Neural Regeneration Research

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Neural Regeneration Research Neural Regeneration Research (NRR) is a peer-reviewed OA journal published monthly, indexed by SCI-E, PubMed, SCOPUS and etc.. 2022 JCR Impact Factor is 6.1.
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NRR aims to duly report basic and clinical research in the field of neuroregeneration.

       Role of exercise in the brain: focus on oligodendrocytes and remyelination
14/06/2024


Role of exercise in the brain: focus on oligodendrocytes and remyelination

An abstract is unavailable.

     Molecular chaperones in stroke-induced immunosuppressionhttps://journals.lww.com/nrronline/fulltext/2023/12000/mole...
13/06/2024


Molecular chaperones in stroke-induced immunosuppression
https://journals.lww.com/nrronline/fulltext/2023/12000/molecular_chaperones_in_stroke_induced.15.aspx

Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome. Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections, such as urinary tract infections and stroke-associated pneumonia, worsening prognosis. Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains, refolding misfolded proteins, and targeting misfolded proteins for degradation. Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones, cochaperones, and their associated pathways. This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.

           Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cellshttps://jou...
13/06/2024


Therapies for Tau-associated neurodegenerative disorders: targeting molecules, synapses, and cells
https://journals.lww.com/nrronline/fulltext/2023/12000/therapies_for_tau_associated_neurodegenerative.14.aspx
University of Cambridge

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating (1) the broad class of chemicals termed “small molecules”; (2) adaptive immunity through both passive and active antibody treatments; (3) innate immunity with an emphasis on microglial modulation; (4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer’s disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer’s disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.

   Potential role of Lycium barbarum polysaccharides in glaucoma management: evidence from preclinical in vivo studiesht...
13/06/2024


Potential role of Lycium barbarum polysaccharides in glaucoma management: evidence from preclinical in vivo studies
https://journals.lww.com/nrronline/fulltext/2023/12000/potential_role_of_lycium_barbarum_polysaccharides.13.aspx

In recent years, the pharmacological benefits of herbal extracts have been revisited for their potential neuroprotective effects in glaucoma. The polysaccharides extracted from the fruits of Lycium barbarum L., or Lycium barbarum polysaccharides, exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhancing neuronal responses, and promoting cytoprotection. The therapeutic efficacy of Lycium barbarum polysaccharides in preserving retinal ganglion cells and their functions was demonstrated in a range of experimental models of optic neuropathies. These include the acute and chronic ocular hypertension models, the partial optic nerve transection model, and the ischemic-reperfusion injuries model. Based on these findings, Lycium barbarum polysaccharides appear to be a good candidate to be developed as a neuroprotective agent for treating multifactorial diseases. This review aims to present a comprehensive review on the latest preclinical evidence on the pre- and post-treatment benefits of Lycium barbarum polysaccharides in retinal ganglion cell neuroprotection. The possible mechanisms of Lycium barbarum polysaccharides mediating retinal ganglion cell neuroprotection will also be described. Moreover, the potential research gaps in the effective translation of Lycium barbarum polysaccharides treatment into clinical glaucoma management will be discussed.

     Retinoprotective compounds, current efficacy, and future prospectivehttps://journals.lww.com/nrronline/fulltext/202...
13/06/2024


Retinoprotective compounds, current efficacy, and future prospective
https://journals.lww.com/nrronline/fulltext/2023/12000/retinoprotective_compounds,_current_efficacy,_and.11.aspx

Retinal dysfunction is the most common cause of vision loss in several retinal disorders. Among different types of retinopathies, we can account some that share causes, symptoms, and treatment including diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa. Molecular changes, environmental factors, and genetic predisposition might be some of the main causes that drive retinal tissue to chronic inflammation and neurodegeneration in these retinopathies. The treatments available on the market contain compounds that efficiently ameliorate some of the important clinical features of these pathologies like stabilization of the intraocular pressure, reduction of eye inflammation, control of eye oxidative stress which are considered the major molecular mechanisms related to retinal dysfunction. Indeed, the most commonly used drugs are anti-inflammatories, such as corticosteroids, antioxidant, hypotonic molecules and natural neuroprotective compounds. Unfortunately, these drugs, which are fundamental to treating disease symptoms, are not capable to cure the pathologies and so they are not life-changing for patients. This review provided an overview of current treatments on the market, but more interestingly, wants to be a quick window on the new treatments that are now in clinical trials. Additionally, it has been here highlighted that the recent technical enhancement of the investigation methods to identify the various retinopathies causes might be used as a sort of “precise medicine” approach to tailor the identification of molecular pathways involved and potentially study a dedicated treatment for each patient. This approach includes the use of cutting-edge technologies like gene therapy and metabolomics.

   Animal models of vascularized nerve grafts: a systematic reviewhttps://journals.lww.com/nrronline/fulltext/2023/12000...
11/06/2024


Animal models of vascularized nerve grafts: a systematic review
https://journals.lww.com/nrronline/fulltext/2023/12000/animal_models_of_vascularized_nerve_grafts__a.10.aspx
Università degli Studi di Palermo

The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts.

         Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson’s ...
11/06/2024


Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson’s disease
https://journals.lww.com/nrronline/fulltext/2023/12000/gut_microbiome_brain_axis__the_crosstalk_between.9.aspx
Universidade Federal do Ceará - UFC

This critical review of the literature shows that there is a close link between the microbiome, the gut, and the brain in Parkinson’s disease. The vagus nerve, the main component of the parasympathetic nervous system, is involved in the regulation of immune response, digestion, heart rate, and control of mood. It can detect microbiota metabolites through its afferents, transferring this gut information to the central nervous system. Preclinical and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression, as well as treatment responses. These findings suggest that the gut microbiome may be a valuable target for new therapeutic strategies for Parkinson’s disease. More studies are needed to better understand the underlying biology and how this axis can be modulated for the patient’s benefit.

ntrol of mood. It can detect microbiota metabolites through its afferents, transferring this gut information to the central nervous system. Preclinical and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression, as w...

       Saliva: a challenging human fluid to diagnose brain disorders with a focus on Alzheimer’s diseasehttps://journals...
07/06/2024


Saliva: a challenging human fluid to diagnose brain disorders with a focus on Alzheimer’s disease
https://journals.lww.com/nrronline/fulltext/2023/12000/saliva__a_challenging_human_fluid_to_diagnose.8.aspx
Medizinische Universität Innsbruck

Biomarkers are molecules of biological processes that help in both the diagnosis of human diseases and in follow-up assessments of therapeutic responses. Biomarkers can be measured in many human fluids, such as blood, cerebrospinal fluid, urine, and saliva. The -omics methods (genomics, RNomics, proteomics, and metabolomics) are useful at measuring thousands of markers in a small volume. Saliva is a human fluid that is easily accessible, without any ethical concerns. Yet, saliva remains unexplored in regard to many human disease biomarkers. In this review, we will give an overview on saliva and how it can be influenced by exogenous factors. As we focus on the potential use of saliva as a diagnostic tool in brain disorders (especially Alzheimer’s disease), we will cover how saliva is linked to the brain. We will discuss that saliva is a heterogeneous human fluid, yet useful for the discovery of biomarkers in human disorders. However, a procedure and consensus that is controlled, validated, and standardized for the collection and processing of saliva is required, followed by a highly sensitive diagnostic approach.

     CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trialhttps://journals.lww.com/n...
07/06/2024


CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial
https://journals.lww.com/nrronline/fulltext/2023/12000/cdp_choline_to_promote_remyelination_in_multiple.7.aspx

Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death, resulting in functional disability. Remyelination is the natural repair process of demyelination, but it is often incomplete or fails in multiple sclerosis. Available therapies reduce the inflammatory state and prevent clinical relapses. However, therapeutic approaches to increase myelin repair in humans are not yet available. The substance cytidine-5′-diphosphocholine, CDP-choline, is ubiquitously present in eukaryotic cells and plays a crucial role in the synthesis of cellular phospholipids. Regenerative properties have been shown in various animal models of diseases of the central nervous system. We have already shown that the compound CDP-choline improves myelin regeneration in two animal models of multiple sclerosis. However, the results from the animal models have not yet been studied in patients with multiple sclerosis. In this review, we summarise the beneficial effects of CDP-choline on biolipid metabolism and turnover with regard to inflammatory and regenerative processes. We also explain changes in phospholipid and sphingolipid homeostasis in multiple sclerosis and suggest a possible therapeutic link to CDP-choline.

sclerosis. Available therapies reduce the inflammatory state and prevent clinical relapses. However, therapeutic approaches to increase myelin repair in humans are not yet available. The substance cytidine-5′-diphosphocholine, CDP-choline, is ubiquitously present in eukaryotic cells and plays a cr...

   Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer’s disease?https://jo...
07/06/2024


Thinking outside the black box: are the brain endothelial cells the new main target in Alzheimer’s disease?
https://journals.lww.com/nrronline/fulltext/2023/12000/thinking_outside_the_black_box__are_the_brain.6.aspx
Hospital Juárez de México

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport. Although brain endothelial cell function is crucial for brain homeostasis, their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia, astroglia, neurons, or even molecules such as amyloid beta, Tau, or alpha-synuclein. Alzheimer’s disease is the most common neurodegenerative disease, and brain endothelial cell dysfunction has been reported by several groups. However, its impairment has barely been considered as a potential therapeutic target. Here we review the most recent advances in the relationship between Alzheimer’s disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease, highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment. Finally, we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer’s disease.

       The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer’s disease: a narrative ...
07/06/2024


The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer’s disease: a narrative review
https://journals.lww.com/nrronline/fulltext/2023/12000/the_role_of_natural_flavonoids_on.5.aspx

Alzheimer’s disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss, progressive cognitive impairment, and various behavioral disturbances. Although the pathological mechanisms underlying Alzheimer’s disease are complex and remain unclear, previous research has identified two widely accepted pathological characteristics: extracellular neuritic plaques containing amyloid beta peptide, and intracellular neurofibrillary tangles containing tau. Furthermore, research has revealed the significant role played by neuroinflammation over recent years. Flavonoids are plant-derived secondary metabolites that possess various bioactivities. Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer’s disease. In this review, we describe the pathogenesis and neuroinflammatory processes of Alzheimer’s disease, and summarize the effects and mechanisms of 13 natural flavonoids (apigenin, luteolin, naringenin, quercetin, morin, kaempferol, fisetin, isoquercitrin, astragalin, rutin, icariin, mangiferin, and anthocyanin) derived from plants or medicinal herbs on neuroinflammation in Alzheimer’s disease.

       Axonal growth inhibitors and their receptors in spinal cord injury: from biology to clinical translationhttps://j...
05/06/2024


Axonal growth inhibitors and their receptors in spinal cord injury: from biology to clinical translation
https://journals.lww.com/nrronline/fulltext/2023/12000/axonal_growth_inhibitors_and_their_receptors_in.4.aspx
Universidade do Porto

Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelin-associated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance...

       Cytokines, synaptic plasticity and network dynamics: a matter of balancehttps://journals.lww.com/nrronline/fullte...
05/06/2024


Cytokines, synaptic plasticity and network dynamics: a matter of balance
https://journals.lww.com/nrronline/fulltext/2023/12000/cytokines,_synaptic_plasticity_and_network.3.aspx
Università degli Studi di Perugia

The modern view of the immune system as a sensitizing and modulating machinery of the central nervous system is now well recognized. However, the specific mechanisms underlying this fine crosstalk have yet to be fully disentangled. To control cognitive function and behavior, the two systems are engaged in a subtle interacting act. In this scenario, a dual action of pro-inflammatory cytokines in the modulation of brain network connections is emerging. Pro-inflammatory cytokines are indeed required to express physiological plasticity in the hippocampal network while being detrimental when over-expressed during uncontrolled inflammatory processes. In this dynamic equilibrium, synaptic functioning and the performance of neural networks are ensured by maintaining an appropriate balance between pro- and anti-inflammatory molecules in the central nervous system microenvironment.

       Repair and regeneration of peripheral nerve injuries that ablate branch pointshttps://journals.lww.com/nrronline/...
05/06/2024


Repair and regeneration of peripheral nerve injuries that ablate branch points
https://journals.lww.com/nrronline/fulltext/2023/12000/repair_and_regeneration_of_peripheral_nerve.2.aspx
University of Wyoming

The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses: (1) the branched anatomy of the peripheral nervous system, (2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed, (3) factors known to influence regeneration through branched nerve structures, (4) techniques and models of branched peripheral nerve injuries in animal models, and (5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.

    The importance of laminin at the blood-brain barrierhttps://journals.lww.com/nrronline/fulltext/2023/12000/the_impor...
05/06/2024


The importance of laminin at the blood-brain barrier
https://journals.lww.com/nrronline/fulltext/2023/12000/the_importance_of_laminin_at_the_blood_brain.1.aspx
San Diego Biomedical Research Institute

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components. The mechanistic basis of this barrier is found at multiple levels, including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes, microglia, and astrocyte endfeet. In addition, extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity, not only by providing an adhesive substrate for blood-brain barrier cells to adhere to, but also by providing guidance cues that strongly influence vascular cell behavior. The extracellular matrix protein laminin is one of the most abundant components of the basement membrane, and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior. In this review, we describe the basic structure of laminin and its receptors, the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states, and most importantly, how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity. Finally, we discuss some of the important unanswered questions in the field and provide a “to-do” list of some of the critical outstanding experiments.

s that tightly bind adjacent endothelial cells and the influence of neighboring pericytes, microglia, and astrocyte endfeet. In addition, extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity, not only by....

         Epigenetic combined with transcriptomic analysis of the m6A methylome after spared nerve injury-induced neuropa...
04/06/2024


Epigenetic combined with transcriptomic analysis of the m6A methylome after spared nerve injury-induced neuropathic pain in mice
https://journals.lww.com/nrronline/fulltext/2023/11000/epigenetic_combined_with_transcriptomic_analysis.40.aspx

Epigenetic changes in the spinal cord play a key role in the initiation and maintenance of nerve injury-induced neuropathic pain. N6-methyladenosine (m6A) is one of the most abundant internal RNA modifications and plays an essential function in gene regulation in many diseases. However, the global m6A modification status of mRNA in the spinal cord at different stages after neuropathic pain is unknown. In this study, we established a neuropathic pain model in mice by preserving the complete sural nerve and only damaging the common peroneal nerve. Our results provide a global landscape of mRNA m6A modifications in the spinal cord in the spared nerve injury model at different stages after injury.

           High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic post-ischemi...
04/06/2024


High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic post-ischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord
https://journals.lww.com/nrronline/fulltext/2023/11000/high_intensity_swimming_alleviates_nociception_and.39.aspx

Physical exercise effectively alleviates chronic pain associated with complex regional pain syndrome type-I. However, the mechanism of exercise-induced analgesia has not been clarified. Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system. However, whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-I has not been demonstrated. In the present study, a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-I and subjected to an intervention involving swimming at different intensities. Chronic pain was reduced only in mice that engaged in high-intensity swimming. The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain, while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23. Finally, shRNA-mediated silencing of chemerin receptor 23 in the spinal cord reversed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammatory polarization of microglia in the dorsal horn of the spinal cord. These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

         Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cel...
04/06/2024


Phosphorylated S6K1 and 4E-BP1 play different roles in constitutively active Rheb-mediated retinal ganglion cell survival and axon regeneration after optic nerve injury
https://journals.lww.com/nrronline/fulltext/2023/11000/phosphorylated_s6k1_and_4e_bp1_play_different.38.aspx

Ras homolog enriched in brain (Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1 (mTORC1). Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR. S6K1 and 4E-BP1 are important downstream effectors of mTORC1. In this study, we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1 in the protection of retinal ganglion cells.

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