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International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605 -
International Journal of Molecular... Mar 2022A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During...
A growing body of studies indicate that small noncoding RNAs, especially microRNAs (miRNA), play a crucial role in response to peripheral nerve injuries. During Wallerian degeneration and regeneration processes, they orchestrate several pathways, in particular the MAPK, AKT, and EGR2 (KROX20) pathways. Certain miRNAs show specific expression profiles upon a nerve lesion correlating with the subsequent nerve regeneration stages such as dedifferentiation and with migration of Schwann cells, uptake of debris, neurite outgrowth and finally remyelination of regenerated axons. This review highlights (a) the specific expression profiles of miRNAs upon a nerve lesion and (b) how miRNAs regulate nerve regeneration by acting on distinct pathways and linked proteins. Shedding light on the role of miRNAs associated with peripheral nerve regeneration will help researchers to better understand the molecular mechanisms and deliver targets for precision medicine.
Topics: Humans; MicroRNAs; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells; Sciatic Nerve
PubMed: 35408800
DOI: 10.3390/ijms23073440 -
Frontiers in Neuroscience 2022Sensory corpuscles, or cutaneous end-organ complexes, are complex structures localized at the periphery of Aβ-axon terminals from primary sensory neurons that primarily...
Sensory corpuscles, or cutaneous end-organ complexes, are complex structures localized at the periphery of Aβ-axon terminals from primary sensory neurons that primarily work as low-threshold mechanoreceptors. Structurally, they consist, in addition to the axons, of non-myelinating Schwann-like cells (terminal glial cells) and endoneurial- and perineurial-related cells. The terminal glial cells are the so-called lamellar cells in Meissner and Pacinian corpuscles. Lamellar cells are variably arranged in sensory corpuscles as a "coin stack" in the Meissner corpuscles or as an "onion bulb" in the Pacinian ones. Nevertheless, the origin and protein profile of the lamellar cells in both morphotypes of sensory corpuscles is quite similar, although it differs in the expression of mechano-gated ion channels as well as in the composition of the extracellular matrix between the cells. The lamellar cells have been regarded as supportive cells playing a passive role in the process of genesis of the action potential, i.e., the mechanotransduction process. However, they express ion channels related to the mechano-electric transduction and show a synapse-like mechanism that suggest neurotransmission at the genesis of the electrical action potential. This review updates the current knowledge about the embryonic origin, development modifications, spatial arrangement, ultrastructural characteristics, and protein profile of the lamellar cells of cutaneous end-organ complexes focusing on Meissner and Pacinian morphotypes.
PubMed: 35356056
DOI: 10.3389/fnins.2022.790130 -
Frontiers in Immunology 2022Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently...
Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially -expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the "snap shot" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.
Topics: Brain; Humans; Multiple Sclerosis; Proteome; Transcriptome; White Matter
PubMed: 35309325
DOI: 10.3389/fimmu.2022.761225 -
Cells Jan 2022Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates...
Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "nerve regeneration", considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.
Topics: Fibrin Tissue Adhesive; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Models, Biological; Nerve Regeneration; Nerve Tissue
PubMed: 35053336
DOI: 10.3390/cells11020221 -
Advances in Ophthalmology Practice and... Dec 2021Magnetic resonance imaging (MRI) plays a significant role in assessing optic neuropathy and providing more detailed information about the lesion of the visual pathway to... (Review)
Review
BACKGROUND
Magnetic resonance imaging (MRI) plays a significant role in assessing optic neuropathy and providing more detailed information about the lesion of the visual pathway to help differentiate optic neuritis from other visual disorders. This study aims to systematically review the literature and verify if there is a real difference in lesion location among different demyelinating optic neuritis (DON) subtypes.
METHODS
A systematic search was conducted including 8 electronic databases and related resources from the establishment of the database to August 25th, 2020. We classified DON into 5 subtypes and divided the visual pathways into five segments mainly comparing the differences in the involved visual pathway sites of different subtypes.
RESULTS
Fifty-five studies were included in the analysis, and the abnormal rate was as high as 92% during the acute phase (within 4 weeks of symptom onset). With respect to lesion location, the orbital segment of the optic nerve was the most frequently involved (87%), whereas optic tract involvement was very rare. Involvement of the orbital segment was more common in myelin oligodendrocyte glycoprotein antibody-related optic neuritis (MOG-ON) (78%) and chronic relapsing inflammatory optic neuropathy (CRION) (81%), while the lesion was found to be located more posteriorly in neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON). With respect to lesion length, approximately 77% of MOG-ON patients had lesions involving more than half of the optic nerve length.
CONCLUSIONS
MRI examination is recommended for DON patients in the acute phase. In MOG-ON, anterior involvement is more common and the involved length is mostly more than 1/2 of the optic nerve length, whereas posterior involvement, intracranial segment, optic chiasm, or optic tract, is more common in NMOSD-ON.
PROSPERO REGISTRATION NUMBER
CRD42020222430 (25-11-2020).
PubMed: 37846325
DOI: 10.1016/j.aopr.2021.100019 -
Brazilian Journal of Otorhinolaryngology 2023The benefit of corticosteroids following facial nerve neurorrhaphy in the setting of complete transection is questionable. This systematic review and meta-analysis aimed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The benefit of corticosteroids following facial nerve neurorrhaphy in the setting of complete transection is questionable. This systematic review and meta-analysis aimed to evaluate corticosteroid efficacy on facial nerve regeneration and functional recovery after complete disruption and neurorrhaphy.
METHODS
Randomized controlled trials on both human and animal models from Ovid MEDLINE and Ovid EMBASE studying corticosteroid efficacy in complete facial nerve disruption followed by neurorrhaphy were included. Data were extracted and pooled for meta-analysis. The outcomes were evaluated from electrophysiology, histology, and functional recovery. However, no randomized controlled trial in human was performed. Possibly, performing human trials with histopathology may not be feasible in clinical setting.
RESULTS
Six animal studies (248 participants) met inclusion criteria. Electrophysiologic outcomes revealed no differences in latency (Standardized Mean Difference (SMD) = -1.97, 95% CI -7.38 to 3.44, p = 0.47) and amplitude (SMD = 0.37, 95% CI -0.44 to 1.18, p = 0.37) between systemic corticosteroids and controls. When analysis compared topical corticosteroid and control, the results provided no differences in latency (Mean Difference (MD) = 0.10, 95% CI -0.04 to 0.24, p = 0.16) and amplitude (SMD = 0.01, 95% CI -0.08 to 0.10, p = 0.81). In histologic outcomes, the results showed no differences in axon diameter (MD = 0.13, 95% CI -0.15 to 0.41, p = 0.37) between systemic corticosteroid and control; however, the result in myelin thickness (MD = 0.06, 95% CI 0.04 to 0.08, p < 0.05) favored control group. When comparing systemic corticosteroid with control in eye blinking, the results favored control (MD = 1.33, 95% CI 0.60 to 2.06, p = 0.0004).
CONCLUSIONS
This evidence did not show potential benefits of systemic or topical corticosteroid deliveries after facial nerve neurorrhaphy in complete transection when evaluating electrophysiologic, histologic, and functional recovery outcomes in animal models.
Topics: Animals; Humans; Facial Nerve; Adrenal Cortex Hormones; Glucocorticoids; Models, Animal; Neurosurgical Procedures
PubMed: 34815200
DOI: 10.1016/j.bjorl.2021.09.005 -
Therapeutic Advances in Neurological... 2021A considerable number of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will experience a relapse, but the effect of maintenance...
BACKGROUND
A considerable number of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will experience a relapse, but the effect of maintenance therapies on re-attack rates is currently unknown.
OBJECTIVE
To investigate the efficacy and safety of immunosuppressive therapy for preventing disease relapses in patients with MOGAD, including rituximab (RTX), mycophenolate mofetil (MMF), and azathioprine (AZA).
METHODS
English-language studies published prior to August 31, 2020, were searched in the NCBI (PubMed), ISI Web of Science, and the Cochrane Library databases. Patient characteristics, treatment regimens, outcome measures, and adverse effects were retrieved.
RESULTS
We enrolled 11 studies in the final meta-analysis, including 346 patients with MOGAD. RTX therapy was demonstrated to result in reduced mean annualized relapse rate (ARR) by 1.35 (95% confidence interval (CI): 0.85-1.85) and reduced mean Expanded Disability Status Scale score by 0.80 (95% CI: 0.53-1.08) in patients with MOGAD. MMF therapy was associated with the mean ARR decreasing by 0.83 (95% CI: 0.31-1.35), and AZA was related to the mean ARR decreasing by 1.71 (95% CI: 0.83-2.58). The reported discontinuation rates of RTX, MMF, and AZA therapy due to adverse effects were 3/197 (1.52%), 3/39 (7.69%), and 4/37 (10.81%), respectively.
CONCLUSION
The study provided evidence to support the efficacy of RTX, MMF, and AZA on the preventive treatment in patients with MOGAD. However, large randomized controlled trials are still needed in the future.
PubMed: 34790259
DOI: 10.1177/17562864211054157 -
Neurology(R) Neuroimmunology &... Jan 2022The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with clinical response to immunotherapy in patients with anti-MAG neuropathy.
METHODS
As of January 29, 2020, we used anti-myelin-associated glycoprotein-related search strings in the Medline database to identify studies that provided information on anti-MAG immunoglobulin M (IgM) autoantibodies and clinical outcomes during immunotherapies. The relative change in anti-MAG IgM titers, paraprotein levels, or total IgM was determined before, during, or posttreatment, and the patients were assigned to "responder," "nonresponder,"' or "acute deteriorating" category depending on their clinical response to treatment. The studies were qualified as "supportive" or "not supportive" depending on the percentage of patients exhibiting an association between relative change of anti-MAG antibody titers or levels and change in clinical outcomes.
RESULTS
Fifty studies with 410 patients with anti-MAG neuropathy were included in the analysis. Forty studies with 303 patients supported the hypothesis that a "responder" patient had a relative reduction of anti-MAG antibody titers or levels that is associated with clinical improvements and "nonresponder" patients exhibited no significant change in anti-MAG IgM antibodies. Six studies with 93 patients partly supported, and 4 studies with 26 patients did not support the hypothesis.
DISCUSSION
The retrospective analysis confirmed the hypothesis that a relative reduction in serum anti-MAG IgM antibodies is associated with a clinical response to immunotherapies; a sustained reduction of at least 50% compared with pretreatment titers or levels could be a valuable indicator for therapeutic response.
Topics: Aged; Autoantibodies; Autoimmune Diseases of the Nervous System; Female; Humans; Immunologic Factors; Male; Middle Aged; Myelin-Associated Glycoprotein; Retrospective Studies
PubMed: 34759022
DOI: 10.1212/NXI.0000000000001109 -
Frontiers in Neurology 2021Coexisting anti-NMDAR and MOG antibody (anti-NMDAR-IgG/MOG-IgG)-associated encephalitis have garnered great attention. This study aimed to perform a secondary analysis...
Coexisting anti-NMDAR and MOG antibody (anti-NMDAR-IgG/MOG-IgG)-associated encephalitis have garnered great attention. This study aimed to perform a secondary analysis to determine the clinical features of this disease. We searched several databases for related publications published prior to April 2021. A pooled analysis was conducted with the fixed-effects model using the Mante-Haenszel method ( ≤ 50%), or the random-effects model computed by the DerSimonian-Laird method ( > 50%). Stata software (version 15.0 SE) was used for the analyses. Nine observational studies and 16 case reports (58 cases with anti-NMDAR-IgG/MOG-IgG, 21.0 [8.5, 29.0] years, male 58.6%) were included. The incidences (95%CI) of anti-NMDAR-IgG/MOG-IgG in the patients with serum MOG-IgG and CSF anti-NMDAR-IgG were 0.09 (0.02-0.19) and 0.07 (0.01-0.19), respectively. The median [IQR] of CSF anti-NMDAR antibody titer was 32 [10, 100], and the serum anti-MOG antibody titer was 100 [32, 320]. The prominent clinical symptoms were encephalitic manifestations, including seizures (56.9%) and abnormal behavior (51.7%), rather than demyelinating manifestations, such as speech disorder (34.5%) and optic neuritis (27.6%). Relapse occurred in 63.4% of anti-NMDAR-IgG/MOG-IgG patients, in whom 50.0% of cases relapsed with encephalitic manifestations, and 53.8% relapsed with demyelinating manifestations. The common MRI changes were in the cortex or subcortex (70.7%) and brainstem (31.0%). 31.3% of patients presented with unilateral cerebral cortical encephalitis with epilepsy and 12.5% displayed bilateral frontal cerebral cortex encephalitis. Anti-NMDAR-IgG/MOG-IgG patients showed more frequent mental behavior (OR, 95%CI, 68.38, 1.36-3,434.37), involuntary movement (57.86, 2.53-1,325.11), sleep disorders (195.00, 7.07-5,380.15), and leptomeninge lesions (7.32, 1.81-29.58), and less frequent optic neuritis (0.27, 0.09-0.83) compared to anti-NMDAR-IgG/MOG-IgG patients and presented more common relapse (5.63, 1.75-18.09), preceding infection (2.69, 1.03-7.02), subcortical lesions (116.60, 4.89-2,782.09), basal ganglia lesions (68.14, 2.99-1,554.27), brainstem lesions (24.09, 1.01-574.81), and spinal cord lesions (24.09, 1.01-574.81) compared to anti-NMDAR-IgG/MOG-IgG. In conclusion, anti-NMDAR-IgG/MOG-IgG was rarely observed, but the incidence rate of relapse was very high. The overall symptoms seemed to be similar to those of NMDAR encephalitis.
PubMed: 34512521
DOI: 10.3389/fneur.2021.711376