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1.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360964

RESUMO

GPR39, a member of the ghrelin family of G protein-coupled receptors, is zinc-responsive and contributes to the regulation of diverse neurovascular and neurologic functions. Accumulating evidence suggests a role as a homeostatic regulator of neuronal excitability, vascular tone, and the immune response. We review GPR39 structure, function, and signaling, including constitutive activity and biased signaling, and summarize its expression pattern in the central nervous system. We further discuss its recognized role in neurovascular, neurological, and neuropsychiatric disorders.


Assuntos
Doenças Cardiovasculares/genética , Doenças do Sistema Nervoso/genética , Acoplamento Neurovascular , Receptores Acoplados a Proteínas G/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Homeostase , Humanos , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais
2.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445124

RESUMO

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.


Assuntos
Neurônios GABAérgicos/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Núcleo Accumbens/fisiopatologia , Neuralgia do Trigêmeo/fisiopatologia , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Feminino , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Maxila/inervação , Doenças do Sistema Nervoso/metabolismo , Núcleo Accumbens/metabolismo , Optogenética/métodos , Ratos , Ratos Sprague-Dawley , Recompensa , Tálamo/metabolismo , Neuralgia do Trigêmeo/metabolismo
3.
Rev Bras Ter Intensiva ; 33(2): 325, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34231815

RESUMO

COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020. The clinical presentation is predominantly respiratory symptoms; however, in the current literature, several neurological manifestations associated with SARS-CoV-2 infection have been described. The authors present the clinical case of a 45-year-old man hospitalized for pneumonia with a positive test result for SARS-CoV-2, without a neurological history, who, on the sixteenth day of hospitalization, presented a sudden change in his state of consciousness accompanied by conjugated right gaze deviation and myoclonus of the face and thoracic region to the left, followed by generalized tonic-clonic seizures associated with persistent left hemiparesis. The present study highlights a positive RT-PCR test for SARS-CoV-2 in cerebrospinal fluid. The patient progressed with gradual improvement, and the outcome was favorable.


Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/virologia , SARS-CoV-2/isolamento & purificação , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/diagnóstico , Convulsões/virologia
4.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299111

RESUMO

The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.


Assuntos
Sistema Glinfático/fisiopatologia , Inflamação/patologia , Doenças do Sistema Nervoso/fisiopatologia , Animais , Humanos
5.
Pan Afr Med J ; 38: 326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285749

RESUMO

Introduction: although the main manifestations of COVID-19 are respiratory, several neurological symptoms and complications have also been reported. The pandemic seems to have some epidemiological specificities in sub-Saharan Africa, and this may be reflected in the type and frequency of neurological symptoms. This study aimed to report neurological manifestations associated with symptomatic COVID-19 in a sub-Saharan African setting. Methods: we conducted a retrospective review of symptomatic PCR-confirmed COVID-19 cases admitted to the Bafoussam Regional Hospital between March and September 2020. Patients' files were reviewed at discharge by a consultant neurologist. Socio-demographic characteristics, co-morbidities, symptoms on admission, neurological symptoms during hospitalization, management, and in-hospital outcome were recorded. Comparisons between patients with and without neurological symptoms were performed using Fisher's exact and Mann-Whitney U test. Results: we enrolled 177 symptomatic patients (68% men). Mean age was 54.6 ± 17.8 years (range 2-99 years). Co-morbidities were present in 57.6% of patients, including hypertension (27.1%) and diabetes mellitus (25.4%). Neurological symptoms were found in 113 (63.8%) patients. The most frequent were headache (39.0%), myalgia (35.6%), anosmia (11.9%), impaired consciousness (10.7%) and delirium (5.6%). Regarding the presenting symptoms, fever was more frequent in patients with neurological symptoms than in those without (81.4% versus 50.0%, p< 0.001), while digestive symptoms were less frequent in patients with neurological symptoms (0.9% versus 9.4%, p= 0.004). Conclusion: neurological manifestations are frequent and heterogeneous in patients with symptomatic COVID-19. Further studies are needed to clarify the pathophysiology of neurological symptoms in COVID-19 and their impact on patients' long-term outcome.


Assuntos
COVID-19/complicações , Hospitalização , Doenças do Sistema Nervoso/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Camarões , Criança , Pré-Escolar , Comorbidade , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/fisiopatologia , Estudos Retrospectivos , Adulto Jovem
6.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068881

RESUMO

Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer's disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5' triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain. Herein, we review the emerging evidence that directly implicates Panx-1 channels in the neuroinflammatory response in the CNS.


Assuntos
Conexinas/metabolismo , Inflamação/fisiopatologia , Proteínas do Tecido Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Animais , Humanos , Inflamação/metabolismo , Doenças do Sistema Nervoso/metabolismo
7.
Neurotox Res ; 39(5): 1613-1629, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34169404

RESUMO

Aside from the respiratory distress as the predominant clinical presentation of SARS-CoV-2 infection, various neurological complications have been reported with the infection during the ongoing pandemic, some of which cause serious morbidity and mortality. Herein, we gather the latest anatomical evidence of the virus's presence within the central nervous system. We then delve into the possible SARS-CoV-2 entry routes into the neurological tissues, with the hematogenous and the neuronal routes as the two utmost passage routes into the nervous system. We then give a comprehensive review of the neurological manifestations of the SARS-CoV-2 invasion in both the central and peripheral nervous system and its underlying pathophysiology via investigating large studies in the field and case reports in cases of study scarcity.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , COVID-19/virologia , Sistema Nervoso Central/virologia , Humanos , Doenças do Sistema Nervoso/virologia , Sistema Nervoso Periférico/virologia
9.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064670

RESUMO

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Fármacos Neuroprotetores/uso terapêutico , Transmissão Sináptica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Transmissão Sináptica/efeitos dos fármacos
10.
NeuroRehabilitation ; 48(4): 441-449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967068

RESUMO

BACKGROUND: Patients with neurological disorders can present the weakness of respiratory muscle and impaired cough function. Previous studies have shown that respiratory muscle strength training (RMT) is an effective method of improving the strength of respiratory muscle. The effects of RMT on cough function remain controversial. OBJECTIVE: We aimed to analyze randomized controlled trials (RCTs) that investigated the effects of RMT on cough function of patients with neurological disorders. METHODS: Pubmed, Medline, Embase, and the Cochrane Library were searched electronically for RCTs. Two reviewers independently performed data extraction and quality assessment. Data were analyzed by using RevMan 5.3 software of The Cochrane Collaboration. RESULTS: Five studies with 185 participants were included. The mean PEDro score was 6.2 (range 5 to 7), showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training improved peak expiratory cough flow of voluntary cough by 2.16 (95% CI 1.16 to 3.17) and involuntary cough by 2.84 (95% CI 1.29 to 4.39), with statistical significance (P < 0.0001, P = 0.0003). The experimental group had an improvement of 0.19 cmH2O (95% CI -0.12 to 0.5) on the maximal inspiratory pressure, 0.09 cmH2O (95% CI -0.23 to 0.42) on the maximal expiratory pressure, but with no statistical significance (P = 0.23, P = 0.58) between groups. CONCLUSION: Respiratory muscle training was considered as an effective method for improving cough function. However, this review was insufficient to conclude whether respiratory muscle training was effective in improving inspiratory and expiratory muscle strength, this was opposite with previous meta-analysis. These effects might due to the small samples and different diseases.


Assuntos
Exercícios Respiratórios/métodos , Tosse/prevenção & controle , Doenças do Sistema Nervoso/fisiopatologia , Reabilitação Neurológica/métodos , Tosse/fisiopatologia , Expiração , Humanos , Força Muscular , Ensaios Clínicos Controlados Aleatórios como Assunto , Músculos Respiratórios/fisiologia
11.
J Clin Neurosci ; 88: 219-225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992187

RESUMO

Study design Literature review. OBJECTIVES: Describe the implications of post-COVID syndrome due to neurological sequelae including treatment and the differences that may exist between this group of patients and those who present these events not associated with COVID-19. METHODS: A non-systematic review of the literature was carried out in PubMed and Science Direct databases, using the keywords "Post-acute COVID-19 syndrome"; "Neurological complications"; "Neurologic Manifestations" "COVID-19″ and "Rehabilitation", as well as synonyms, which were combined with the operators "AND" and "OR". RESULTS: The COVID-19 viral caustive agent, SARS-CoV-2, has a high affinity for human angiotensin-converting enzyme 2 receptor on type II pneumocytes. This receptor is also expressed in neurons and glial cells. Based on the foregoing and other not so clear mechanisms, it is stated that SARS-CoV-2 has tropism for the nervous system, being evident through the neurological manifestations observed in patients with mild, moderate and severe phenotype of the disease such as anosmia, ageusia, headache, cerebrovascular accidents, Guillain-Barré syndrome, seizures, and encephalopathy. This can generate severe sequelae and even fatal outcomes in those affected. CONCLUSIONS: Neurological complications caused by COVID-19 are frequent and represent a risk that compromises the functional capacity and the life of patients. The suspicion of these conditions, the strict control of metabolic alterations and cardiovascular risk factors, the effective and safe treatment of these entities, are a current challenge throughout the pandemic. The rehabilitation process in these patients is a challenge. This is due to the limitations generated by multi-organ damage, as well as risk of brain death.


Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Humanos , Doenças do Sistema Nervoso/reabilitação , Síndrome
12.
Front Immunol ; 12: 653786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33981305

RESUMO

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/complicações , Mielite Transversa/complicações , SARS-CoV-2/patogenicidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielite Transversa/diagnóstico , Mielite Transversa/patologia , Mielite Transversa/fisiopatologia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Tropismo Viral , Adulto Jovem
13.
Best Pract Res Clin Anaesthesiol ; 35(2): 207-220, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34030805

RESUMO

Neuropatients often require invasive mechanical ventilation (MV). Ideal ventilator settings and respiratory targets in neuro patients are unclear. Current knowledge suggests maintaining protective tidal volumes of 6-8 ml/kg of predicted body weight in neuropatients. This approach may reduce the rate of pulmonary complications, although it cannot be easily applied in a neuro setting due to the need for special care to minimize the risk of secondary brain damage. Additionally, the weaning process from MV is particularly challenging in these patients who cannot control the brain respiratory patterns and protect airways from aspiration. Indeed, extubation failure in neuropatients is very high, while tracheostomy is needed in one-third of the patients. The aim of this manuscript is to review and describe the current management of invasive MV, weaning, and tracheostomy for the main four subpopulations of neuro patients: traumatic brain injury, acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage.


Assuntos
Manuseio das Vias Aéreas/métodos , Cuidados Críticos/métodos , Intubação Intratraqueal/métodos , Doenças do Sistema Nervoso/terapia , Respiração Artificial/métodos , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Volume de Ventilação Pulmonar/fisiologia
14.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925434

RESUMO

The investigation of synaptic functions remains one of the most fascinating challenges in the field of neuroscience and a large number of experimental methods have been tuned to dissect the mechanisms taking part in the neurotransmission process. Furthermore, the understanding of the insights of neurological disorders originating from alterations in neurotransmission often requires the development of (i) animal models of pathologies, (ii) invasive tools and (iii) targeted pharmacological approaches. In the last decades, additional tools to explore neurological diseases have been provided to the scientific community. A wide range of computational models in fact have been developed to explore the alterations of the mechanisms involved in neurotransmission following the emergence of neurological pathologies. Here, we review some of the advancements in the development of computational methods employed to investigate neuronal circuits with a particular focus on the application to the most diffuse neurological disorders.


Assuntos
Modelos Neurológicos , Doenças do Sistema Nervoso/etiologia , Transmissão Sináptica/fisiologia , Doença de Alzheimer/etiologia , Animais , Dendritos/fisiologia , Epilepsia/etiologia , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Doença de Parkinson/etiologia , Esquizofrenia/etiologia , Sinapses/fisiologia
15.
Mar Drugs ; 19(4)2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916730

RESUMO

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Anti-Inflamatórios/farmacocinética , Humanos , Degeneração Neural , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/patologia , Fármacos Neuroprotetores/farmacocinética , Xantofilas/farmacocinética , Xantofilas/farmacologia
16.
Clin Drug Investig ; 41(6): 513-527, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33886098

RESUMO

Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. It is required for the conversion of oxidised glutathione to the reduced form and for the mitochondrial respiratory chain as complexes I and II contain flavoprotein reductases and electron transferring flavoproteins. Riboflavin deficiency has been demonstrated to impair the oxidative state of the body, especially in relation to lipid peroxidation status, in both animal and human studies. In the nervous system, riboflavin is essential for the synthesis of myelin and its deficiency can determine the disruption of myelin lamellae. The inherited condition of restricted riboflavin absorption and utilisation, reported in about 10-15% of world population, warrants further investigation in relation to its association with the main neurodegenerative diseases. Several successful trials testing riboflavin for migraine prevention were performed, and this drug is currently classified as a Level B medication for migraine according to the American Academy of Neurology evidence-based rating, with evidence supporting its efficacy. Brown-Vialetto-Van Laere syndrome and Fazio-Londe diseases are now renamed as "riboflavin transporter deficiency" because these are autosomal recessive diseases caused by mutations of SLC52A2 and SLC52A3 genes that encode riboflavin transporters. High doses of riboflavin represent the mainstay of the therapy of these diseases and high doses of riboflavin should be rapidly started as soon as the diagnosis is suspected and continued lifelong. Remarkably, some mitochondrial diseases respond to supplementation with riboflavin. These include multiple acyl-CoA-dehydrogenase deficiency (which is caused by ETFDH gene mutations in the majority of the cases, or mutations in the ETFA and ETFB genes in a minority), mutations of ACAD9 gene, mutations of AIFM1 gene, mutations of the NDUFV1 and NDUFV2 genes. Therapeutic riboflavin administration has been tried in other neurological diseases, including stroke, multiple sclerosis, Friedreich's ataxia and Parkinson's disease. Unfortunately, the design of these clinical trials was not uniform, not allowing to accurately assess the real effects of this molecule on the disease course. In this review we analyse the properties of riboflavin and its possible effects on the pathogenesis of different neurological diseases, and we will review the current indications of this vitamin as a therapeutic intervention in neurology.


Assuntos
Doenças do Sistema Nervoso/tratamento farmacológico , Riboflavina/uso terapêutico , Animais , Paralisia Bulbar Progressiva/tratamento farmacológico , Paralisia Bulbar Progressiva/genética , Flavoproteínas Transferidoras de Elétrons/genética , Perda Auditiva Neurossensorial/tratamento farmacológico , Humanos , Proteínas de Membrana Transportadoras/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação , Doenças do Sistema Nervoso/fisiopatologia , Riboflavina/metabolismo
17.
Int J Mol Sci ; 22(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800600

RESUMO

Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression-edema-ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat's sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.


Assuntos
Hidrogéis/química , Síndromes de Compressão Nervosa/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Poliésteres , Polietilenoglicóis , Nervo Isquiático/efeitos dos fármacos , Ondas Ultrassônicas , Animais , Síndrome do Túnel Carpal/fisiopatologia , Força Compressiva , Modelos Animais de Doenças , Edema , Masculino , Bainha de Mielina/química , Síndromes de Compressão Nervosa/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/patologia
18.
Mar Drugs ; 19(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808737

RESUMO

In recent decades, several neuroprotective agents have been provided in combating neuronal dysfunctions; however, no effective treatment has been found towards the complete eradication of neurodegenerative diseases. From the pathophysiological point of view, growing studies are indicating a bidirectional relationship between gut and brain termed gut-brain axis in the context of health/disease. Revealing the gut-brain axis has survived new hopes in the prevention, management, and treatment of neurodegenerative diseases. Accordingly, introducing novel alternative therapies in regulating the gut-brain axis seems to be an emerging concept to pave the road in fighting neurodegenerative diseases. Growing studies have developed marine-derived natural products as hopeful candidates in a simultaneous targeting of gut-brain dysregulated mediators towards neuroprotection. Of marine natural products, carotenoids (e.g., fucoxanthin, and astaxanthin), phytosterols (e.g., fucosterol), polysaccharides (e.g., fucoidan, chitosan, alginate, and laminarin), macrolactins (e.g., macrolactin A), diterpenes (e.g., lobocrasol, excavatolide B, and crassumol E) and sesquiterpenes (e.g., zonarol) have shown to be promising candidates in modulating gut-brain axis. The aforementioned marine natural products are potential regulators of inflammatory, apoptotic, and oxidative stress mediators towards a bidirectional regulation of the gut-brain axis. The present study aims at describing the gut-brain axis, the importance of gut microbiota in neurological diseases, as well as the modulatory role of marine natural products towards neuroprotection.


Assuntos
Organismos Aquáticos/metabolismo , Bactérias/metabolismo , Produtos Biológicos/farmacologia , Encéfalo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Doenças do Sistema Nervoso/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Animais , Produtos Biológicos/isolamento & purificação , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Disbiose , Humanos , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/fisiopatologia , Fármacos Neuroprotetores/isolamento & purificação
19.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33857435

RESUMO

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Tosse/etiologia , Inflamação/etiologia , Doenças do Sistema Nervoso/etiologia , Neuroimunomodulação , Tosse/fisiopatologia , Humanos , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , SARS-CoV-2 , Síndrome
20.
Pan Afr Med J ; 38: 111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912281

RESUMO

Millions of patients, with suspected complex neurogenetic disorders, living in resource limited regions around the world have no access to genetic testing despite the rapidly expanding availability and decreasing costs of genetic testing in first world nations. The barriers to increasing availability of genetic testing in resource limited nations are multifactorial but can be attributed, in large part, to a lack of awareness of the power of genetic testing to lead to a rapid, cost-effective, diagnosis that potentially will have profound clinical implications on treatment and patient outcomes. We report our experience with whole exome sequencing (WES) done for the first time in 5 patients of African descent with a suspected neurogenetic disorder living in a resource limited setting on the Eastern Caribbean island of Barbados. A diagnostic pathogenic mutation was found in 3 patients in the SCN1A, STXBP1 and SCN4A, who clinically were diagnosed with Dravet syndrome, Lennox-Gastaut syndrome, paramytonia and seizures respectively. A variant of undetermined significance was found in a patient with global developmental delays, hypotonia, with abnormal eye movements. In one patient WES was non-diagnostic. This result highlights the high yield of WES in carefully selected patients with a neurologic disease and the need for increase access to genetic testing in resource limited settings globally.


Assuntos
Testes Genéticos/métodos , Doenças do Sistema Nervoso/diagnóstico , Sequenciamento Completo do Exoma/métodos , Adulto , Barbados , Criança , Análise Custo-Benefício , Testes Genéticos/economia , Humanos , Lactente , Proteínas Munc18/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/fisiopatologia , Sequenciamento Completo do Exoma/economia , Adulto Jovem
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