Search Results (451)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article

The internal branch of the superior laryngeal nerve (IbSLN) plays a critical role in the sensory innervation of the supraglottic larynx. It is essential for protective reflexes such as coughing and swallowing. This nerve is frequently at risk during surgeries involving the cervical region, including thyroidectomy, carotid endarterectomy, and anterior cervical spine procedures. Injury to the IbSLN may lead to postoperative complications. A comprehensive review of the morphological and topographic characteristics of the IbSLN is presented, focusing on its anatomical course, relationships with key vascular structures, branching patterns, and clinically significant variations. Full article

Background: Numerous experimental studies aim to improve outcomes of peripheral nerve repair following trauma. This study evaluates the efficacy of the human epineural patch (hEP) compared to the human amniotic membrane (hAM) in promoting nerve regeneration following sciatic nerve crush injury. Methods: Thirty-six athymic nude rats were divided into three groups (n = 12 per group) following nerve crush: (1) an unprotected injury site; (2) crush injury wrapped with hEP; and (3) crush injury wrapped with hAM. Animals were assessed over 6 or 12 weeks post-injury. Evaluations included motor recovery (Toe-Spread test), sensory recovery (Pinprick test), muscle denervation atrophy (the gastrocnemius muscle index (GMI)), histomorphometry (myelin thickness, axonal density, fiber diameter, and percentage of myelinated fibers), and immunofluorescence (GFAP, Laminin B, NGF, S-100, VEGF, vWF, HLA-DR, and HLA-I) assessments. Results: The hEP group showed superior motor recovery, axonal density and higher GMI values compared to the hAM and control groups. The increased expression of neurogenic and angiogenic markers highlighted its neuroregenerative potential. Negligible HLA-DR and HLA-I expression confirmed the lack of hEP and hAM immunogenicity. Conclusions: The application of hEP following sciatic nerve crush injury facilitated nerve regeneration, improved functional outcomes, and offered a viable alternative to hAM. Structural stability and the regenerative capacity position hEP as a new, promising off-the-shelf product for nerve regeneration. Full article

The accurate identification and protection of the lingual nerve during oral surgery are critical to avoid complications such as a loss of taste or sensation and chronic pain. While numerous studies have described the nerve’s anatomy and injury outcomes, no consensus exists on the optimal method to trace its full course. This narrative review systematically examined the literature from 2010 to 2024, using databases like PubMed, MEDLINE, Embase, and Google Scholar. Keywords included “Lingual nerve,” “Course,” “Anatomy,” and “Clinical implications,” combined with Boolean operators. Studies were selected based on defined criteria, and findings were synthesized to highlight key challenges in diagnosing the nerve’s path. This review identifies difficulties at multiple anatomical sites: the foramen ovale, infratemporal fossa, pterygomandibular space, third molar and retromolar regions, premolar/molar areas, floor of the mouth, and anterior gingiva and tongue. Lingual nerve injury, especially during lower third molar surgeries, remains a major concern, often exacerbated by factors like patient age, unerupted teeth, and lingual surgical approaches. Effective prevention hinges on precise anatomical knowledge and meticulous surgical technique. Microsurgical repair remains the primary treatment but often yields unpredictable outcomes. Emerging regenerative therapies show early promise but require further clinical validation. Imaging tools such as magnetic resonance imaging (MRI) and ultrasound may enhance diagnostic accuracy and surgical planning; however, each has limitations in everyday practice. Ultimately, early identification, careful surgical handling, and appropriate imaging support are vital for improving patient outcomes and minimizing the risks of lingual nerve injury. Full article

Docetaxel is extensively used for treating different types of cancer; however, its clinical efficacy is primarily limited by myelotoxicity and peripheral neuropathy, adverse effects that often lead to treatment discontinuation. This study aimed to establish a preclinical model in Wistar rats for the simultaneous induction of myelotoxicity and peripheral neuropathy associated with docetaxel administration, enabling the evaluation of potential chemopreventive agents. Four distinct docetaxel administration schemes were assessed by performing behavioral nociceptive tests and complete blood cell counts. After establishing the damage model (5 mg/kg/week docetaxel for six weeks), we co-administered 100 mg/kg/week oral dimethyl fumarate to assess its protective effect. Dimethyl fumarate attenuated docetaxel-induced hyperalgesia, likely through preserving normal nerve fiber density in sciatic nerves, but neutropenia was not significantly mitigated. An alternative regimen with additional pre-administered doses of dimethyl fumarate showed a trend toward neutropenia attenuation and suggested an interesting inhibition of docetaxel-induced rat vibrissae loss. Chou-Talalay isobolographic analyses on prostate cancer cell lines revealed that dimethyl fumarate does not impair the therapeutic effect of docetaxel at most combination ratios evaluated; rather, synergistic effects were observed. This experimental model proved useful and will facilitate further research into the protective role of dimethyl fumarate and other potential chemoprotective agents. Full article

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (Aβ) accumulation, tau pathology, and neuroinflammation in the Al/D-galactose-induced rat model (Al/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced Aβ aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism. Full article

Background: Previous studies have indicated that transcutaneous electrical nerve stimulation (TENS) is highly effective in improving the treatment of neuropathy and achieving maximum recovery in the shortest time. However, its effectiveness in the early stages of the disease has not been studied, and no comparative analysis has been conducted between different modalities of TENS. Materials and Methods: This study included 82 patients with acute and subacute fibular tunnel (FT) syndrome lasting no more than 15 days. Patients were randomized into the following four groups depending on the modality of TENS used: sham TENS (20 patients), HF TENS (20 patients), LF TENS (21 patients), and a combined HF/LF TENS group (21 patients). Before treatment, immediately after treatment, and 3 months after the end of treatment patients were examined to determine the severity of hypoesthesia, motor deficit, and gait disturbance. Results: The reduction in hypoesthesia averaged after HF TENS, LF TENS, and sham TENS was 50.7% (p ≤ 0.01), 37.8 (p ≤ 0.01), and 11.4% (p > 0.05), respectively. The regression of motor deficit and gate disorders reached 61% after LF TENS (p ≤ 0.01), 6% after HF TENS (p > 0.05), and 6% (p > 0.05) after sham TENS. The combination of HF and LF TENS resulted in a 54.8% (p ≤ 0.01) reduction in hypoesthesia and 61.3% (p ≤ 0.01) regression of motor deficit, with a superior 30% (p ≤ 0.05) improvement in quality of life compared to separate use of HF and LF TENS. Conclusions: Early use of TENS in the treatment of FT syndrome turned out to be highly effective compared to sham TENS in reducing hypoesthesia, motor deficit, and gait disturbance. The analgesic effect and sensory recovery were higher after HF TENS. Motor and gait disturbances were reduced only after LF TENS, with evidence of prolonged regenerative and protective effect for at least 3 months after the end of treatment. The combination of HF TENS and LF TENS increases the therapeutic range of TENS with the achievement of the maximum positive effect of HF TENS and LF TENS after treatment and during the long-term period, which leads to a more pronounced improvement in the quality of life of patients with this pathology. Full article

The skin is the body’s largest organ. It serves various functions, including protection and metabolism. Due to its structure and location, it is more vulnerable to external physical and chemical damage than internal organs. Additionally, certain endogenous diseases can cause pathological changes to appear on the skin and nerves. When skin tissue breaks down or sustains severe trauma, the cells, blood vessels, and nerves across all layers can suffer varying degrees of damage. This often results in pain, itching, sensory disturbances, and other discomforts, causing significant distress to patients. Stem-cell-derived exosome therapy has emerged as a promising treatment for skin injuries due to its safety, non-toxicity, and precision medicine benefits. Research has shown that stem-cell-derived exosomes regulate nerve cells by mediating MicroRNA (miRNA) transport and expression between cells, promoting axon growth. This exosome-driven miRNA exchange serves as a vital mode of intercellular communication, playing a crucial role in nervous system repair. Nerves play a critical role in skin wound healing and tissue regeneration, with sensory and autonomic nerves influencing key skin functions such as inflammation, immune defense, apoptosis, proliferation, and wound repair. Exosomes may aid in treating cutaneous nerve injuries by directly or indirectly promoting axon regeneration, nerve cell proliferation, and the release of protective neurofactors. Full article

Ischemic stroke (IS) is a high-mortality, multi-complication cardiovascular disease. Reducing brain injury and promoting neuronal repair after IS onset remain important challenges for current treatments. Our team previously found that PAS840, an extract from Periplaneta americana (L.), protects nerve function; this study further uses LC-MS/MS and peptidomics to analyze PAS840’s components and network pharmacology to predict its ischemic stroke (IS) therapeutic targets. We then employed Transwell, a biochemical kit, real-time quantitative polymerase chain reaction (RT-qPCR), and transcriptomics to investigate PAS840’s effects on migration ability, oxidative stress levels, and cellular pathways in mouse microglial cells (BV-2) following oxygen–glucose deprivation/reoxygenation (OGD/R) injury. Finally, using Evans blue staining, immunohistochemical analysis, and RT-qPCR, we investigated PAS840’s effects on the blood–brain barrier, inflammation pathways, and neural function in a transient middle cerebral artery occlusion (tMCAO) rat model. PAS840 components target multiple IS pathways, effectively inhibit NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway activation in BV-2 cells following OGD/R, reduce cellular oxidative stress, inflammation, and pyroptosis, and improve cell viability and migration ability. PAS840 decreases NF-κB/NLRP3/Caspase-1/IL-1β inflammasome pathway expression in tMCAO rat brains, reduces inflammation, activates BDNF/VGF/NGR1/Erbb4 neurotrophic factor and vascular endothelial growth factor pathways, enhances neuronal cell viability, and effectively protects and repairs the blood–brain barrier. Full article

A major challenge in developing new functional foods is effectively protecting and releasing bioactive compounds in specific body areas. The Multiform Administration Timed Release Ingredients System (M.A.T.R.I.S.) is an innovative method that coats active ingredient particles with a permeable membrane, allowing for diffusion without the presence of inactive materials. This study aimed to test how M. A. T. R. I. S. modulated the absorption and effects of two molecules: α-lipoic acid and acetyl-L-carnitine. This study examined the structures of these molecules with or without M.A.T.R.I.S. and investigated their intestinal absorption. Peripheral nervous system analyses were also conducted to confirm the ability of substances to maintain their functions in the presence of M.A.T.R.I.S. Results showed that M.A.T.R.I.S. modulated the absorption of both molecules compared to granular raw material forms (p < 0.05). Additionally, the M.A.T.R.I.S. molecules better supported peripheral nerve well-being than their granular raw material forms (p < 0.05). In conclusion, this study demonstrates that M.A.T.R.I.S. technology can be used to create innovative, safe treatments by enhancing absorption mechanisms to improve the effectiveness of substances in reaching their specific targets. Full article

Background: Treating varicosities originating from a popliteal fossa perforating vein (PFPV) is challenging due to their proximity to nerves and complex morphology. Data on endovenous laser ablation (EVLA) for PFPV varicosis are limited. Methods: This retrospective, single-center study reviewed all primary varicose vein surgeries from May 2021 to December 2024. Only primary PFPV varicosis cases with CEAP stage C2s or higher were included. Patients with recurrent disease or primary truncal insufficiency due to reflux from the saphenopopliteal junction were excluded. EVLA was performed using 1470 nm radial laser catheters, targeting the reflux source and downstream varicose segments. Tumescent solution was applied to protect the surrounding structures. The primary outcome was early technical success via duplex ultrasound; the secondary outcome was the complication rate. Results: Of the 2375 limbs treated, 44 (1.9%) involved PFPV. The cohort included 16 men (36%) and 28 women (64%), with a mean age of 54. The median follow-up was 14 days. Technical success was achieved in 41 cases (93.2%). Foam sclerotherapy with polidocanol was performed in eight patients (18.2%), exclusively for superficial residual varicosities and never simultaneously with EVLA. Three treatment failures required re-operation, two of which were successfully re-treated. Minor postoperative complications occurred in two patients (4.5%). No nerve injuries or thrombotic events were observed. Conclusions: EVLA shows promising very early technical efficacy, with low morbidity, for treating PFPV varicosis. Based on our findings, prospective studies investigating the mid- and long-term outcomes of this technique are warranted to further validate its clinical utility. Full article

Background: Glaucoma is a leading cause of irreversible visual loss worldwide, characterized by progressive retinal ganglion cell (RGC) degeneration and optic nerve damage. Current therapies mainly focus on lowering intraocular pressure (IOP), yet fail to address pressure-independent neurodegenerative mechanisms. Melatonin, an endogenously produced indoleamine, has gained attention for its potential in modulating both IOP and neurodegeneration through diverse cellular pathways. This review evaluates the therapeutic relevance of melatonin in glaucoma by examining its mechanistic actions and emerging delivery approaches. Methods: A comprehensive literature search was conducted via PubMed and Medline to identify studies published between 2000 and 2025 on melatonin’s roles in glaucoma. Included articles discussed its effects on IOP regulation, RGC survival, oxidative stress, mitochondrial integrity, and inflammation. Results: Evidence supports melatonin’s involvement in IOP reduction via MT receptor activation and its synergism with adrenergic and enzymatic regulators. Moreover, it protects RGCs by mitigating oxidative stress, preventing mitochondrial dysfunction, and inhibiting apoptotic and inflammatory cascades. Recent advances in ocular drug delivery systems enhance its bioavailability and therapeutic potential. Conclusions: Melatonin represents a multi-target candidate for glaucoma treatment. Further clinical studies are necessary to establish optimal dosing strategies, delivery methods, and long-term safety in patients. Full article

Background: The brachial plexus is a network of nerves responsible for the motor and sensory innervation of the upper limb. Variations in the formation and course of the brachial plexus are well documented, though combinations of multiple unilateral abnormalities are rare. The complex pathology of this structure nerve may result in clinical consequences. We present a unique set of brachial plexus abnormalities involving the C4–C6 nerve roots, superior and middle trunks, additional communicating branches, and delayed median nerve union. Case Presentation: During the routine dissection of a 70-year-old female cadaver, several unique variations in the brachial plexus anatomy were identified. The C4 root contributed to C5 before the superior trunk formed, resulting in a superior trunk composed of C4–C6. The C5 root was located anterior to the anterior scalene muscle, whereas C6 maintained its usual posterior position. Additionally, an anterior communicating branch from the middle trunk to the posterior cord was observed. A communicating branch between the lateral and medial cords split into two terminal branches: one merged with the ulnar nerve, and the other joined the medial contribution of the median nerve. The median nerve contributions from the lateral and medial cords merged approximately two inches above the elbow. Conclusions: This rare combination of brachial plexus anomalies has not been previously described in the literature and is of significant clinical relevance. The additional anterior communicating branch from the middle trunk may suggest potential flexor muscle innervation by the posterior cord, which typically innervates extensor muscles. Additionally, the delayed convergence of the median nerve may provide a protective mechanism in cases of midshaft humeral fracture. Awareness of these peripheral nerve abnormalities is important for diagnostic imaging, surgery, or peripheral nerve blocks. Knowledge of such variations is critical for clinicians managing upper limb pathologies. Full article

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase activity to result in a correctly folded protein(s). In this study, we aimed to investigate the effects of the heterozygous DNAJB2 c.823+6C>T mutation on the stress response of DNAJB2 in fibroblasts obtained from the neuropathy patient. Methods: The fibroblasts were subjected to one hour of heat shock at 42 °C, and the time course of expression levels of DNAJB2 was established. Additionally, we evaluated the therapeutic efficacy of Cystamine, which has been shown to modulate DNAJB2 levels in cellular and animal models of Huntington’s disease. Results: Our results revealed reduced baseline levels of DNAJB2 between the mutant and control fibroblasts. Importantly the mutant cells exhibited a diminished response to heat shock. Thus, the mutation affects the upregulation of DNAJB2 under stress, possibly contributing to the pathogenesis of sensory–motor polyneuropathy. A 48-h pretreatment with 150 μM of Cystamine increased the levels of DNAJB2 in both the control and patient’s fibroblasts. Conclusions: To the best of our knowledge, this is the first study to explore this mutant form of DNAJB2 in neuropathy. The study demonstrated that the heterozygous DNAJB2 c.823+6C>T mutation leads to impaired DNAJB2 response to heat shock in the fibroblasts. Cystamine showed promise in restoring DNAJB2 expression, highlighting the need for further research into targeted therapeutic strategies for DNAJB2-related disorders. Full article