RESUMO
Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis.
Assuntos
Cavidades Cranianas/imunologia , Cavidades Cranianas/fisiologia , Dura-Máter/imunologia , Dura-Máter/fisiologia , Animais , Apresentação de Antígeno/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos/líquido cefalorraquidiano , Senescência Celular , Quimiocina CXCL12/farmacologia , Dura-Máter/irrigação sanguínea , Feminino , Homeostase , Humanos , Imunidade , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Células Estromais/citologia , Linfócitos T/citologiaRESUMO
Classical monocytes (CMs) are ephemeral myeloid immune cells that circulate in the blood. Emerging evidence suggests that CMs can have distinct ontogeny and originate from either granulocyte-monocyte- or monocyte-dendritic-cell progenitors (GMPs or MDPs). Here, we report surface markers that allowed segregation of murine GMP- and MDP-derived CMs, i.e., GMP-Mo and MDP-Mo, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP-Mo yielded an equal increase in homeostatic CM progeny, such as blood-resident non-classical monocytes and gut macrophages; however, these cells differentially seeded various other selected tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo differentiated into distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse that differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.
Assuntos
Diferenciação Celular , Macrófagos , Monócitos , Animais , Monócitos/imunologia , Monócitos/citologia , Camundongos , Diferenciação Celular/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Pulmão/citologia , Pulmão/imunologia , Homeostase , Camundongos Endogâmicos C57BL , Células Dendríticas/imunologia , Linhagem da Célula , Transferência AdotivaRESUMO
The central nervous system (CNS) has been viewed as an immunologically privileged site, but emerging works are uncovering a large array of neuroimmune interactions primarily occurring at its borders. CNS barriers sites host diverse population of both innate and adaptive immune cells capable of, directly and indirectly, influence the function of the residing cells of the brain parenchyma. These structures are only starting to reveal their role in controlling brain function under normal and pathological conditions and represent an underexplored therapeutic target for the treatment of brain disorders. This review will highlight the development of the CNS barriers to host neuro-immune interactions and emphasize their newly described roles in neurodevelopmental, neurological, and neurodegenerative disorders, particularly for the meninges.
Assuntos
Encéfalo , Doenças Neurodegenerativas , Sistema Nervoso Central , Humanos , Meninges , NeuroimunomodulaçãoRESUMO
The central nervous system (CNS) has historically been viewed as an immunologically privileged site, but recent studies have uncovered a vast landscape of immune cells that reside primarily along its borders. While microglia are largely responsible for surveying the parenchyma, CNS barrier sites are inhabited by a plethora of different innate and adaptive immune cells that participate in everything from the defense against microbes to the maintenance of neural function. Static and dynamic imaging studies have revolutionized the field of neuroimmunology by providing detailed maps of CNS immune cells as well as information about how these cells move, organize, and interact during steady-state and inflammatory conditions. These studies have also redefined our understanding of neural-immune interactions at a cellular level and reshaped our conceptual view of immune privilege in this specialized compartment. This review will focus on insights gained using imaging techniques in the field of neuroimmunology, with an emphasis on anatomy and CNS immune dynamics during homeostasis, infectious diseases, injuries, and aging.
Assuntos
Sistema Nervoso Central , Neuroimunomodulação , Homeostase , HumanosRESUMO
Administration of a nitric oxide (NO) donor triggers migraine attacks, but the mechanisms by which this occurs are unknown. Reactive nitroxidative species, including NO and peroxynitrite (PN), have been implicated in nociceptive sensitization, and neutralizing PN is antinociceptive. We determined whether PN contributes to nociceptive responses in two distinct models of migraine headache. Female and male mice were subjected to 3 consecutive days of restraint stress or to dural stimulation with the proinflammatory cytokine interleukin-6. Following resolution of the initial poststimulus behavioral responses, animals were tested for hyperalgesic priming using a normally non-noxious dose of the NO donor sodium nitroprusside (SNP) or dural pH 7.0, respectively. We measured periorbital von Frey and grimace responses in both models and measured stress-induced changes in 3-nitrotyrosine (3-NT) expression (a marker for PN activity) and trigeminal ganglia (TGs) mitochondrial function. Additionally, we recorded the neuronal activity of TGs in response to the PN generator SIN-1 [5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride]. We then tested the effects of the PN decomposition catalysts Fe(III)5,10,15,20-tetrakis(N-methylpyridinium-4-yl) porphyrin (FeTMPyP) and FeTPPS [Fe(III)5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato chloride], or the PN scavenger MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin] against these behavioral, molecular, and neuronal changes. Neutralizing PN attenuated stress-induced periorbital hypersensitivity and priming to SNP, with no effect on priming to dural pH 7.0. These compounds also prevented stress-induced increases in 3-NT expression in both the TGs and dura mater, and attenuated TG neuronal hyperexcitability caused by SIN-1. Surprisingly, FeTMPyP attenuated changes in TG mitochondrial function caused by SNP in stressed males only. Together, these data strongly implicate PN in migraine mechanisms and highlight the therapeutic potential of targeting PN.SIGNIFICANCE STATEMENT Among the most reliable experimental triggers of migraine are nitric oxide donors. The mechanisms by which nitric oxide triggers attacks are unclear but may be because of reactive nitroxidative species such as peroxynitrite. Using mouse models of migraine headache, we show that peroxynitrite-modulating compounds attenuate behavioral, neuronal, and molecular changes caused by repeated stress and nitric oxide donors (two of the most common triggers of migraine in humans). Additionally, our results show a sex-specific regulation of mitochondrial function by peroxynitrite following stress, providing novel insight into the ways in which peroxynitrite may contribute to migraine-related mechanisms. Critically, our data underscore the potential in targeting peroxynitrite formation as a novel therapeutic for the treatment of migraine headache.
Assuntos
Transtornos de Enxaqueca , Ácido Peroxinitroso , Ratos , Humanos , Camundongos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Doadores de Óxido Nítrico , Óxido Nítrico , Cloretos , NitroprussiatoRESUMO
Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1ß and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure.
Assuntos
Citocinas , Interleucina-4 , Macrófagos , Animais , Ratos , Anti-Inflamatórios , Citocinas/líquido cefalorraquidiano , Dura-Máter , Doenças Neuroinflamatórias , Animais Recém-NascidosRESUMO
BACKGROUND AND PURPOSE: An increasing number of cases of iatrogenic cerebral amyloid angiopathy (CAA) have now been reported worldwide. Proposed diagnostic criteria require a history of medical intervention with potential for amyloid-ß transmission, for example those using cadaveric dura mater or requiring instrumentation of the brain or spinal cord. Clinical presentation occurs after an appropriate latency (usually three or four decades); to date, most patients with iatrogenic CAA have had 'early-onset' disease (compared to sporadic, age-related, CAA), as a consequence of childhood procedures. RESULTS: We describe five cases of possible iatrogenic CAA in adults presenting in later life (aged 65 years and older); all had prior neurosurgical interventions and presented after a latency suggestive of iatrogenic disease (range 30-39 years). Use of cadaveric dura mater was confirmed in one case, and highly likely in the remainder. CONCLUSION: The presentation of iatrogenic CAA in older adults widens the known potential spectrum of this disease and highlights the difficulties of making the diagnosis in this age group, and particularly in differentiating iatrogenic from sporadic CAA. Increased vigilance for cases presenting at an older age is essential for furthering our understanding of the clinical phenotype and broader implications of iatrogenic CAA.
Assuntos
Angiopatia Amiloide Cerebral , Doença Iatrogênica , Humanos , Angiopatia Amiloide Cerebral/complicações , Idoso , Feminino , Masculino , Idoso de 80 Anos ou maisRESUMO
Eosinophilic angiocentric fibrosis (EAF) is a rare, benign fibroinflammatory condition primarily affecting the sinonasal and upper respiratory tract, with a few cases reported beyond these regions. Primary intracranial EAF is rare. To date, only one case of intracranial EAF has been reported; ours is the second. This case report presents a case of EAF in a 55-year-old man, initially misdiagnosed as meningioma based on clinical and radiological features. The patient complained of a persistent dull headache for six months without associated neurological symptoms. Brain magnetic resonance imaging revealed a dural-based lesion with characteristics suggestive of meningioma. However, histopathological examination post-surgical resection revealed a nodular vascular lesion with concentric angiocentric fibrosis, a distinctive onion skin pattern, and an inflammatory infiltrate rich in eosinophils, plasma cells, and histiocytes. Immunohistochemistry ruled out IgG4-related disease, and other systemic disorders were ruled out based on combined clinical and histological features. This case underscores the need for considering EAF in the differential diagnosis of dural-based lesions. Awareness of its potential mimicking of meningioma is crucial for accurate diagnosis and appropriate management, emphasizing the importance of histopathological examination in challenging cases.
RESUMO
This Article provides a concise summary of the comprehensive exploration into the dura mater, dural tears, and the groundbreaking medical device, ArtiFascia® Dura Substitute. The neuroanatomy of the dura mater is elucidated, emphasizing its resilience and susceptibility to tears during spinal surgery. Dural repair methods are scrutinized, with research findings revealing the efficacy of primary closure with or without a patch.The introduction of ArtiFascia®, a nanofiber-based resorbable dural repair graft, represents a pivotal moment in neurosurgery. Obtaining 510(k) clearance from the FDA, ArtiFascia® demonstrates exceptional biological benefits, including enhanced cellular adhesion and tissue regeneration. The device's safety is affirmed through chemical analysis and toxicological risk assessment.The NEOART study, a randomized clinical trial involving 85 subjects across prominent European medical centers, validates ArtiFascia®'s superiority over existing dural substitutes. Noteworthy findings include exceptional graft strength, durability, and its ability to withstand physiological pressures.In conclusion, ArtiFascia® marks a revolutionary era in neurosurgery, promising safer and more effective solutions. This innovative device has the potential to elevate standards of care, offering both patients and surgeons an improved experience in navigating the complexities of neurosurgical procedures. The abstract encapsulates the key elements of the research, emphasizing the transformative impact of ArtiFascia® in the field.
Assuntos
Dura-Máter , Procedimentos Neurocirúrgicos , Humanos , Dura-Máter/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neurocirurgia/métodos , NanofibrasRESUMO
Cerebrospinal fluid (CSF) circulation is considered the third circulation of the human body. Recently, some scholars have proposed the myodural bridge (MDB) as a novel power source for CSF flow. Moreover, the suboccipital muscles can exert a driving force on the CSF via the MDB. This hypothesis is directly supported by head rotation and nodding movements, which can affect CSF circulation. The MDB has been validated as a normal structure in humans and mammals. In addition, the fusion of MDB fibers of different origins that act in concert with each other forms the MDB complex (MDBC). The MDBC may be associated with several CSF disorder-related neurological disorders in clinical practice. Therefore, the morphology of the MDBC and its influencing factors must be determined. In this study, T2-weighted imaging sagittal images of the cervical region were analyzed retrospectively in 1085 patients, and magnetic resonance imaging (MRI) typing of the MDBC was performed according to the imaging features of the MDBC in the posterior atlanto-occipital interspace (PAOiS) and posterior atlanto-axial interspace (PAAiS). The effects of age and age-related degenerative changes in the cervical spine on MRI staging of the MDBC were also determined. The results revealed four MRI types of the MDBC: type A (no MDBC hyposignal shadow connected to the dura mater in either the PAOiS or PAAiS), type B (MDBC hyposignal shadow connected to the dura mater in the PAOiS only), type C (MDBC hyposignal shadow connected to the dura mater in the PAAiS only), and type D (MDBC hyposignal shadow connected to the dura mater in both the PAOiS and PAAiS). The influencing factors for the MDBC typing were age (group), degree of intervertebral space stenosis, dorsal osteophytosis, and degenerative changes in the cervical spine (P < 0.05). With increasing age (10-year interval), the incidence of type B MDBC markedly decreased, whereas that of type A MDBC increased considerably. With the deepening of the degree of intervertebral space stenosis, the incidence of type C MDBC increased significantly, whereas that of type A MDBC decreased. In the presence of dorsal osteophytosis, the incidence of type C and D MDBCs significantly decreased, whereas that of type A increased. In the presence of protrusion of the intervertebral disc, the incidence of type B, C, and D MDBCs increased markedly, whereas that of type A MDBC decreased considerably, with cervical degenerative changes combined with spinal canal stenosis. Moreover, the incidence of both type C and D MDBCs increased, whereas that of type A MDBC decreased. Based on the MRI signal characteristics of the dural side of the MDBC, four types of the MDBC were identified. MDBC typing varies dynamically according to population distribution, depending on age and cervical degeneration (degree of intervertebral space stenosis, vertebral dorsal osteophytosis formation, simple protrusion of intervertebral disc, and cervical degeneration changes combined with spinal canal stenosis, except for the degree of protrusion of the intervertebral disc and the degree of spinal canal stenosis); however, it is not influenced by sex.
Assuntos
Músculos do Pescoço , Pescoço , Animais , Humanos , Constrição Patológica , Estudos Retrospectivos , Pescoço/anatomia & histologia , Músculos do Pescoço/anatomia & histologia , Vértebras Cervicais/anatomia & histologia , Dura-Máter/anatomia & histologia , Imageamento por Ressonância Magnética , MamíferosRESUMO
BACKGROUND: Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among young people and is a matter of concern for forensic pathologists. Many authors have tried to estimate a person's survival time (ST) after TBI using different approaches. OBJECTIVE: The present study aimed to present an innovative workflow to estimate the ST after TBI by observing the inflammatory reaction of the dura mater (DM). METHODS: The authors collected DM samples from 36 cadavers (20 with TBI and 16 with no history or signs of TBI). Each sample was labelled via immunohistochemistry with three different primary antibodies, CD15, CD68, and CD3, yielding 108 slides in total. The slides were digitalized and analysed using QuPath software. RESULTS: The DM is involved in the inflammatory response after TBI. CD15 immunoreactivity allowed us to distinguish between subjects who died immediately after TBI and those with an ST of minutes or hours. CD3 immunoreactivity can be used to differentiate subjects with an ST of days from those with other STs. Moreover, the DM samples showed an acceptable diagnostic yield even in samples with signs of putrefaction.
RESUMO
In neurosurgical interventions, effective closure of the dura mater is essential to prevent cerebrospinal fluid leakage and minimize post-operative complications. Biodegradable synthetic materials have the potential to be used as dura mater grafts owing to their regenerative properties and low immunogenicity. This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The stained slides were graded based on the brain-specific reactions. The results showed no damage to the underlying brain tissue for either the ArtiFascia or control implants. Neither inflammation nor neuronal loss was evident, corroborating the safety of the ArtiFascia. This approach, combined with previous histopathological analyses, strengthens the safety profile of ArtiFascia and sets a benchmark for biodegradable material assessment in dura graft applications. This study aligns with the Food and Drug Administration guidelines and offers a comprehensive evaluation of the potential neural tissue effects of synthetic dura mater grafts.
RESUMO
The article presents an analysis of the plastic reconstructive surgery effectiveness for patients with an extended tracheal defect using an allograft based on the dura mater (DM) at the final stage of surgical treatment of laryngeal and tracheal cicatricial stenosis. The study included 20 patients with cicatricial stenosis of the larynx and trachea, who were previously performed plastic reconstructive treatment with scar tissue excision in the lumen of the respiratory tract and restoration of the supporting frame of the larynx and trachea using allografts based on costal allocartilage. The age of the patients ranged from 21 to 54 years, the duration of the disease was from 1 to 5 years. After a standard clinical and laboratory examination, with a mandatory video endoscopic examination of the larynx and trachea, multislice computed tomography of the larynx and trachea, patients underwent plastic closure of the tracheal defect using DM. Dynamic outpatient monitoring was carried out once a week for 1 month, once a month for 3 months, control examination was done 6 months after surgical treatment. The results of the study demonstrated a full-fledged social and labor rehabilitation of all 20 patients after the final stage of surgical treatment using DM, the absence of rejection reaction and migration of allo-implantation material, the preserved lumen of the larynx and trachea with a rigid supporting skeleton and the absence of anterior tracheal wall floatation. The use of DM as an additional strengthening of the anterior tracheal wall for patients with deficiency of muscular aponeurotic tissues and more than 2 cm size tracheal defect is highly effective at the final stage of surgical treatment for plastic closure of the tracheal defect.
Assuntos
Cicatriz , Dura-Máter , Laringoestenose , Procedimentos de Cirurgia Plástica , Estenose Traqueal , Humanos , Adulto , Masculino , Feminino , Laringoestenose/cirurgia , Laringoestenose/etiologia , Procedimentos de Cirurgia Plástica/métodos , Pessoa de Meia-Idade , Estenose Traqueal/cirurgia , Estenose Traqueal/etiologia , Cicatriz/etiologia , Cicatriz/cirurgia , Dura-Máter/cirurgia , Resultado do Tratamento , Traqueia/cirurgia , Laringe/cirurgiaRESUMO
Dural sinuses were recently identified as a hub for peripheral immune surveillance of brain-derived antigens cleared through CSF. However, animal studies have also indicated that substances and cells may enter the intracranial compartment directly from bone marrow. We used MRI and a CSF tracer to investigate in vivo whether intracranial molecules can move via dura to skull bone marrow in patients with suspicion of CSF disorders. Tracer enrichment in CSF, dural regions and within skull bone marrow was assessed up to 48 h after intrathecal administration of gadobutrol (0.5 ml, 1 mmol/ml) in 53 patients. In participants diagnosed with disease, tracer enrichment within diploe of skull bone marrow was demonstrated nearby the parasagittal dura, nearby extensions of parasagittal dura into diploe, and in diploe of skull bone remote from the dura extensions. This crossing of meningeal and skull barriers suggests that bone marrow may contribute in brain immune surveillance also in humans.
Assuntos
Medula Óssea , Crânio , Animais , Dura-Máter , Cabeça , Humanos , Meninges/diagnóstico por imagem , Crânio/diagnóstico por imagemRESUMO
PURPOSE: To clarify the invasiveness to surrounding structures and recurrence rate of each subtype of nonfunctioning pituitary neuroendocrine tumor (Pit-NETs) according to the WHO 2022 classification. METHODS: This retrospective study utilized data from 292 patients with nonfunctioning Pit-NETs treated with initial transsphenoidal surgery. Recurrence was evaluated on 113 patients who were available for a magnetic resonance imaging follow-up ≥ 60 months. All tumors were assessed by immunohistochemical staining for Pit-1, T-PIT, and GATA3. Invasiveness to surrounding structures was evaluated based on intraoperative findings. RESULTS: Cavernous sinus invasion was found in 47.5% of null cell tumors, 50.0% of Pit-1 lineage tumors, 31.8% of corticotroph tumors, and 18.3% of gonadotroph tumors. Dura mater defects in the floor of sellar turcica, indicating dural invasion, were found in 44.3% of null cell tumors, 36.4% of corticotroph tumors, 16.7% of Pit-1 lineage tumors, and 17.3% of gonadotroph tumors. In logistic regression analysis, Pit-1 (OR 5.90, 95% CI 1.71-20.4, P = 0.0050) and null tumors (OR 4.14, 95% CI 1.86-9.23, P = 0.0005) were associated with cavernous sinus invasion. Recurrence was found in 8 (4.9%) patients, but without significant differences between tumor subtypes. The presence of cavernous sinus invasion was correlated with recurrence (HR = 1.95, 95% CI 1.10-3.46, P = 0.0227). CONCLUSION: Among nonfunctioning Pit-NETs, Pit-1 lineage tumors tend to invade the cavernous sinus, corticotroph tumors may produce dura mater defects, and null cell tumors tend to cause both. Pit-NETs with cavernous sinus invasion require a careful attention to recurrence.
Assuntos
Adenoma , Tumores Neuroendócrinos , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Invasividade Neoplásica/patologiaRESUMO
Spinal meningiomas are relatively rare, but account for a significant proportion of primary spinal tumors in adults. These meningiomas can be found anywhere along the spinal column and their diagnosis is often delayed due to their slow growth and the lack of significant neurological symptoms until they reach a critical size, at which point signs of spinal cord or nerve root compression generally manifest and progress. If left untreated, spinal meningiomas can cause severe neurological deficits including rendering patients paraplegic or tetraplegic. In this chapter we will review the clinical features of spinal meningiomas, their surgical management, and detail molecular features that differentiate them from intracranial meningiomas.
Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Medula Espinal , Adulto , Humanos , Neoplasias da Medula Espinal/diagnóstico , Coluna VertebralRESUMO
OBJECTIVE: The objective of this review was to describe the immunological changes that take place in the dura mater in response to metastatic disease that seeds the CNS. The authors hypothesized that the dura's anatomy and resident immune cell population play a role in enabling metastasis to the brain and leptomeninges. METHODS: An extensive literature search was conducted to identify evidence that supports the dura's participation in metastasis to the CNS. The authors' hypothesis was informed by a recent upsurge in studies that have investigated the dura's role in metastatic development, CNS infections, and autoimmunity. They reviewed this literature as well as the use of immunotherapy in treating brain metastases and how these therapies change the meningeal immune landscape to overcome and reverse tumor-promoting immunosuppression. RESULTS: Evidence suggests that the unique architecture and immune cell profile of the dura, compared with other immune compartments within the CNS, facilitate entry of metastatic tumor cells into the brain. Once these tumor cells penetrate the dural barrier, they propagate an immunosuppressive tumor microenvironment. Therefore, immunotherapy may serve to overcome this immunosuppressive environment and liberate proinflammatory immune cells in an effort to combat metastatic disease. CONCLUSIONS: Within the next few years, the authors expect the addition of several more scientific studies into the literature that further underscore the dura as a chief participant and neuroanatomical barrier in neuro-oncology.
Assuntos
Neoplasias Encefálicas , Neoplasias Supratentoriais , Humanos , Dura-Máter/patologia , Neoplasias Encefálicas/patologia , Encéfalo , Microambiente TumoralRESUMO
PURPOSE: Photosealing of many biological tissues can be achieved using a biocompatible material in combination with a dye that is activated by visible light to chemically bond over the tissue defect via protein cross-linking reactions. The aim of this study was to test the efficacy of photosealing using a commercially available biomembrane (AmnioExcel Plus) to securely close dural defects in comparison to another sutureless method (fibrin glue) in terms of repair strength. METHODS: Two-millimeter diameter holes were created in dura harvested from New Zealand white rabbits and repaired ex vivo using one of two methods: (1) in n = 10 samples, photosealing was used to bond a 6-mm-diameter AmnioExcel Plus patch over the dural defect, and (2) in n = 10 samples, fibrin glue was used to attach the same patch over the dural defect. Repaired dura samples were then subjected to burst pressure testing. Histological analysis was also performed of photosealed dura. RESULTS: The mean burst pressures of rabbit dura repaired with photosealing and fibrin glue were 302 ± 149 mmHg and 26 ± 24 mmHg, respectively. The increased repair strength using photosealing was statistically significant and considerably higher than the normal intracranial pressure of ~ 20 mmHg. Histology demonstrated a tight union at the interface between the dura surface and patch with no disruption of the dura structure. CONCLUSION: The results of this study suggest that photosealing performs better than fibrin glue for the fixation of a patch for ex vivo repair of small dural defects. Photosealing is worthy of testing in pre-clinical models for the repair of dural defects.
Assuntos
Materiais Biocompatíveis , Adesivo Tecidual de Fibrina , Animais , Coelhos , Materiais Biocompatíveis/uso terapêutico , Dura-Máter/cirurgia , Dura-Máter/patologiaRESUMO
Angiosarcoma is an uncommon, aggressive endothelial-cell tumor that usually affects the skin, and involvement of the skull is rare. Here, we describe a case of skull angiosarcoma associated with a calcified chronic subdural hematoma (CSDH). HIGHLIGHTSA very rare case of skull angiosarcoma associated with a calcified chronic subdural hematoma is presented.An asymptomatic subdural hematoma with an atypical history and radiological features should prompt further investigation.Contrast MRI images should to be obtained early to differentiate a subdural hematoma from other pathologies.
Assuntos
Hemangiossarcoma , Hematoma Subdural Crônico , Humanos , Hematoma Subdural Crônico/complicações , Hematoma Subdural Crônico/diagnóstico por imagem , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/cirurgia , Crânio , Cabeça , RadiografiaRESUMO
INTRODUCTION: While the calvarial sutures have a limited importance for the modern neurosurgeon, they were of considerable interest to cranial surgeons from the time of Hippocrates onwards. The reasons for this interest together with the evolution of ideas are the subjects of this paper. MATERIALS AND METHODS: The texts of surgeons from the time of Hippocrates to the eighteenth century have been studied and analysed. RESULTS: Hippocrates advised against trepanation through a suture without specifying why. Galen taught that the dura was only attached to the interior of the calvarium at the sutures. The first author to state that the attachment was diffuse was Berengario da Carpi, at the beginning of the sixteenth century. This teaching was subsequently ignored until the eighteenth century, from which time it has been universally accepted. It was also first emphasized in the eighteenth century that it was not dangerous to trepan at the sutures. CONCLUSIONS: This study documents the persistence of incorrect ideas from classical times to the middle of the eighteenth century. These notions would have limited the regions available for surgical access to the skull and thereby limited the benefits to be derived from surgery.