implicated in nociceptive modulation, but its functional connection to the RVM has not been established. Methods: A chronic constriction injury (CCI) model was used to induce neuropathic pain. Neuronal activation and circuit connectivity were examined using anatomical tracing and activity mapping. Optogenetic and chemogenetic approaches were employed to selectively manipulate ZI-derived GABAergic projections to the RVM, and mechanical sensitivity was assessed using behavioral assays. Results: CCI selectively activated ZI neurons on the ipsilateral side of nerve injury (p = 0.0452), which projected to the ipsilateral RVM. Optogenetic activation of ZI-derived terminals in the RVM significantly alleviated CCI-induced mechanical allodynia (p = 0.0038), whereas optogenetic inhibition exacerbated pain behaviors (p = 0.0183). Consistently, chemogenetic excitation of ZI–RVM neurons attenuated hypersensitivity (p < 0.0001), while chemogenetic silencing had the opposite effect (p = 0.0015). Conclusions: These findings reveal a novel diencephalic-to-brainstem inhibitory pathway that exerts dynamic control over RVM-mediated descending modulation of neuropathic pain. Full article

Background and Objectives: The masseteric artery (Ma) enters the masseter muscle (Mm) together with the masseteric nerve (Mn) via the mandibular notch. Morphological detail on the intramuscular course of the Ma and its relationship to the Mn remains scarce to date. When utilizing the Mn in facial reanimation surgery, a constant relationship between the Ma and Mn could be used for intramuscular orientation when preparing the Mn and for an indirect localization via ultrasound. This study examines the intramuscular course of the Ma and its relationship to the Mn. Materials and Methods: Sixty hemicrania obtained from thirty postmortem individuals aged between 54 and 99 years and embalmed using the Thiel methods were examined. Results: Four types of Ma were identified according to their endpoint in the Mm. In 5% of cases, no Ma could be identified (Type 0), 48.3% (Type 1) terminated within the upper third, 41.7% (Type 2) in the middle third, and 5% (Type 3) in the lower third. The Ma consistently entered the Mm inferior and in 85% of cases additionally slightly posterior to the Mn. The main trunk of the Ma crossed the Mn in the upper third of the Mm in 31.7% of cases, in the middle third in 23.3%, and in the lower third in 1.7% of cases. Of these, 13.3% had the Ma crossing the Mn. Smaller branches crossed the Mn in 45% of cases. Conclusions: If an Ma is present, it may be used for intramuscular orientation and indirect location of the Mn via the mandibular notch. Since the Ma reaches the lower third of the muscle in only a few cases, it is unsuitable for intramuscular orientation to locate the Mn via a distal approach. Full article

Skeletal muscle atrophy underlies sarcopenia, frailty, and muscular dystrophies, but the molecular mechanisms linking oxidative stress to muscle degeneration remain incompletely understood. We previously identified protein complex formation between transient receptor potential canonical 3 (TRPC3) and NADPH oxidase 2 (Nox2) as a key driver of anthracycline-induced myocardial atrophy. Here, we investigated whether this complex also contributes to skeletal muscle wasting. In skeletal muscle from sciatic nerve transection model mice and Duchenne muscular dystrophy (mdx) mice, TRPC3-Nox2 complex formation was enhanced. TRPC3 deletion significantly attenuated denervation-induced soleus atrophy and reduced reactive oxygen species (ROS) production. TRPC3-Nox2 complex formation was upregulated in the soleus muscle (SM) of mdx mice. Pharmacological disruption of the TRPC3-Nox2 interaction improved muscle size and strength and reduced plasma creatine kinase in mdx mice. A recombinant adeno-associated virus (AAV) encoding a TRPC3 C-terminal peptide was used to suppress TRPC3-Nox2 complex formation in vivo. AAV-mediated expression of TRPC3 C-terminal peptide mitigated muscle wasting (CSA) in mdx mice, while muscle strength and plasma CK were not significantly improved. Thus, TRPC3-Nox2 complex formation may be a pivotal driver of oxidative stress-mediated skeletal muscle atrophy. Targeting this protein–protein interaction represents a promising therapeutic strategy for Duchenne muscular dystrophy (DMD) and other intractable muscle-wasting disorders. Full article

Background/Objectives: The neurotransmitter glycine is involved in several physiological and pathological conditions in the Central Nervous System. Different biological structures, including glycine receptors and transporters, are under study as targets for potential drugs acting against serious neurological and psychiatric disorders. The regulation of glycine release from nerve terminals is only partially understood. We report here preliminary evidence of the modulation of glycine release through presynaptic metabotropic glutamate receptors 1 (mGlu1) from glycinergic nerve terminals in mouse hippocampi. Methods: Purified mouse hippocampal synaptosomes labeled with [³H]glycine were used to study glycine release under superfusion conditions. Results: The group I metabotropic glutamate receptor agonist 3,5-DHPG potentiated depolarization-evoked [³H]glycine release from hippocampal synaptosomes, an effect strongly counteracted by the selective mGlu1 antagonist LY 367385. 3,5-DHPG failed to increase [³H]glycine release in Grm1^crv4/crv4 mice, a mouse model lacking mGlu1. Although further research is needed to clarify these mechanisms, data suggest that glycine-releasing hippocampal nerve terminals are endowed with presynaptic mGlu1 receptors whose activation potentiates glycine release. Conclusions: Considering that in the hippocampus, glycine is relevant as a co-agonist of glutamate at NMDA receptors and that mGlu1 receptor ligands are under study as potential drugs, we propose that the possible effects of these agents on the release of glycine should be considered when studying these compounds. Full article

The role of LAP proteins expressed in skeletal muscles (ERBIN, LANO, and SCRIBBLE) and at neuromuscular junctions (NMJs) remains largely unknown. Our previous data demonstrate that LAP proteins are differentially expressed in muscle cells, nerve endings, and terminal Schwann cells, though they are all expressed in myofibers and accumulate at NMJs. ERBIN and SCRIBBLE align with acetylcholine receptor clusters (CHRNs) at the NMJ. In vivo ablation of Erbin is associated with smaller CHRN and upregulation of Lano and Scribble. However, SCRIBBLE was also shown to influence the fate decision of muscle stem cells. Here, we investigated how the absence of SCRIBBLE in skeletal muscle cells might impair skeletal muscle fibers or NMJs. Although conditional Scribble knockout mice did not exhibit changes in weight or viability, force per weight decreased slightly. This was supported by compromised neuromuscular transmission and increased NMJ fragmentation. Moreover, Scribble knockout muscles transcribe less myosin heavy chain genes. Here, we also showed that RAB5, an effector of endocytic recycling, interacts with all LAP proteins, but in Scribble knockout muscles, reduced interaction was detected with ERBIN and LANO. These data suggest that a delicate signaling network employing LAP proteins is necessary for skeletal muscle fibers and NMJs. Full article

Background: Rabies virus (RABV) causes approximately 59,000 human deaths annually. Current pre- and post-exposure vaccination relies on inactivated vaccines (INVs) with limited yield and immunogenicity. We engineered a dual-cationic LNP-based nucleocapsid-like nanostructure (NLS) that co-encapsulates RABV G-mRNA and recombinant RABV-N to engage MHC-I/II pathways and enhance protection. Methods: A pVAX-RABV-G plasmid containing 5′/3′UTRs, Kozak, and poly(A) was transcribed in vitro. RABV-N with an N-terminal 6× His tag was expressed in E. coli BL21(DE3) and purified by Ni-Sepharose affinity chromatography. Dual-cationic LNPs (DHA, DOTAP Cl, mPEG-DTA2K, DOPC) were formulated by microfluidics at a 4:1 (G-mRNA:RABV-N) mass ratio. Vaccine quality was assessed by encapsulation efficiency, DLS, PDI, zeta potential, and TEM. Mice received empty LNPs, INV, G-mRNA, or NLS under varied schedules and doses. ELISA measured RABV-G/N-IgG; RFFIT determined neutralizing antibody (nAb) titers; ELISPOT quantified CTL response; qPCR assessed T-cell activation genes. On day 35 after the first immunization of vaccines, mice were challenged intramuscularly with 25 LD₅₀ of CVS-24. Results: G-mRNA purity was >95% and drove strong RABV-G expression in 293T cells. Purified RABV-N was approximately 52 kDa, >90% pure, and reactive to anti-His and anti-N antibodies. NLS achieved >95% encapsulation, a diameter of 136.9 nm, PDI 0.09, and a +18.7 mV zeta potential. A single dose yielded approximately 10 IU mL⁻¹ nAb by day 7; two doses peaked at approximately 1000 IU mL⁻¹. Mice showed 100% survival and no viral rebound in brain, spinal cord, and sciatic nerve. NLS induced stronger MHC-I/II-linked cellular immunity and higher RABV G/N-specific IFN-γ spot frequencies than G-mRNA or INV. Conclusions: The dual-antigen NLS vaccine co-delivering G-mRNA and RABV-N via dual-cationic LNPs robustly activates MHC-I/II, rapidly generates high-titer nAb (≥10 IU mL⁻¹ within 1 week), and sustains potent CD8⁺ CTL and CD4⁺ Th responses. A two-dose regimen (days 0 and 21) conferred complete protection, supporting the NLS platform as a next-generation rabies vaccine candidate. Full article

Background Facial clefts are rare congenital malformations, occurring in approximately 1 in 700 live births for cleft lip and palate and fewer than 1 in 100,000 for atypical Tessier clefts. They pose significant diagnostic and surgical challenges. While genetic, vascular, and environmental factors are well documented, growing embryological evidence suggests that the trigeminal nerve may also contribute to craniofacial development. This narrative review explores the association between trigeminal nerve development and facial clefts, aiming to provide a neurodevelopmental perspective with clinical implications, particularly in the context of personalized medicine, where patient-specific neuroanatomical and developmental factors can guide tailored care. Methods A narrative review of embryological, anatomical, and clinical data was conducted. Histological analyses of malformed fetuses and normal human embryos were integrated with published studies. Clinical findings were compared with Paul Tessier’s facial cleft classification and mapped against trigeminal innervation territories. Results Two groups of facial clefts emerged according to the timing of trigeminal disruption. Early embryonic damage (before 10 weeks of gestation) produces superficial epidermal continuity with fibrotic tissue replacing normal deep structures. Later fetal damage results in complete clefts with full tissue discontinuity. The distribution of these clefts corresponds to trigeminal nerve terminal branch territories, supporting the hypothesis that trigeminal innervation exerts trophic effects on craniofacial morphogenesis through neurohormonal signaling. Conclusions Early impairment of trigeminal development may play a pivotal role in the pathogenesis of certain clefts. The spatial and temporal relationship between nerve development and morphogenesis should be considered in classification and surgical planning. However, limitations of this narrative approach include selective literature coverage and lack of quantitative synthesis. Future directions include single-cell transcriptomics, organoid models, and fetal MRI tractography to clarify trigeminal–mesenchyme interactions and inform therapeutic strategies. These advances may foster a personalized medicine approach, enabling more precise prenatal diagnosis, individualized surgical planning, and optimized long-term outcomes. Full article

TRPV4 (transient receptor potential vanilloid 4) is a non-selective, multifunctional cationic channel that is expressed in numerous cells in the body. It can be activated by temperature, mechanical forces, and chemical and biochemical molecules. Functionally, TRPV4 participates in maintaining osmotic homeostasis, blood pressure, and hypoxic preconditioning. As far as we know, the presence of TRPV4 has never been reported in the carotid body despite the overlap that exists between some biological functions of TRPV4 and the physiology of the carotid body. In the present work, immunofluorescence associated with confocal laser microscopy, associated with quantitative analysis (area occupied by immunofluorescence), has been used to examine the occurrence of TRPV4 in the human carotid body. The results demonstrated the presence of TRPV4 in a subpopulation of chemoreceptor type I cells (approximately 65–68%), a subpopulation of type II supporting cells, and in nerve terminals in the human carotid body. Its function, if any, in this multisensory organ must be demonstrated, but it is in line with the functions attributed to the carotid body. Full article

The carotid body is a peripheral chemoreceptor that consists of clusters of chemoreceptive type I cells, glia-like type II cells, afferent and efferent nerves, and sinusoidal capillaries and arterioles. Cells and nerves communicate through reciprocal chemical synapses and electrical coupling that form a “tripartite synapse,” which allows for the process of sensory stimuli within the carotid body involving neurotransmission, autocrine, and paracrine pathways. In this network there are a variety of neurotransmitters and neuromodulators including adenosine 5′-triphosphate (ATP). Carotid body cells and nerve fibre terminals express ATP receptors, i.e., purinergic receptors. Here we used double immunofluorescence associated with laser confocal microscopy to detect the ATP receptor P2X7 and pannexin 1 (an ATP permeable channel) in the human carotid body, as well as the petrosal and cervical sympathetic ganglia. Immunofluorescence for P2X7r and pannexin 1 forms a broad cellular network within the glomeruli of the carotid body, whose pattern corresponds to that of type II cells. Moreover, both P2X7r and pannexin 1 were also detected in nerve profiles. In the petrosal ganglion, the distribution of P2X7r was restricted to satellite glial cells, whereas in the cervical sympathetic ganglion, P2X7r was found in neurons and glial satellite cells. The role of this purinergic receptor in the carotid body, if any, remains to be elucidated, but it probably provides new evidence for gliotransmission. Full article

We examined whether an increase in synaptic activity resulted in an increase in quantal size at the neuromuscular junction (NMJ) of third-instar Drosophila larvae. Spontaneous miniature excitatory postsynaptic currents (mEPSCs) or miniature excitatory postsynaptic potentials (mEPSPs) were recorded before and after nerve stimulation. We found that prolonged (60 s) or brief (1.25 s) nerve stimulation produced an increase in quantal size; this appears to be a general property of these synapses since it was seen at all four muscle fibers (MFs) used in this study. The effect was examined along Is and Ib terminals by expressing GCaMP in the MF membrane and examining postsynaptic Ca²⁺ signals produced by spontaneous transmitter release. The activity-dependent increase in quantal size occurred at both Is and Ib terminals, and the increase in frequency and amplitude of quantal events at individual synaptic boutons was correlated. Both the increase in quantal size and frequency were found to be dependent upon an increase in postsynaptic Ca²⁺, based on studies in which MFs were preinjected with the Ca²⁺ chelator BAPTA (1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). To examine the effect of postsynaptic activity on glutamate sensitivity, we iontophoresed glutamate pulses at the NMJ and recorded the glutamate-evoked excitatory postsynaptic potentials (gEPSPs). Trains of glutamate pulses produced an increase in gEPSP amplitude; this potentiation was not seen when Ca²⁺ was eliminated from the bath or after inhibiting calmodulin or CaMKII. The activity-dependent increase in quantal size may result from an increase in postsynaptic sensitivity due to activation of CaMKII. Full article

In most vertebrates, males and females display distinct reproductive behaviors. Some fish can change their sexual phenotype at various life stages, which involves alterations in their gonadal sex and changes in their reproductive behavior to align with the new gonadal identity. Although the sex reversal phenomenon in reproductive behavior is well documented, the underlying mechanisms in the brains of these fish remain largely unknown. In the present study, we investigated the roles of the thyroid hormone (triiodothyronine (T3)) in the Mozambique tilapia as a potential regulator of male-specific nest-building behavior and gonadotropin-releasing hormone-3 (GnRH3) neurons, the regulatory neurons of male reproductive behavior, in the terminal nerve (TN) ganglion. T3 injection successfully induced nest-building behavior in mature female fish. T3 injection significantly elevated serum T3 concentrations in treated animals compared with those in controls. Through organotypic culture of brain slices that included the TN region, we demonstrated that T3 could stimulate an increase in the number of GnRH3 neurons, and the effect was inhibited by a thyroid hormone receptor (TR) inhibitor. Additionally, TRβ co-expression was observed in GnRH3 neurons. These findings highlight the crucial roles of T3 and GnRH3 in sex reversal processes within the fish brain. Full article

Background: Brachial plexopathies comprise a diverse array of illnesses with multifactorial etiologies, including trauma, inflammation, neoplasia, and iatrogenic damage, frequently manifesting with nonspecific clinical symptoms. Precise and prompt imaging evaluation is essential for diagnosis, treatment planning, and monitoring. Objective: To equip radiologists with interpretative tools for a systematic assessment of the brachial plexus utilizing advanced imaging modalities, specifically ultrasound (US) and magnetic resonance imaging (MRI), while emphasizing techniques, indications, limitations, and critical radiologic signs for differential diagnosis. Imaging Techniques: This narrative review concentrates on US and MRI. High-frequency linear probes with multiplanar dynamic scans provide US visualization of trunks, cords, and terminal branches in superficial areas. Specialized MRI procedures (T1, T2, STIR, DWI, contrast-enhanced) provide comprehensive evaluation of spinal roots and deep tissues, differentiating preganglionic from postganglionic lesions. A combined US–MRI methodology can enhance diagnostic efficacy. Findings: Ultrasound is excellent for superficial and dynamic assessment, especially in post-traumatic and iatrogenic lesions, while MRI is the gold standard for deep structures and complex disorders. The integration of two modalities enhances lesion identification and treatment direction. Emerging methodologies further enhance diagnostic and prognostic capabilities. Conclusions: The synergistic application of US and MRI, emphasizing nerve injury patterns and muscle denervation indicators, facilitates precise and prompt diagnosis of brachial plexopathies. Standardizing imaging standards and incorporating modern techniques are essential for interdisciplinary, customized patient care. Full article