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Journal of Toxicology and Environmental... May 2022Studies of nervous system effects of glyphosate, a widely used herbicide, have not been critically examined. The aim of this paper was to systematically review...
Studies of nervous system effects of glyphosate, a widely used herbicide, have not been critically examined. The aim of this paper was to systematically review glyphosate-induced neurotoxicity literature to determine its usefulness in regulatory decision-making. The review was restricted to mammalian studies of behavior, neuropathology, and neuropharmacology; and other biochemical studies were considered supplementary information. Glyphosate formulation studies were also considered, despite uncertainties regarding toxicities of the formulated products; no studies used a formulation vehicle as the control. Inclusion criteria were developed to ensure consistent evaluation of studies, and investigations were also ranked using ToxRTool software to determine reliability. There were 27 studies (open literature and available regulatory reports), but 11 studies were considered unreliable (mostly due to critical methodological deficiencies). There were only seven acceptable investigations on glyphosate alone. Studies differed in terms of dosing scenarios, experimental designs, test species, and commercial product. Limitations included using only one dose and/or one test time, small sample sizes, limited data presentation, and/or overtly toxic doses. While motor activity was the most consistently affected endpoint (10 of 12 studies), there were considerable differences in outcomes. In six investigations, there were no marked neuropathological changes in the central or peripheral nervous system. Other neurological effects were less consistent, and some outcomes were less convincing due to influences including high variability and small effect sizes. Taken together, these studies do not demonstrate a consistent impact of glyphosate on the structure or function of the mammalian nervous system.
Topics: Animals; Glycine; Herbicides; Mammals; Reproducibility of Results; Glyphosate
PubMed: 35676826
DOI: 10.1080/10937404.2022.2083739 -
Frontiers in Neurology 2020Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from...
Within the neurovascular unit (NVU), the blood-brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.
PubMed: 33613412
DOI: 10.3389/fneur.2020.577312 -
Pain and Therapy Jun 2021Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable... (Review)
Review
INTRODUCTION
Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN).
METHODS
A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review.
RESULTS
The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN.
DISCUSSION
Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.
PubMed: 33145709
DOI: 10.1007/s40122-020-00210-3 -
Neurologia 2021This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic... (Review)
Review
INTRODUCTION
This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache.
DEVELOPMENT
Various medical databases were used to perform a systematic review of the scientific literature. The search for articles continued until 31 October 2016, and included clinical trials, systematic reviews and/or meta-analyses, health technology assessment reports, and clinical practice guidelines that included measurements of efficiency/effectiveness or adverse effects associated with the treatment. The review excluded cohort studies, case-control studies, case series, literature reviews, letters to the editor, opinion pieces, editorials, and studies that had been duplicated or outdated by later publications from the same institution. Regarding effectiveness, we found that SPG stimulation had positive results for pain relief, attack frequency, medication use, and patients' quality of life. In the results regarding safety, we found a significant number of adverse events in the first 30 days following the intervention. Removal of the device was necessary in some patients. Little follow-up data, and no long-term data, is available.
CONCLUSIONS
These results are promising, despite the limited evidence available. We consider it essential for research to continue into the safety and efficacy of SPG stimulation for patients with refractory chronic cluster headache. In cases where this intervention may be indicated, treatment should be closely monitored.
Topics: Cluster Headache; Cohort Studies; Electric Stimulation Therapy; Ganglia, Parasympathetic; Humans; Quality of Life
PubMed: 34238527
DOI: 10.1016/j.nrleng.2017.11.002 -
BMJ Open Ophthalmology Nov 2023To explore the current research about the role of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in dysthyroid optic neuropathy... (Meta-Analysis)
Meta-Analysis
PURPOSE
To explore the current research about the role of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in dysthyroid optic neuropathy (DON).
METHODS
Studies in the literature that focused on OCT, OCTA and DON were retrieved by searching PubMed, EMBASE, Cochrane databases and Clinical Trial before 20 June 2023. The methodological quality was assessed using the Newcastle-Ottawa scale. The quantitative calculation was performed using Review Manager V.5.3.
RESULTS
Twelve studies met the eligibility criteria and were included. DON group presented lower macular ganglion cell complex in the overall, superior and inferior hemifields compared with the non-DON group. Furthermore, the ganglion cell layer and inner plexiform layer in DON group was thinner in contrast to the non-DON group. The optic nerve head vessel density was lower in the DON group than that in the non-DON group. A reduction of radial peripapillary capillary vessel density could be seen in the DON group than the non-DON group in overall, inside disc, peripapillary, superior-hemifield, temporal and nasal. Besides, the macular superficial retinal capillary layer of non-DON and DON is lower than the healthy control group.
CONCLUSIONS
This study supported the potential value of OCT and OCTA metrics as novel biomarkers of DON. Ophthalmologists should comprehensively consider the retinal structure and microvasculature in dealing with DON.
ETHICS AND DISSEMINATION
This systematic review included data from published literature and was exempt from ethics approval. Results would be disseminated through peer-reviewed publication and presented at academic conferences engaging clinicians.
PROSPERO REGISTRATION NUMBER
CRD42023414907.
Topics: Humans; Tomography, Optical Coherence; Optic Disk; Angiography; Retinal Ganglion Cells; Optic Nerve Diseases
PubMed: 37996119
DOI: 10.1136/bmjophth-2023-001379 -
Annals of Medicine 2023Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac... (Review)
Review
BACKGROUND
Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac sympathetic hyperinnervation remain underexposed.
OBJECTIVE
To provide a systematic review on cardiac sympathetic hyperinnervation after MI, taking into account: (1) definition, experimental model and quantification method and (2) location, amount and timing, in order to obtain an overview of current knowledge and to expose gaps in literature.
METHODS
References on cardiac sympathetic hyperinnervation were screened for inclusion. The included studies received a full-text review and quality appraisal. Relevant data on hyperinnervation were collected and qualitatively analysed.
RESULTS
Our literature search identified 60 eligible studies performed between 2000 and 2022. Cardiac hyperinnervation is generally defined as an increased sympathetic nerve density or increased number of nerves compared to another control group (100%). Studies were performed in a multitude of experimental models, but most commonly in male rats with permanent left anterior descending (LAD) artery ligation (male: 63%, rat: 68%, permanent ligation: 93%, LAD: 97%). Hyperinnervation seems to occur mainly in the borderzone. Quantification after MI was performed in regions of interest in µm/mm (41%) or in percentage of nerve fibres (46%) and the reported amount showed a great variation ranging from 439 to 126,718 µm/mm. Hyperinnervation seems to start from three days onwards to >3 months without an evident peak, although studies on structural evaluation over time and in the chronic phase were scarce.
CONCLUSIONS
Cardiac sympathetic hyperinnervation after MI occurs mainly in the borderzone from three days onwards and remains present at later timepoints, for at least 3 months. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to differential quantification methods. Further studies are required that evaluate cardiac sympathetic hyperinnervation over time and in the chronic phase, in transmural sections, in the female sex, and in MI with reperfusion.
Topics: Male; Female; Rats; Humans; Animals; Heart; Myocardial Infarction; Arrhythmias, Cardiac; Sympathetic Nervous System; Death, Sudden, Cardiac
PubMed: 38065671
DOI: 10.1080/07853890.2023.2283195 -
Frontiers in Cellular Neuroscience 2023It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can...
It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can be described as an inflammatory response, within the CNS, mediated through several cytokines, reactive oxygen species, chemokines and other inflammatory markers. These inflammatory players, in particular cytokines, play important roles. Several studies have demonstrated that psychostimulants impact on cytokine production and release, both centrally and at the peripheral level. Nevertheless, the available data is often contradictory. Because understanding how cytokines are modulated by psychoactive substances seems crucial to perspective successful therapeutic interventions, here, we conducted a scoping review of the available literature. We have focused on how different psychostimulants impact on the cytokine profile. Publications were grouped according to the substance addressed (methamphetamine, cocaine, methylphenidate, MDMA or other amphetamines), the type of exposure and period of evaluation (acute, short- or long-term exposure, withdrawal, and reinstatement). Studies were further divided in those addressing central cytokines, circulating (peripheral) levels, or both. Our analysis showed that the classical pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were those more investigated. The majority of studies have reported increased levels of these cytokines in the central nervous system after acute or repeated drug. However, studies investigating cytokine levels during withdrawal or reinstatement have shown higher variability in their findings. Although we have identified fewer studies addressing circulating cytokines in humans, the available data suggest that the results may be more robust in animal models than in patients with problematic drug use. As a major conclusion, an extensive use of arrays for relevant cytokines should be considered to better determine which cytokines, upon the classical ones, may be involved in the progression from episodic use to the development of addiction. A concerted effort is still necessary to address the link between peripheral and central immune players, including from a longitudinal perspective. Until there, the identification of new biomarkers and therapeutic targets to envision personalized immune-based therapeutics will continue to be unlikely.
PubMed: 37305435
DOI: 10.3389/fncel.2023.1109611 -
Neurology(R) Neuroimmunology &... Jan 2023To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic...
BACKGROUND AND OBJECTIVES
To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.
METHODS
Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015-2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018-2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.
RESULTS
Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44-76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5-18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, = 0.02) and limbic (54% vs 14%, < 0.01), brainstem (27% vs 5%, = 0.02), and dorsal root ganglia (45% vs 5%, < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, < 0.01) and higher mortality (91% vs 46%, < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, < 0.01) and higher mortality (26%, < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.
DISCUSSION
The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.
Topics: Humans; Male; Female; Immune Checkpoint Inhibitors; Drug-Related Side Effects and Adverse Reactions; Peripheral Nervous System; Antibodies, Antinuclear; Lung Neoplasms
PubMed: 36446613
DOI: 10.1212/NXI.0000000000200058 -
International Journal of Environmental... Jan 2022Inferior alveolar nerve (IAN) block injections are commonly used in clinical practice, but they are not free from complications. The aim of the present systematic review... (Review)
Review
Inferior alveolar nerve (IAN) block injections are commonly used in clinical practice, but they are not free from complications. The aim of the present systematic review is to assess the nerve-related adverse effects of IAN block anesthesia. A structured and systematic search was performed on the major electronic databases (PubMed, Cochrane Library, Web of Science, Scopus and CINAHL) for studies published in English until 30 September 2021. A total of 131 articles were identified through database searching using combinations of keywords. Fifteen papers were included and assessed for eligibility. Overall, nerve damage following an IAN block anesthesia injection is a rare occurrence, probably due to the direct nerve trauma of the needle, a neurotoxic effect of the used anesthetic solution and/or a combination of them. From a medico-legal point of view, a balanced discussion prior to nerve block anesthesia should be pursued in order to avoid patients' reluctance to undergo necessary dental treatment due to the remote eventuality of nerve injury.
Topics: Anesthetics, Local; Humans; Injections; Mandible; Mandibular Nerve; Nerve Block
PubMed: 35162650
DOI: 10.3390/ijerph19031627 -
Diagnostics (Basel, Switzerland) Jan 2021Neuropathic pain is an injury or disease of the central and/or peripheral somatosensory nervous system, and it has a significant impact on quality of life, especially... (Review)
Review
BACKGROUND
Neuropathic pain is an injury or disease of the central and/or peripheral somatosensory nervous system, and it has a significant impact on quality of life, especially since it is often refractory to treatment. Rehabilitative intervention is considered in various guidelines on neuropathic pain treatment, although not in an organic nor detailed way. The aim of this systematic review was to analyze the most indicated therapeutic strategies, providing rehabilitative recommendations in the management of neuropathic pain.
METHODS
A systematic review was performed according to PRISMA guidelines. The scientific search, carried out until July 2020, considered guidelines in English language of the last thirteen years.
RESULTS
Six guidelines were analyzed, from which emerges that a multidisciplinary approach, comprehensive of pharmacologic and nonpharmacologic interventions, should drive neuropathic pain management. A relevant role in non-pharmacological intervention is played by rehabilitation, through an adequate tailored rehabilitation program and physical therapies.
CONCLUSION
This analysis highlights the importance of rehabilitation but also the lack of evidence on various rehabilitative practices. Arises hence the need for further studies in this field to better define a rehabilitative treatment strategy.
PubMed: 33466426
DOI: 10.3390/diagnostics11010074