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Emerging molecular therapeutic targets for spinal cord injury.

Introduction: Spinal cord injury (SCI) is a complicated and devastating neurological disorder. Patients with SCI usually have dramatically r … cent advances in biological and molecular strategies to enhance neuroprotection, axon regeneration, remyelination, neuroplasticity and functional recovery in preclinical studies of SCI. Expert opinion: Researchers have made tremendous progress in identifying individual and combined molecular therapies in animal studies. It is very important to identify addition …

Treatment of internuclear ophthalmoparesis in multiple sclerosis with fampridine: A randomized double-blind, placebo-controlled cross-over trial.

AIM: To examine whether the velocity of saccadic eye movements in internuclear ophthalmoparesis (INO) improves with fampridine treatment in … nts due to INO in MS. Treatment response to fampridine may gauge patient selection for inclusion to remyelination strategies in MS using saccadic eye movements as primary outcome measure.

Local injection of Lenti-Olig2 at lesion site promotes functional recovery of spinal cord injury in rats.

AIMS: Olig2 is one of the most critical factors during CNS development, which belongs to b-HLH transcription factor family. Previous reports have shown that Olig2 regulates the remyelination processes in CNS demyelination diseases models. However, the role of Olig2 in contusion spinal cord injury (SCI) and the possible therapeutic effects remain obscure. This study aims to investigate the effects of overexpression Olig2 by lentivirus on adult spinal cord injury rats. METHODS: Lenti-Olig2 expression and control Lenti-eGFP vectors were prepared, and virus in a total of 5 μL (108 TU/mL) was loca…

Thermosensitive heparin-poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury.

Traumatic spinal cord injury (SCI) results in paraplegia or quadriplegia, and currently, therapeutic interventions for axonal regeneration after SCI are not clinically available. Animal studies have revealed that glial cell-derived neurotrophic factor (GDNF) plays multiple beneficial roles in neuroprotection, glial scarring remodeling, axon regeneration and remyelination in SCI. However, the poor physicochemical stability of GDNF, as well as its limited ability to cross the blood-spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice.…

Quercetin promotes motor and sensory function recovery following sciatic nerve-crush injury in C57BL/6J mice.

Injuries and diseases that occur in the nervous system are common and have few effective treatments. Previous studies have shown that querce … to neuronal growth activation in peripheral axon regeneration. In addition, quercetin enhanced axon remyelination, motor nerve conduction velocity and plantar muscle function, indicating that the degree of distal portion hypotrophy during the peripheral axon regeneration process was reduced. These results suggest that quercetin accelerates functional recovery b …

White matter loss in a mouse model of periventricular leukomalacia is rescued by trophic factors.

Periventricular leukomalacia (PVL) is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME) leads to abnormal oligodendrocytes (OLs), myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1) promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA). Com…

Selective vulnerability of peripheral nerves in avian riboflavin deficiency demyelinating polyneuropathy.

Riboflavin (vitamin B2) deficiency in young chickens produces a demyelinating peripheral neuropathy. In this study, day-old broiler meat chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and killed on posthatch days 6, 11, 16, 21, and 31, while control chickens were given a conventional diet containing 5.0 mg/kg riboflavin. Pathologic changes were found in sciatic, cervical, and lumbar spinal nerves of riboflavin-deficient chickens from day 11 onwards, characterized by endoneurial oedema, hypertrophic Schwann cells, tomacula (redundant myelin swellings), demyelination/remyelination, li…

Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury.

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after … to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist p …

Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study.

Disruptions in oxidative metabolism may occur in multiple sclerosis and other demyelinating neurological diseases. The impact of demyelinati … r (-62.1%, p ≤ 0.001). These changes resolved after the cessation of cuprizone exposure and partial remyelination. A decrease in hemoglobin concentration (-34.4%, p ≤ 0.001), but no change in cerebral blood flow were also observed during demyelination. The oxidized state of the mitochondrial enzyme, Cytochrome C Oxidase (CCO) increased (46.3%, p ≤ 0.001) while …

Imaging resident and recruited macrophage contribution to Wallerian degeneration.

Wallerian degeneration (WD) is a process of autonomous distal degeneration of axons upon injury. Macrophages (MPs) of the peripheral nervous system (PNS) are the main cellular agent controlling this process. Some evidence suggests that resident PNS-MPs along with MPs of hematogenous origin may be involved, but whether these two subsets exert distinct functions is unknown. Combining MP-designed fluorescent reporter mice and coherent anti-Stokes Raman scattering (CARS) imaging of the sciatic nerve, we deciphered the spatiotemporal choreography of resident and recently recruited MPs after injury

Walnut-Derived Extracellular Vesicles Orchestrate a Pre-Regenerative Niche via c-Myc Mediated Metabolic Reprogramming.

Peripheral nerve injury (PNI) remains a major regenerative challenge, in part because the post-injury microenvironment can disrupt Schwann c … ere associated with preserved mitochondrial ultrastructure in the acute phase, followed by enhanced remyelination, improved motor and sensory outcomes, and attenuated muscle atrophy. Collectively, our findings suggest a mechanistic basis for the reported neuroprotective value of walnuts and identify WEVs as a niche-modulating nanotherapeutic candidate that may …

NG2 Glia and Cellular Crosstalk in Health and Disease: Focus on Spinal Cord Injury.

NG2 glia, also known as oligodendrocyte progenitor cells, represent a unique population of glial cells characterized by dynamic morphology and the ability to extend branched processes that actively contact neurons and other cellular elements. These structural and functional interactions enable NG2 glia to contribute to the regulation of axonal excitability, electrical activity, and axonal architecture. Unlike most other glial cells, NG2 glia receive direct synaptic input from neurons and can generate action potentials, defining their distinctive physiological status. A particularly important f

Modulation of the immunological and neuroinflammatory microenvironment in older people with multiple sclerosis.

Life expectancy and the age at onset of multiple sclerosis (MS) are increasing, and a growing proportion of people with MS (pwMS) are now older than 55-60 years. Aging modifies MS pathobiology, with the dominant disease mechanisms moving from focal, relapse-driven inflammation to chronic, compartmentalized neuroinflammation and neurodegeneration. In this narrative review, we summarize current knowledge on the relationship between brain aging and MS, integrating clinical, radiological, pathological and therapeutic evidence. We first discuss mechanisms of immunosenescence and "inflammaging", inc

An Autophagy-Sensitive Nanoplatform via Chirality-Selective Modulation for Functional Peripheral Nerve Repair and Target Organ Homeostasis.

Peripheral nerve injury (PNI) and diabetic peripheral neuropathy (DPN) are prevalent and destructive problems in clinical practice; however, there is currently no precise strategy for them despite a wide range of attempts due to their ambiguous neuromodulation effects. Accumulating evidence indicates the opposite functions of chiral enantiomers in various diseases, suggesting that chirality-selective modulation should be investigated. Herein, Fe3O4 nanoparticle enantiomers were synthesized to clarify the concept of chirality-selective neuromodulation, followed by mechanistic investigation. Ner

Adenylyl Cyclases as Therapeutic Targets in Neuroregeneration.

Adenylyl cyclases (ACs) are key regulators of cyclic adenosine monophosphate (cAMP) signaling-a pathway critical for neuroregeneration, syna … ) receptor signaling has shown therapeutic promise in preclinical models by enhancing neurogenesis, remyelination, and synaptic repair. Conversely, targeted inhibition of specific AC isoforms, particularly AC1, has demonstrated efficacy in reducing maladaptive plasticity and neuropathic pain. This review highlights the diverse roles of ACs in neuronal function …

The Neuroregenerative Effects of IncobotulinumtoxinA (Inco/A) in a Nerve Lesion Model of the Rat.

The use of Botulinum Neurotoxin A (BoNT/A) to treat peripheral neuropathic pain from nerve injury has garnered interest for its long-lasting … -treated group, suggesting accelerated functional nerve recovery. Tissue analysis revealed enhanced remyelination in Inco/A-treated animals and 60% reduction in CGRP and double S100β signal expression compared to controls. Strikingly, 30% reduced immune cell influx into the injury site was observed following Inco/A treatment, suggesting that its anti-inflammato …

Нейропзащитное воздействие анальгецина путем изменения метаболизма холестерина в модели мышей EAE, модели множественного склероза.

Множественный склероз (MS) — хроническое аутоиммунное неврологическое заболевание, характеризующееся воспалительным демиэлированием. Терапевтические альтернативы НР по-прежнему ограничены. Меры по улучшению холестерина, гомеостазиса, возможно, являются эффективным подходом к содействию воссоединению пациентов с НР. Анальгецин (AGC), выдержка из кролика с вакцинацией, используется в клиническом лечении низкой боли в спине. Ранее мы обнаружили, что СМЖЛ имеет нейрозащитный эффект. В настоящем исследовании мы стремились выявить воздействие и механизм СМЖЛ на гомеостаз холестерина в модели MS. В э

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune neurological disease characterized by inflammatory demyelination damage. Therapeutic alternatives for MS are still limited. Interventions to improve cholesterol homeostasis may be a viable approach to promoting the remyelination of MS patients. Analgecine (AGC), the extracts of Vaccinia-inoculated rabbit skin, …

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis.

BACKGROUND: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up. METHODS: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quan…

Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair.

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application … face as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, ach …