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BACKGROUND: Recent literature highlights anomalous cranial nerves in the sinonasal region, notably in the sphenoid and maxillary sinuses, linked to anatomical factors. However, data on the suspended infraorbital canal (IOC) variant is scarce in cross-sectional imaging. Anatomical variations in the sphenoid sinuses, including optic, maxillary, and vidian nerves, raise interest among specialists involved in advanced sinonasal procedures. The infraorbital nerve's (ION) course along the orbital floor and its abnormal positioning within the orbital and maxillary sinus region pose risks of iatrogenic complications. A comprehensive radiological assessment is crucial before sinonasal surgeries. Cone-beam computed tomography (CBCT) is preferred for its spatial resolution and reduced radiation exposure. OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants of the infraorbital canal (IOC) and report its association with clinical condition or surgical implication. METHODS: We searched Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to June 2023. Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Preliminary results show that three types are prevalent, type 1: the IOC does not bulge into the maxillary sinus (MS); therefore, the infraorbital foramen through the anterior wall of MS could be used for identification of the ION. Type 2: the IOC divided the orbital floor into medial and lateral aspects. Type 3: the IOC hangs in the MS and the entire orbital floor lying above the IOC. From which the clinical implications where mainly surgical, in type 1 the infraorbital foramen through the anterior wall of MS could be used for identification of the ION, while in type 2, since the lateral orbital floor could not be directly accessed an inferiorly transposition of ION is helpful to expose the lateral orbital wall directly with a 0 scope; or using angled endoscopes and instruments, however, the authors opinion is that direct exposure potentially facilitates the visualization and management in complex situations such as residual or recurrent mass, foreign body, and fracture located at the lateral aspect of the canal. Lastly, in type 3, the ION it's easily exposed with a 0° scope. CONCLUSIONS: This systematic review identified four IOC variants: Type 1, within or below the MS roof; Type 2, partially protruding into the sinus; Type 3, fully protruding into the sinus or suspended from the roof; and Type 4, in the orbital floor. Clinical recommendations aim to prevent nerve injuries and enhance preoperative assessments. However, the lack of consistent statistical methods limits robust associations between IOC variants and clinical outcomes. Data heterogeneity and the absence of standardized reporting impede meta-analysis. Future research should prioritize detailed reporting, objective measurements, and statistical approaches for a comprehensive understanding of IOC variants and their clinical implications. Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/UGYFZ .
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Variação Anatômica , Tomografia Computadorizada de Feixe Cônico , Órbita , Humanos , Nervos Cranianos/anatomia & histologia , Nervos Cranianos/diagnóstico por imagem , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/anatomia & histologia , Seio Maxilar/cirurgia , Órbita/anatomia & histologia , Órbita/diagnóstico por imagem , Seio Esfenoidal/anatomia & histologia , Seio Esfenoidal/diagnóstico por imagemRESUMO
Background: Trigeminal neuralgia (TN) is a highly disabling facial pain syndrome, historically known as the suicide disease, in which most cases can be cured with appropriate surgical treatment. Case Description: We present the case of a 43-year-old male farmer with acute, self-limiting episodes of shock-like pain on the left side of the face that started in June of 2021. He was diagnosed with TN and was treated with carbamazepine. Magnetic resonance imaging was performed, which revealed an epidermoid cyst (EC) at the prepontine cistern with an extension to the left cerebellopontine angle. The neurosurgery department at our institution was consulted, which performed surgical tumor resection and Vth cranial nerve decompression. During the resection, a neurovascular conflict (NVC) was identified at the root entry zone. After the resection around the nerve and its whole tract was completed, a microvascular decompression (MVD) was performed. Conclusion: TN secondary to EC in association with a NVC is a rare phenomenon, due to the growth pattern of the EC. TN may remit if an appropriate treatment is carried out. In cases of NVC, an MVD is required apart from an appropriate resection to achieve pain relief.
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The neurovascular unit, composed of vascular endothelium, vascular smooth muscle, extracellular matrix components, pericytes, astrocytes, microglia, and neurons, allows the highly regulated exchange of molecules and the limited trafficking of cells to the brain through coordinated signaling activity. The passage of peripheral immune cells to the brain parenchyma is observed when there is clear damage to the barriers of this neurovascular unit, as occurs in traumatic brain injury. The possibility of leukocyte infiltration to the brain in neurodegenerative conditions has been proposed. In this review, we focus on describing the evidence for peripheral immune cell infiltration to the brain in the two most frequent neurodegenerative diseases: Alzheimer's and Parkinson's diseases. In particular, we address the mechanisms that promote the passage of these cells into the brain under such pathological conditions. We also discuss the relevance of the resulting cellular interactions, which provide evidence that the presence of peripheral immune cells in the brain is a key point in these neurodegenerative diseases.
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Doença de Alzheimer , Encéfalo , Doença de Parkinson , Humanos , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Doença de Parkinson/imunologia , Doença de Parkinson/patologia , Animais , Encéfalo/imunologia , Encéfalo/patologia , Leucócitos/imunologia , Leucócitos/patologia , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologiaRESUMO
Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in the brain parenchyma and within the walls of cerebral vessels. The hippocampus-a complex brain structure with a pivotal role in learning and memory-is implicated in this disease. However, there is limited data on vascular changes during AD pathological degeneration in this susceptible structure, which has distinctive vascular traits. Our aim was to evaluate vascular alterations in the hippocampus of AD patients and PDAPP-J20 mice-a model of AD-and to determine the impact of Aß40 and Aß42 on endothelial cell activation. We found a loss of physical astrocyte-endothelium interaction in the hippocampus of individuals with AD as compared to non-AD donors, along with reduced vascular density. Astrocyte-endothelial interactions and levels of the tight junction protein occludin were altered early in PDAPP-J20 mice, preceding any signs of morphological changes or disruption of the blood-brain barrier in these mice. At later stages, PDAPP-J20 mice exhibited decreased vascular density in the hippocampus and leakage of fluorescent tracers, indicating dysfunction of the vasculature and the BBB. In vitro studies showed that soluble Aß40 exposure in human brain microvascular endothelial cells (HBMEC) was sufficient to induce NFκB translocation to the nucleus, which may be linked with an observed reduction in occludin levels. The inhibition of the membrane receptor for advanced glycation end products (RAGE) prevented these changes in HBMEC. Additional results suggest that Aß42 indirectly affects the endothelium by inducing astrocytic factors. Furthermore, our results from human and mouse brain samples provide evidence for the crucial involvement of the hippocampal vasculature in Alzheimer's disease.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Astrócitos , Hipocampo , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Humanos , Hipocampo/patologia , Hipocampo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Masculino , Idoso , Camundongos Transgênicos , Feminino , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Idoso de 80 Anos ou mais , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/metabolismo , Camundongos , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
PURPOSE: Diagnostic cerebral digital subtraction angiography (DSA) is an invasive examination that involves catheterization of the major supra-aortic arterial trunks and evaluation of intracranial vessels for diagnostic purposes. Although considered the gold standard method for investigating cerebrovascular diseases, DSA carries measurable and potentially serious complication rates. This report describes the frequency of neurological and non-neurological complications of DSA performed in five hospitals in the state of São Paulo, Brazil, and analyzes them in different disease subgroups. It has a special focus on thromboembolic cerebral complications. METHODS: We retrospectively reviewed clinical records of all adult patients who underwent DSAs between January 2019 and December 2022. Demographic variables, DSA reports, CT/MRI reports, and clinical follow-up notes were reviewed. RESULTS: Twenty-four patients experienced some type of complication among 2,457 diagnostic DSAs (0.97%). Thromboembolic complications were recorded in 9 patients (0.36%), and access site hematomas larger than 5 cm were registered in six patients (0.24%). There was a statistical trend for thromboembolic complications in patients with cervical and/or intracranial atherosclerosis (p = 0.07), but age was not associated with them (p = 0.93). Patients who received heparin had lower rates of embolic complications than those who did not receive it, but there was no statistically significant difference (p = 0.17). Intravenous administration of heparin showed a trend toward significance with groin hematoma (p = 0.10). CONCLUSION: Diagnostic catheter DSAs have low complication rates.
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Angiografia Digital , Angiografia Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Fatores de Risco , Angiografia Cerebral/efeitos adversos , Adulto , Tromboembolia/diagnóstico por imagem , Tromboembolia/epidemiologia , Brasil/epidemiologiaRESUMO
BACKGROUND: Neurosurgical training continuously seeks innovative methods to enhance the acquisition of essential technical skills for neurosurgeons worldwide. While various training models have been employed, few truly replicate real-life conditions optimally. Human placenta is a good model for neurosurgical microsurgery training due to its anatomic similarities to neurovascular structures. Placental vessels exhibit a branching pattern and caliber comparable with intracranial vessels, making them suitable for practicing microsurgical techniques. The study aims to delineate the anatomic zones of the placenta and propose a segmented training model, resulting in a reproducible, cost-effective, and realistic neurosurgical microsurgery training environment. METHODS: Twenty human placentas were meticulously prepared, injected with dyes, and categorized into zones on the basis of anatomic features. Measurements of placental vessels were recorded and compared with cerebral vessels. The placenta was divided into 4 quadrants to facilitate specific training techniques. RESULTS: Our results revealed varying vessel diameters across placental zones, closely resembling cerebral vessels. Different microsurgical techniques were applied to specific placental zones, thereby optimizing training scenarios. The applicability section described exercises such as membrane dissection, vessel skeletonization, aneurysm creation, vascular bypass, and tumor dissection within the placental model, providing detailed guidance on the zones suitable for each exercise. CONCLUSIONS: Human placenta serves as an effective microsurgical training model for neurosurgery, enhancing neurosurgeons' skills through anatomic segmentation. Integrating this model into training programs can significantly contribute to skill acquisition and improved surgical outcomes. Further research is warranted to refine and expand its utilization, complemented by clinical experiences and other simulation tools.
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Neurocirurgia , Placenta , Humanos , Gravidez , Feminino , Placenta/irrigação sanguínea , Modelos Anatômicos , Microcirurgia/métodos , Neurocirurgia/educação , Procedimentos Neurocirúrgicos/métodos , Competência ClínicaRESUMO
Abstract Background Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. Objective To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. Methods This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. Results A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. Conclusion This exploratory analysis suggests that COVID-19 does not impair ICC.
Resumo Antecedentes Pacientes com doença grave por coronavírus-19 (COVID-19) podem necessitar do uso de ventilação mecânica (VM) invasiva por um período prolongado. Parâmetros agressivos de VM têm sido associados a alterações na pressão intracraniana (PIC) em pacientes com doenças intracranianas agudas. Elevações significativas da PIC podem comprometer a complacência intracraniana (CIC) e a hemodinâmica cerebrovascular (HVC). No entanto, os efeitos desses parâmetros em indivíduos sem doenças neurológicas ainda não foram sistematicamente avaliados. Objetivo Avaliar a CIC em pacientes em VM com COVID-19 comparados com outros diagnósticos, para melhor caracterizar os efeitos da VM e COVID-19 sobre a CIC. Também foi feita a comparação entre a CIC em pacientes com COVID-19 sem VM e voluntários saudáveis, para avaliar o efeito isolado da COVID-19 sobre a ICC. Métodos Trata-se de um estudo exploratório, observacional com amostra por conveniência. A CIC foi avaliada com um dispositivo não invasivo de monitoramento da PIC. A relação P2/P1 foi calculada dividindo-se a amplitude desses dois pontos, sendo definida como "anormal" quando P2 > P1. A análise estatística foi realizada usando um modelo linear misto com efeitos aleatórios para comparar a relação P2/P1 nos quatro grupos no primeiro dia de monitoramento. Resultados Uma amostra de conveniência com 78 voluntários (15 COVID-19 em VM, 15 sem COVID-19 em VM, 24 com COVID em respiração espontânea e 24 saudáveis) foram prospectivamente incluídos. Não houve diferença nas razões P2/P1 entre pacientes em VM com e sem COVID-19, nem entre pacientes sem VM com COVID-19 ou saudáveis. No entanto, a relação P2/P1 foi maior em pacientes com COVID-19 com uso de VM do que naqueles sem. Conclusão Os dados dessa análise exploratória sugerem que a COVID-19 não prejudica a CIC.
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BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a specific subtype of diabetes with an uncertain impact on mortality and morbidity in post-transplant patients. Diabetic retinopathy is the most common microvascular complication of diabetes mellitus, but the long-term clinical progression in PTDM is unknown. New technologies are being used to assess pre-clinical signs of retinal changes, such as swept-source optical coherence tomography (OCT) and OCT-angiography. The aim of this study was to detect pre-clinical structural and vascular changes in the retina using swept-source-OCT and OCT-angiography in patients with PTDM. METHODS: In this retrospective cohort study, post-kidney transplant patients were divided into PTDM and non-PTDM (control) groups. Both eyes of eligible PTDM patients and controls were included in this study. Inner retinal layer thickness was measured with swept-source-OCT. Retinal capillary density and the foveal avascular zone were measured with OCT-angiography. RESULTS: In the PTDM group, reduced thickness was found in the inferior ganglion cell layer plus inner plexiform layer (95% CI -8.76 to -0.68; p = 0.022) and the temporal inferior segment (95% CI -10.23 to -0.76; p = 0.024) of the inner retina, as well as in the retinal nerve fiber layer in the temporal (95% CI -34.78 to -9.28 p = 0.001) and temporal inferior segments (95% CI -33.26 to -5.03 p = 0.008). No significant differences were found in the vascular capillary plexus between groups at all depths, segments, or foveal avascular zone (p = 0.088). CONCLUSIONS: According to OCT-angiography, PTDM patients had reduced inner neurosensory retinal layers but no significant change in vascular density, which suggests that early neuroretinal degeneration might occur prior to vascular changes secondary to PTDM. Prospective studies could help elucidate the clinical course of retinal neuropathy and microvascular pathology in PTDM and provide a better understanding of PTDM complications.
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PURPOSE: To evaluate the proximity of the ulnar neurovascular structures to the endoscopic blade during endoscopic carpal tunnel release (CTR). METHODS: Ten fresh-frozen cadaver hands were used to perform endoscopic CTR using devices from two manufacturers. The skin was excised from the palm, and the endoscopic carpal tunnel blade was deployed at the distal edge of the transverse carpal ligament (TCL). The blade's proximity to the ulnar neurovascular bundle, deep ulnar motor branch, superficial palmar arch, and median nerve was recorded. Following release of the TCL, the device was turned ulnar to the maximal extent to determine if direct injury to the ulnar neurovascular bundle was possible. RESULTS: The average longitudinal distance from the end of the TCL to the superficial palmar arch was 13.3 mm (range, 8.4-20.9) and to the ulnar motor branch was 10.8 mm (range, 4.0-15.0). The average transverse distance from the end of the TCL to the ulnar neurovascular bundle was 5.9 mm (range, 3.1-7.8) and to the median nerve was 3.3 mm (range, 0-6.5). In two of our specimens, the median nerve subluxated volarly over the cutting device. When placing the blade at the distal edge of the TCL, injury to the deep motor branch of the ulnar nerve, ulnar neurovascular bundle, or superficial palmar arch was not possible in any specimens using the tested devices, even when turning the blade directly toward these structures. CONCLUSIONS: There is a low likelihood of direct injury to the ulnar neurovascular bundle during endoscopic CTR. CLINICAL RELEVANCE: These results suggest that injury to the ulnar neurovascular bundle is unlikely during endoscopic CTR if the distal aspect of the transverse carpal ligament can be clearly identified prior to release. Control of the median nerve is also important to prevent subluxation over the cutting device.
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Introducción: Los síndromes de compresión de la salida torácica, en ocasiones poco definidos, se caracterizan por cervicobraquialgia como principal síntoma. Se deben a una compresión del tronco inferior del plexo braquial o de los vasos subclavios, estructuras que atraviesan la salida torácica. No ha sido establecida ninguna técnica diagnóstica y su tratamiento incluye la fisioterapia, medicamentos como los analgésicos y, en algunos casos, la cirugía. Objetivo: Presentar los resultados obtenidos con el tratamiento quirúrgico a pacientes que fueron diagnosticados, según su etiología, con diferentes síndromes de la salida torácica. Métodos: Se realizó un estudio a 131 pacientes diagnosticados como síndromes de la salida torácica, atendidos con síntomas referentes a estos en un periodo de 12 años, y que fueron intervenidos quirúrgicamente. El diagnóstico causal se basó en la clínica, estudios radiológicos, ultrasonográficos y electromiográficos y valoración de los factores de riesgo. Resultados: La edad más frecuente fue la tercera década de la vida y el sexo femenino fue más afectado. Como agente causal, las costillas cervicales supernumerarias y las apófisis costiformes se presentaron en mayor porcentaje, contituyendo la escalenotomia anterior y media el proceder quirúrgico más efectuado. Conclusiones: Los síntomas neurológicos evidenciaron una compresión nerviosa en la mayoría de los casos, y los resultados evaluados como buenos los más frecuentes, demostrando que el tratamiento quirúrgico de esta patología forma parte esencial de las mismas(AU)
Introduction: Thoracic outlet compression syndromes, sometimes poorly defined, are characterized by cervicobrachialgia as the main symptom. They are due to compression of the lower trunk of the brachial plexus or the subclavian vessels, structures that cross the thoracic outlet. No diagnostic technique has been established and its treatment includes physiotherapy, medications such as analgesics and, in some cases, surgery. Objective: To present the results obtained with the surgical treatment of patients who were diagnosed, according to their etiology, with different thoracic outlet syndromes. Methods: A study was carried out on 131 patients diagnosed as thoracic outlet syndromes, treated with symptoms related to these in a period of 12 years, and who underwent surgery. The causal diagnosis was based on the symptoms, radiological, ultrasonographic and electromyographic studies and assessment of risk factors. Results: The most frequent age was the third decade of life and the female sex was more affected. As a causal agent, the supernumerary cervical ribs and the costiform processes were present in a higher percentage, constituting the anterior and median scalenotomy the most performed surgical procedure. Conclusions: The neurological symptoms evidenced nerve compression in most cases, and the results evaluated as good in the most frequent, demonstrating that the surgical treatment of this pathology is an essential part of them(AU)
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HumanosRESUMO
BACKGROUND: Induced pluripotent stem cells (iPSCs) show great ability to differentiate into any tissue, making them attractive candidates for pathophysiological investigations. The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments, both structural and functionally. The literature still lacks consensus on the best conditions to mimic the blood-brain barrier (BBB) for drug screening and other personalized therapies. The development of models based on BBB-on-a-chip using iPSCs is promising and is a potential alternative to the use of animals in research. AIM: To analyze the literature for BBB models on-a-chip involving iPSCs, describe the microdevices, the BBB in vitro construction, and applications. METHODS: We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices. Thirty articles were identified, wherein only 14 articles were finally selected according to the inclusion and exclusion criteria. Data compiled from the selected articles were organized into four topics: (1) Microfluidic devices design and fabrication; (2) characteristics of the iPSCs used in the BBB model and their differentiation conditions; (3) BBB-on-a-chip reconstruction process; and (4) applications of BBB microfluidic three-dimensional models using iPSCs. RESULTS: This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research. Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups. Conventional polydimethylsiloxane was the most used material to fabricate in-house chips (57%), whereas few studies (14.3%) adopted polymethylmethacrylate. Half the models were constructed using a porous membrane made of diverse materials to separate the channels. iPSC sources were divergent among the studies, but the main line used was IMR90-C4 from human fetal lung fibroblast (41.2%). The cells were differentiated through diverse and complex processes either to endothelial or neural cells, wherein only one study promoted differentiation inside the chip. The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen IV (39.3%), followed by cell seeding in single cultures (36%) or co-cultures (64%) under controlled conditions, aimed at developing an in vitro BBB that mimics the human BBB for future applications. CONCLUSION: This review evidenced technological advances in the construction of BBB models using iPSCs. Nonetheless, a definitive BBB-on-a-chip has not yet been achieved, hindering the applicability of the models.
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Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Camundongos , Animais , Doença de Alzheimer/metabolismo , Placa Amiloide/metabolismo , Células Endoteliais/metabolismo , Camundongos Transgênicos , Angiopatia Amiloide Cerebral/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Peptídeos beta-Amiloides/metabolismoRESUMO
Neonatal encephalopathy (NE) is a pathological condition that describes a neurocognitive malfunction in the newborn that arises from fetal, peripartum, or intrapartum events of multifactorial nature, having a poor prognosis and accounting for an incidence of 5-8 per 1000 live births. Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most studied paradigms of NE, caused by a scarce cerebral perfusion and oxygen supply during perinatal life. The cerebral hypoxic-ischemic insult promotes a loss of permeability of the blood-brain barrier (BBB), an essential structural intermediary of blood-brain communication. This permeability disruption is associated with an increase in inflammatory cytokines, an increase of adhesion molecules, and oxidative stress which disturb the tight junction (TJ) performance and enable transcytosis and paracellular leakage, ultimately leading to death from brain cells. In this context, TJs proteins are essential to preserving the barrier mechanical stability and signaling that modulates the brain-blood vessel multicellular domains, known as neurovascular units (NVU). Recent studies have proposed different strategies with neuroprotective effects that allow for maintaining or restoring the integrity and permeability of the BBB. This review identifies and discusses regulator mechanisms and novel aspects of TJs in the BBB disruption induced by cerebral hypoxic insults during the perinatal period, evaluating potential pharmacological strategies to safeguard BBB integrity.
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Barreira Hematoencefálica , Hipóxia-Isquemia Encefálica , Recém-Nascido , Gravidez , Feminino , Humanos , Barreira Hematoencefálica/metabolismo , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Junções Íntimas/metabolismo , Encéfalo/metabolismo , Hipóxia/metabolismo , PermeabilidadeRESUMO
The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load.
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Vírus da Encefalite Equina Venezuelana , Encefalomielite Equina Venezuelana , Humanos , Animais , Cavalos , Vírus da Encefalite Equina Venezuelana/fisiologia , Barreira Hematoencefálica , Encefalomielite Equina Venezuelana/tratamento farmacológico , Encefalomielite Equina Venezuelana/prevenção & controle , Células Endoteliais , Sistemas MicrofisiológicosRESUMO
The neurovascular unit (NVU) is a multicellular structure comprising of neurons, glial cells, and non-neural cells, and it is supported by a specialized extracellular matrix, the basal lamina. Astrocytes, brain microvascular endothelial cells (BMECs), pericytes, and smooth muscle cells constitute the blood-brain barrier (BBB). BMECs have a mesodermal origin and invade the nervous system early in neural tube development, forming the BBB anatomical core. BMECs are connected by adherent junction complexes composed of integral membrane and cytoplasmic proteins. In vivo and in vitro studies have shown that, given the proximity and relationship with neural cells, BMECs acquire a unique gene expression profile, proteome, and specific mechanical and physical properties compared to endothelial cells from the general vasculature. BMECs are fundamental in maintaining brain homeostasis by regulating transcellular and paracellular transport of fluids, molecules, and cells. Therefore, it is essential to gain in-depth knowledge of the dynamic cellular structure of the cells in the NVU and their interactions with health and disease. Here we describe a significantly improved and simplified protocol using C57BL/6 newborn mice at postnatal day 1 (PND1) to isolate, purify, and culture BMECs monolayers in two different substrates (glass coverslips and transwell culture inserts). In vitro characterization and validation of the BMEC primary culture monolayers seeded on glass or insert included light microscopy, immunolabeling, and gene expression profile. Transendothelial electrical resistance (TEER) measurement and diffusion test were used as functional assays for adherent junction complexes and integrity and permeability of BMECs monolayers. The protocol presented here for the isolation and culture of BMECs is more straightforward than previously published protocols and yields a high number of purified cells. Finally, we tested BMECs function using the oxygen-glucose deprivation (OGD) model of hypoxia. This protocol may be suitable as a bioscaffold for secondary cell seeding allowing the study and better understanding of the NVU.
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BACKGROUND: Transverse myelitis (TM) is characterized by acute development of motor, sensory and autonomic dysfunctions due to horizontally diffused inflammation in one or more segments of the spinal cord in the absence of a compressive lesion. The not well-known inflammation process induces demyelination resulting in neurological dysfunction. CASE PRESENTATION: In this case report we used a functional Near-Infrared Spectroscopy (fNIRS) technique to evaluate changes in the peri-spinal vascular response induced by a peripheral median nerve electrical stimulation in a patient with chronic transverse myelitis (TM). fNIRS showed drastically reduced signal amplitude in the peri-spinal vascular response, compared to that obtained from a healthy control group throughout most of the C7-T1 and T10-L2 spinal cord segments. CONCLUSION: The potential use of this relatively non-invasive fNIRS technology support the potential clinical application of this method for functional test of the spinal cord through the assessment of the spinal neurovascular response.
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Doenças do Sistema Nervoso Autônomo , Mielite Transversa , Humanos , Mielite Transversa/etiologia , Espectroscopia de Luz Próxima ao Infravermelho , Medula Espinal/patologia , Doenças do Sistema Nervoso Autônomo/patologia , Inflamação/complicaçõesRESUMO
Schizophrenia is a chronic debilitating mental disorder characterized by perturbations in thinking, perception, and behavior, along with brain connectivity deficiencies, neurotransmitter dysfunctions, and loss of gray brain matter. To date, schizophrenia has no cure and pharmacological treatments are only partially efficacious, with about 30% of patients describing little to no improvement after treatment. As in most neurological disorders, the main descriptions of schizophrenia physiopathology have been focused on neural network deficiencies. However, to sustain proper neural activity in the brain, another, no less important network is operating: the vast, complex and fascinating vascular network. Increasing research has characterized schizophrenia as a systemic disease where vascular involvement is important. Several neuro-angiogenic pathway disturbances have been related to schizophrenia. Alterations, ranging from genetic polymorphisms, mRNA, and protein alterations to microRNA and abnormal metabolite processing, have been evaluated in plasma, post-mortem brain, animal models, and patient-derived induced pluripotent stem cell (hiPSC) models. During embryonic brain development, the coordinated formation of blood vessels parallels neuro/gliogenesis and results in the structuration of the neurovascular niche, which brings together physical and molecular signals from both systems conforming to the Blood-Brain barrier. In this review, we offer an upfront perspective on distinctive angiogenic and neurogenic signaling pathways that might be involved in the biological causality of schizophrenia. We analyze the role of pivotal angiogenic-related pathways such as Vascular Endothelial Growth Factor and HIF signaling related to hypoxia and oxidative stress events; classic developmental pathways such as the NOTCH pathway, metabolic pathways such as the mTOR/AKT cascade; emerging neuroinflammation, and neurodegenerative processes such as UPR, and also discuss non-canonic angiogenic/axonal guidance factor signaling. Considering that all of the mentioned above pathways converge at the Blood-Brain barrier, reported neurovascular alterations could have deleterious repercussions on overall brain functioning in schizophrenia.
RESUMO
Introducción: El síndrome de la salida torácica abarca diversos trastornos, que se producen como consecuencia de la compresión intermitente o persistente de los distintos elementos que salen del tórax hacia el brazo y ocasionan síntomas vasculares, neurológicos o combinados, los cuales frecuentemente tienen una indicación quirúrgica para su resolución. Objetivo: Evaluar los resultados de diez años de experiencia del tratamiento quirúrgico del síndrome de la salida torácica en los pacientes intervenidos en el Hospital General Docente "Dr. Agostinho Neto", de Guantánamo. Métodos: Se realizó un estudio retrospectivo de corte transversal en pacientes diagnosticados en el servicio de Angiología y Cirugía Vascular del Hospital General Docente "Dr. Agostinho Neto", de Guantánamo, con el síndrome de la salida torácica, los cuales se sometieron a tratamiento quirúrgico en el período 2009-2019. Se evaluaron las siguientes variables: edad, sexo, síndromes diagnosticados, técnicas quirúrgicas, complicaciones, y sintomatología antes y después de la cirugía. Resultados: Predominó el sexo femenino, fundamentalmente entre 40 y 50 años. El dolor fue el síntoma predominante y el síndrome más diagnosticado resultó el costo-clavicular. Se destacó como la técnica quirúrgica más empleada la desinserción del escaleno anterior, seguida por la resección de la primera costilla. La lesión pleural y neural aparecieron como las complicaciones más frecuentes. Se constató la mejoría clínica de los pacientes luego de la intervención quirúrgica en la mayoría de los casos. Conclusiones: Se demostró que el tratamiento quirúrgico del síndrome de la salida torácica puede ser una alternativa efectiva para los pacientes aquejados por esta entidad(AU)
Introduction: Thoracic outlet syndrome covers various disorders, which occur as a result of intermittent or persistent compression of the different elements that leave the chest to the arm and cause vascular, neurological or combined symptoms, which often have a surgical indication for their resolution. Objective: Assess the results of ten years of experience in the surgical treatment of thoracic outlet syndrome in patients operated on at "Dr. Agostinho Neto" General Teaching Hospital in Guantánamo. Methods: A retrospective cross-sectional study was conducted in patients diagnosed with thoracic outlet syndrome in the Angiology and Vascular Surgery Service of "Dr. Agostinho Neto" General Teaching Hospital, Guantánamo , who underwent surgical treatment in the period 2009-2019. The following variables were evaluated: age, sex, diagnosed syndromes, surgical techniques, complications, and symptoms before and after surgery. Results: The female sex predominated, mainly in the ages from 40 to 50. Pain was the predominant symptom, and the costo-clavicular syndrome turned out to be the most diagnosed one. The most used surgical technique was the disinsertion of the anterior scalene, followed by the resection of the first rib. Pleural and neural injury appeared as the most frequent complications. The clinical improvement of patients after surgical intervention was found in most cases. Conclusions: It was demonstrated that surgical treatment of thoracic outlet syndrome can be an effective alternative for patients suffering from this entity(AU)
Assuntos
Humanos , Feminino , Adulto , Síndrome do Desfiladeiro Torácico/cirurgia , Procedimentos Cirúrgicos Vasculares , Dor , Procedimentos Cirúrgicos Operatórios , Estudos TransversaisRESUMO
Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.