Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain. Tissue samples from 24 deceased COVID-19-positive individuals were analyzed. Reverse transcription real-time PCR (RT-qPCR) was performed on selected brain regions, including the choroid plexus, to detect SARS-CoV-2 viral RNA. Additionally, immunofluorescence staining and confocal microscopy were used to detect and localize two characteristic proteins of SARS-CoV-2: the spike protein S1 and the nucleocapsid protein. RT-qPCR analysis confirmed the presence of SARS-CoV-2 viral RNA in the choroid plexus. Immunohistochemical staining revealed viral particles localized in the epithelial cells of the choroid plexus, with the spike protein S1 detected in the late endosomes. Our findings suggest that the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus serves as a route of entry for SARS-CoV-2 into the CNS. This study contributes to the understanding of the mechanisms underlying CNS involvement in COVID-19 and highlights the importance of further research to explore potential therapeutic strategies targeting this entry pathway.
- MeSH
- COVID-19 * virologie MeSH
- dospělí MeSH
- fosfoproteiny * metabolismus MeSH
- glykoprotein S, koronavirus * genetika metabolismus MeSH
- hematoencefalická bariéra * virologie MeSH
- internalizace viru MeSH
- koronavirové nukleokapsidové proteiny MeSH
- lidé středního věku MeSH
- lidé MeSH
- plexus chorioideus * virologie MeSH
- RNA virová * genetika MeSH
- SARS-CoV-2 * fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The choroid plexus is located in the cerebral ventricles. It consists of a stromal core and a single layer of cuboidal epithelial cells that forms the blood-cerebrospinal barrier. The main function of the choroid plexus is to produce cerebrospinal fluid. Subarachnoid hemorrhage due to aneurysm rupture is a devastating type of hemorrhagic stroke. Following subarachnoid hemorrhage, blood and the blood degradation products that disperse into the cerebrospinal fluid come in direct contact with choroid plexus epithelial cells. The aim of the current study was to elucidate the pathophysiological cascades responsible for the inflammatory reaction that is seen in the choroid plexus following subarachnoid hemorrhage. METHODS: Subarachnoid hemorrhage was induced in rats by injecting non-heparinized autologous blood to the cisterna magna. Increased intracranial pressure following subarachnoid hemorrhage was modeled by using artificial cerebrospinal fluid instead of blood. Subarachnoid hemorrhage and artificial cerebrospinal fluid animals were left to survive for 1, 3, 7 and 14 days. Immunohistochemical staining of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β, CCR2 and CX3CR1 was performed on the cryostat sections of choroid plexus tissue. The level of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β was detected by measuring immunofluorescence intensity in randomly selected epithelial cells. The number of CCR2 and CX3CR1 positive cells per choroid plexus area was manually counted. Immunohistochemical changes were confirmed by Western blot analyses. RESULTS: Immunohistochemical methods and Western blot showed increased levels of TLR9 and a slight increase in TLR4 and FRP2 following both subarachnoid hemorrhage as well as the application of artificial cerebrospinal fluid over time, although the individual periods were different. The levels of TNFα and IL-1β increased, while CCL2 level decreased slightly. Accumulation of macrophages positive for CCR2 and CX3CR1 was found in all periods after subarachnoid hemorrhage as well as after the application of artificial cerebrospinal fluid. DISCUSSION: Our results suggest that the inflammation develops in the choroid plexus and blood-cerebrospinal fluid barrier in response to blood components as well as acutely increased intracranial pressure following subarachnoid hemorrhage. These pro-inflammatory changes include accumulation in the choroid plexus of pro-inflammatory cytokines, innate immune receptors, and monocyte-derived macrophages.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.
- MeSH
- analgetika terapeutické užití aplikace a dávkování MeSH
- antiflogistika nesteroidní * terapeutické užití aplikace a dávkování MeSH
- dospělí MeSH
- hydrocefalus etiologie MeSH
- ischemie mozku farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metamizol * terapeutické užití aplikace a dávkování MeSH
- retrospektivní studie MeSH
- senioři MeSH
- subarachnoidální krvácení * farmakoterapie komplikace MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Diffusion-weighted imaging (DWI) and its numerical expression via apparent diffusion coefficient (ADC) values are commonly utilized in non-invasive assessment of various brain pathologies. Although numerous studies have confirmed that ADC values could be pathognomic for various ring-enhancing lesions (RELs), their true potential is yet to be exploited in full. The article was designed to introduce an image analysis method allowing REL recognition independently of either absolute ADC values or specifically defined regions of interest within the evaluated image. For this purpose, the line of interest (LOI) was marked on each ADC map to cross all of the RELs' compartments. Using a machine learning approach, we analyzed the LOI between two representatives of the RELs, namely, brain abscess and glioblastoma (GBM). The diagnostic ability of the selected parameters as predictors for the machine learning algorithms was assessed using two models, the k-NN model and the SVM model with a Gaussian kernel. With the k-NN machine learning method, 80% of the abscesses and 100% of the GBM were classified correctly at high accuracy. Similar results were obtained via the SVM method. The proposed assessment of the LOI offers a new approach for evaluating ADC maps obtained from different RELs and contributing to the standardization of the ADC map assessment.
High-grade gliomas are primary brain tumors with poor prognosis, despite surgical treatment followed by radiotherapy and concomitant chemotherapy. We present two cases of long-term survival in patients treated for high-grade glioma and concomitant prolonged bacterial wound infection. The first patient treated for glioblastoma IDH-wildtype had been without disease progression for 61 months from the first resected recurrence. Despite incomplete chemotherapy-induced myelosuppression in the second patient with anaplastic astrocytoma IDH-mutant, she died without disease relapse after 14 years from the diagnosis due to other comorbidities. We assume that the documented prolonged survival could be related to the bacterial infection.
- Publikační typ
- kazuistiky MeSH
Differential diagnosis of brain lesion pathologies is complex, but it is nevertheless crucial for appropriate clinical management. Advanced imaging methods, including diffusion-weighted imaging and apparent diffusion coefficient, can help discriminate between brain mass lesions such as glioblastoma, brain metastasis, brain abscesses as well as brain lymphomas. These pathologies are characterized by blood-brain barrier alterations and have been extensively studied. However, the changes in the blood-brain barrier that are observed around brain pathologies and that contribute to the development of vasogenic brain edema are not well described. Some infiltrative brain pathologies such as glioblastoma are characterized by glioma cell infiltration in the brain tissue around the tumor mass and thus affect the nature of the vasogenic edema. Interestingly, a common feature of primary and secondary brain tumors or tumor-like brain lesions characterized by vasogenic brain edema is the formation of various molecules that lead to alterations of tight junctions and result in blood-brain barrier damage. The resulting vasogenic edema, especially blood-brain barrier disruption, can be visualized using advanced magnetic resonance imaging techniques, such as diffusion-weighted imaging and apparent diffusion coefficient. This review presents a comprehensive overview of blood-brain barrier changes contributing to the development of vasogenic brain edema around glioblastoma, brain metastases, lymphomas, and abscesses.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The response of the blood-brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH. Supporting some of these beneficial cascades while attenuating the major pathophysiological pathways might be decisive in inhibiting the negative impact of bleeding in the subarachnoid space. In this review, we attempt a comprehensive overview of the current knowledge on the molecular and cellular changes in the BBB following SAH and their possible modulation by various drugs and substances.
Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.
- MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- intrakraniální vazospazmus farmakoterapie etiologie patofyziologie MeSH
- ischemie mozku farmakoterapie etiologie patofyziologie MeSH
- lidé MeSH
- nimodipin terapeutické užití MeSH
- randomizované kontrolované studie jako téma metody MeSH
- subarachnoidální krvácení komplikace farmakoterapie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Subarachnoid hemorrhage is a specific, life-threatening form of hemorrhagic stroke linked to high morbidity and mortality. It has been found that the choroid plexus of the brain ventricles forming the blood-cerebrospinal fluid barrier plays an important role in subarachnoid hemorrhage pathophysiology. Heme oxygenase-1 and biliverdin reductase are two of the key enzymes of the hemoglobin degradation cascade. Therefore, the aim of present study was to investigate changes in protein levels of heme oxygenase-1 and biliverdin reductase in the rat choroid plexus after experimental subarachnoid hemorrhage induced by injection of non-heparinized autologous blood to the cisterna magna. Artificial cerebrospinal fluid of the same volume as autologous blood was injected to mimic increased intracranial pressure in control rats. Immunohistochemical and Western blot analyses were used to monitor changes in the of heme oxygenase-1 and biliverdin reductase levels in the rat choroid plexus after induction of subarachnoid hemorrhage or artificial cerebrospinal fluid application for 1, 3, and 7 days. We found increased levels of heme oxygenase-1 and biliverdin reductase protein in the choroid plexus over the entire period following subarachnoid hemorrhage induction. The level of heme oxygenase-1 was the highest early (1 and 3 days) after subarachnoid hemorrhage indicating its importance in hemoglobin degradation. Increased levels of heme oxygenase-1 were also observed in the choroid plexus epithelial cells at all time points after application of artificial cerebrospinal fluid. Biliverdin reductase protein was detected mainly in the choroid plexus epithelial cells, with levels gradually increasing during subarachnoid hemorrhage. Our results suggest that heme oxygenase-1 and biliverdin reductase are involved not only in hemoglobin degradation but probably also in protecting choroid plexus epithelial cells and the blood-cerebrospinal fluid barrier from the negative effects of subarachnoid hemorrhage.
- Publikační typ
- časopisecké články MeSH
The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.
- MeSH
- homeostáza fyziologie MeSH
- lidé MeSH
- mozkomíšní mok metabolismus MeSH
- nemoci centrálního nervového systému * imunologie metabolismus patofyziologie MeSH
- plexus chorioideus anatomie a histologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
