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The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.

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Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them.

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Tissue exposure to high levels of tyrosine, which is characteristic of an inborn error of metabolism named Tyrosinemia, is related to severe symptoms, including neurological alterations. The clinical manifestations and pathogenesis of tyrosine neurotoxicity can be recapitulated in experimental models in vivo and in vitro. A widely used experimental model to study brain tyrosine damage is the chronic and acute administration of this amino acid in infant rats. Other research groups and we have extensively studied the pathogenic events in the brain structures of rats exposed to high tyrosine levels. Rats administered acutely and chronically with tyrosine presented decreased and inhibition of the essential metabolism enzymes, e.g., Krebs cycle enzymes and mitochondrial respiratory complexes in the brain structures. These alterations induced by tyrosine toxicity were associated with brain oxidative stress, astrocytes, and, ultimately, cognitive impairments. Notably, in vivo data were corroborated by in vitro studies using cerebral regions homogenates incubated with tyrosine excess. Considering metabolism's importance to brain functioning, we hypothesized that mitochondrial and metabolic dysfunctions are closely related to neurological alterations induced by tyrosine neurotoxicity. Herein, we reviewed the main mechanisms associated with tyrosine neurotoxicity in experimental models, emphasizing the role of mitochondrial dysfunction.

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The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

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Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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In late December 2019, multiple atypical pneumonia cases resulted in severe acute respiratory syndrome caused by a pathogen identified as a novel coronavirus SARS-CoV-2. The most common coronavirus disease 2019 (COVID-19) symptoms are pneumonia, fever, dry cough, and fatigue. However, some neurological complications following SARS-CoV-2 infection include confusion, cerebrovascular diseases, ataxia, hypogeusia, hyposmia, neuralgia, and seizures. Indeed, a growing literature demonstrates that neurotropism is a common feature of coronaviruses; therefore, the infection mechanisms already described in other coronaviruses may also be applicable for SARS-CoV-2. Understanding the underlying pathogenetic mechanisms in the nervous system infection and the neurological involvement is essential to assess possible long-term neurological alteration of COVID-19. Here, we provide an overview of associated literature regarding possible routes of COVID-19 neuroinvasion, such as the trans-synapse-connected route in the olfactory pathway and peripheral nerve terminals and its neurological implications in the central nervous system.

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BACKGROUND: Neurological disorders in kidney transplant patients may be related to several factors, including high toxicity to the use of immunosuppressive drugs. OBJECTIVE: To find out whether there was association between neurological complications and immunosuppression in a sample of patients who received renal transplantation. METHODS: Cross-sectional study in which 121 renal transplant patients participated, of which 22 (18%) had neurological disorders, chi-squared test was used to analyze the relation between neurological disorders and comorbidity such as diabetes mellitus and hypertension and time of immunosuppressant use. A significance level of p <0.05 was accepted for all determinations. RESULTS: Of the subjects studied, 13 were male (59%) and nine female (41%). The mean age of the patients included in the study was 33 ± 12 years. 59% of neurological disorders occurred between six months and five years after patients had received the transplant. Neurological alterations found were: tremor (7.4%), dizziness (4.1%), peripheral neuropathy (3.3%), headache (2.4%), and decreased strength (0.8%). CONCLUSION: No statistically significant association was found between neurological disorders and immunosuppressant use, or between them and the duration of immunosuppression.

Antecedentes: Las alteraciones neurológicas en pacientes trasplantados de riñón pueden relacionarse con diversos factores, entre ellos la toxicidad secundaria al uso de medicamentos inmunosupresores. Objetivo: Conocer si existió asociación entre complicaciones neurológicas e inmunosupresión en una muestra de pacientes que recibieron trasplante renal. Métodos: Estudio transversal en el que participaron 121 pacientes con trasplante renal, de los cuales 22 (18 %) presentaron alteraciones neurológicas, Se usó χ2 para analizar la relación entre alteraciones neurológicas y comorbilidad como diabetes mellitus e hipertensión arterial y tiempo del uso de inmunosupresor. Se aceptó un nivel de significación p<0.05 para todas las determinaciones Resultados: De los sujetos estudiados, 13 eran hombres (59%) y nueve mujeres (41%). La edad media de los pacientes incluidos en el estudio fue 33 ± 12 años. El 59 % de las alteraciones neurológicas ocurrieron entre seis meses y cinco años de que los pacientes habían recibido el trasplante. Las alteraciones neurológicas encontradas fueron: temblor (7.4%), vértigo (4.1%), neuropatía periférica (3.3%), cefalea (2.4%) y disminución de la fuerza (0.8 %). Conclusión: No se encontró relación estadísticamente significativa entre las alteraciones neurológicas y el inmunosupresor usado ni entre éstas y el tiempo que duró la inmunosupresión.

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Leishmaniasis is a vectorborne disease caused by Leishmania protozoa, which is a major health problem and a neglected disease common in many regions of the world. Leishmania is an intracellular parasite transmitted by sand flies that causes clinical manifestations ranging from a severe and potentially fatal disease named visceral leishmaniasis to less severe but in many cases disfiguring diseases that mainly affect the skin or mucosal tissues, known as cutaneous leishmaniasis. Despite the detection of Leishmania parasites in the brain and cerebrospinal fluid of human patients and dogs, epidemiological data, as well as information about the mechanisms of central and peripheral nervous system alterations, are poorly described. This review is focused on the current knowledge about the neurological manifestations and immunopathogenic mechanisms in human patients and animals infected with Leishmania.

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Clinic-pathological aspects and the pathogenesis of experimental abamectin poisoning were studied, after subcutaneous administration of different abamectin doses in 9 calves, as well as the clini-cal and pathological aspects of 74 cases of the iatrogenic poisoning with this drug in cattle, which occurred in the states of Rio Grande do Sul, Pará, Maranhão, Paraíba and Mato Grosso do Sul. From the 9 calves submitted to experimental administration of single doses, 5 calves died (4 calves received doses 6-10 times higher than recommended, and one received the therapeutic daily dose during 11 days). Abamectin poisoning induces neurological dysfunctions, characterized by an initial phase of hyperexcitability, followed by widespread muscular hypotony and progressive depression. No macroscopic or microscopic alterations were observed in the central nervous system or in any other organ. It is concluded that abamectin is an antihelmintic which should be used with restriction, because of the risks leading to death when used in young calves, even in therapeutic doses.

Estudaram-se os aspectos clínico-patológicos e patogenéticos verificados após a administração experimental subcutânea de diferentes doses de abamectina em nove bezerros. Também são apresentados os dados clínico-patológicos sobre a ocorrência de intoxicação iatrogênica por essa droga que resultaram em 74 mortes em bovinos nos Estados do Rio Grande do Sul, Pará, Maranhão, Paraíba e Mato Grosso do Sul. No presente estudo, dos nove bezerros submetidos à administração experimental, cinco morreram (quatro que receberam doses únicas de 6-10 vezes superior à recomendada e um que recebeu diariamente a dose terapêutica durante 11 dias). A intoxicação por abamectina induz a disfunções neurológicas, caracterizadas por uma fase inicial de hiperexcitabilidade, seguida por hipotonia muscular generalizada e depressão progressiva. Nenhuma alteração macroscópica ou microscópica foi observada no sistema nervoso central ou em qualquer outro órgão. Conclui-se que a abamectina é um medicamento que deve ser utilizado com restrições, pois há riscos de morte quando utilizado em bezerros jovens, até mesmo na dose terapêutica.