Production Of CSF Research Articles

Роль внутриклеточных сигнальных молекул в продукции гранулоцитарного КСФ мононуклеарными фагоцитами при стрессе и цитостатическом воздействии

Роль внутриклеточных сигнальных молекул в продукции гранулоцитарного КСФ мононуклеарными фагоцитами при стрессе и цитостатическом воздействии

PLEURAL EFFUSION FOLLOWING VENTRICULO-PLEURAL SHUNT PLACEMENT

SESSION TITLE: Fellows Disorders of the Pleura Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Ventriculo-pleural shunts (VPLS), is an alternative management of hydrocephalus, where excess cerebrospinal fluid is drained to the pleural cavity. Imbalances between production and absorption of CSF will lead to the accumulation and development of pleural effusion. We describe a case of a pleural effusion related to a VPLS. CASE PRESENTATION: A 42 year old female with CSF leak managed by VPLS, previous STEMI with stent placement, and asthma, presented with retrosternal, right chest discomfort and dyspnea. Dyspnea began four months prior, and a right-sided thoracentesis had been performed two weeks earlier. Her pulmonologist previously noted small chronic pleural effusions insufficient for thoracentesis. From her previous thoracentesis, cultures were negative and cytology showed chronic inflammation. Cell profile, LDH, and protein were not tested. Subsequent thoracentesis yielded 165 WBC, <2000 RBC, 25 neutrophils, 39 lymphocytes. Cultures were negative and cytology showed acute and chronic inflammation. The fluid was transudative with an LDH of 109 U/L and a protein of 1.6 g/dL. She underwent a revision of her shunt to the peritoneal cavity. DISCUSSION: Extra-cranial shunts are used to divert CSF into an extracerebral compartment to relieve symptoms associated with hydrocephalus. The most widely used locations for shunt placement are the peritoneum and atrium. VPLS is an alternative when a peritoneal or atrial shunt is not suitable. This could be due to adhesions, infection, thrombosis or obliteration.(1) VPLS has a 7% complication rate and includes obstruction (functional or structural), pleural effusion, and pneumothorax.(2) The most common are pleural effusions; typically occurring within the first year of placement. Pleural fluid reabsorption by parietal lymphatics is estimated to be around 0.15 ml/k/h. This can increase as a response to increased pleural fluid filtration. Pleural effusions occur when filtration exceeds the maximum pleural lymph flow, typically 30 ml/kg/h.(3) The pleural fluid analysis shows a transudative effusion resembling CSF, but exudative effusions may also occur in chronic inflammation. Mild cases may resolve without intervention. Symptomatic cases with moderate or recurrent effusions may require thoracentesis, chest tube insertion, and occasionally shunt revisions (4). CONCLUSIONS: The pleural cavity is an alternative to peritoneal and atrial shunts for drainage of CSF in the treatment of refractory hydrocephalus. Pleural effusion is the most common complication typically occurring within the first year. While mild cases are self-limited, moderate or recurrent effusions will require intervention such as thoracentesis, chest tube insertion or possibly shunt revision. Reference #1: Ransohoff J. Ventriculopleural anastomosis in treatment of midline obstructed masses. J Neurosurg. 1954;11:295–301 Reference #2: Donald P. Megison & Edward C. Benzel (1988) Ventriculo-pleural Shunting for Adult Hydrocephalus, British Journal of Neurosurgery, 2:4, 503-505, DOI: 10.3109/02688698809029605 Reference #3: Miserocchi, G. “Physiology and Pathophysiology of Pleural Fluid Turnover.” European Respiratory Journal, vol. 10, no. 1, 1997, pp. 219–225., DOI:10.1183/09031936.97.10010219. DISCLOSURES: No relevant relationships by Sarah Cheyney, source=Web Response No relevant relationships by Gurjot Garcha, source=Web Response No relevant relationships by Ahmed Khan, source=Web Response No relevant relationships by Albert Magh, source=Web Response No relevant relationships by Crystal Verdick, source=Web Response

Involvement of Signaling Cascades in Granulocytopoiesis Regulation under Conditions of Cytostatic Treatment

Suppression of the production of granulocytic CSF under the effect of 5-fluorouracyl is related to disorders in the NF-κB-, cAMP-dependent signaling pathways and MAPK cascade. These secondary messengers are involved in the regulation of functional activity of nonadherent myelokaryocytes starting from day 10 of the experiment (initial period of the hemopoietic granulocytic stem regeneration after antimetabolite challenge). Granulocytic CSF does not play essential role in the formation of colony-stimulating activity of cells of the adherent and nonadherent fractions of the bone marrow. Only cAMP-dependent pathway is involved in the regulation of the realization of the granulocytic precursor growth potential in response to the challenge.

Examining perinatal subdural haematoma as an aetiology of extra-axial hygroma and chronic subdural haematoma.

AimBenign external hydrocephalus (BEH), hygroma and chronic subdural haematoma are extra‐axial fluid collections in infants. MRI studies have shown that almost half of all new‐borns have perinatal subdural blood, generally referred to as subdural haematoma (SDH) or perinatal SDH. Epidemiologically there are striking similarities between chronic SDH and BEH in infants.MethodsDiscussion of pathophysiological mechanisms for BEH and chronic SDH, based on existing literature.ResultsPerinatal SDH is common, and we hypothesise that this condition in some infants develop into extra‐axial fluid collections, known as hygroma, BEH or chronic subdural haematoma. The mechanism seems to be an intradural bleeding that creates an obstructive layer preventing normal CSF absorption. The site where the bleeding originates from and those areas enveloped in blood from the primary damaged area are prone to later rebleeds, seen as ‘acute on chronic’ haematomas. With steady production of CSF and the blockage, increased intracranial pressure drives the accelerated skull growth seen in many of these children.ConclusionPerinatal SDH hampers CSF absorption, possibly leading to BEH and chronic SDH, with a high risk of false accusations of abuse. Close monitoring of head circumference could prove vital in detecting children with this condition.

Congenital Hydrocephalus in a Calf and its Surgical Treatment: A Case Report

Hydrocephalus is an accumulation of excessive fluid in durameter or ventricles of the brain (Purohit et al., 2012) thereby leading to the swelling of the cranium. It is mainly due to abnormal development of the fetus duringpregnancy; however, hereditary, infectious, and nutritional factors can also predispose this condition. This condition has been reported occasionally in the ewe, doe, mare, and sow, whilst it is rarely seen in cattle and buffalo 2001). Hydrocephalus occurs mainly due to three reasons, as excessive production of CSF, defective absorption of CSF,and interference in the passage of CSF. Hydrocephalus may cause increased intracranial cerebral pressure, progressive enlargement of the head, convulsions, mental disability, and even death. This communication describes a case of congenital hydrocephalous in a day-old female cattle calf.

The Neuroimaging Studies in Children with Ventriculoperitoneal Shunt Complications: A 10 Years Descriptive Sudy in Tehran.

Background: Any mismatch between the production and absorption of CSF results in hydrocephalus. In most cases, the selected choice of treatment is the ventriculoperitoneal shunt insertion. Although, the surgery could have complications such as infection, shunt malfunction, subdural hematoma, seizure and Shunt immigration; so, the early and proper detection of these complications could result in better prognosis. The aim of this study was to evaluate and compare the efficacy of CT scan, CSF analysis and X-ray radiography in detection of shunt complications and problems in shunt placement and further follow-up in hospitalized children.Methods:The medical records of children in Rasul Akram hospital in Tehran were reviewed retrospectively in the last 10 years, from 2006 to 2016. All data were recorded in the prepared form including the age, sex, shunt complication, CT scan and CSF characteristics.Results:The total number of 95 patients were interfered in this study including 56 males (58.9%) and 39 females (41.1%). The mean age at the onset of complications were 2.8±2.2 years-old. The shunt obstruction (60%) and infection (25.3%) were the most common complications. The CT scan was able to detect 36.5% of shunt complications. The CT scan had the sensitivity and specificity of 50 and 87%, respectively in detection of shunt obstruction. The all cases of brain hematoma and hemorrhage were revealed by CT scan. On the other hand, the CT scan had 20% of sensitivity and 60% of specificity in the detection of shunt infection. The CSF evaluation in shunt infection revealed 92% hypoglycemia, 87.5% pleocytosis, and 62.5% positive CSF culture. CSF had the sensitivity, specificity, positive predictive value and negative predictive value of 92, 82, 63 and 97%, respectively. The patient's symptoms and signs were helpful in obtaining higher test accuracy.Conclusion: The CT scan was not a good sensitive and specific study in the detection of shunt obstruction and infection, but it was very accurate in detection of hemorrhage and hematoma. On the other hand, CSF evaluation was a reliable test in shunt infection disclosure.

Brain-Choroid Plexus Chemistry Changes Linkable to Caffeine Ingestion and Accompanying Short-Term Memory Disturbances in Experimental Models

A number of literatures have reported that caffeine could have negative effects on mental health and brain structures and chemistry. There are also reported positive effects of caffeine, such as improvement in memory, especially for those who consume caffeine from its natural sources. Sixty male juvenile Wistar rats were grouped into six (6) groups of 10 rats in each. The groups were labeled A-F with group A being the control group and groups B, C, D, E, and F being the treated groups. This investigation complements our previous efforts to study the effects of caffeine on the choroid plexus microscopic structure, which is involved in the production of the cerebrospinal fluids. Caffeine alters the activities of key enzymes that are associated with the production of CSF. This showed that the structural changes have observable alterations of the brain chemistry. Also, memory, a major attribute of mental power was tested in the same models; results showed that caffeine affected the short term memories. The effects of caffeine was studied in models that ingested caffeine solely and in other modeled after human use by consuming it with honey, a natural antioxidant rich sweetener. In this study, it was observed that the long-term consumption and high amount of caffeine increased the expression of carbonic anhydrase enzyme in the choroid plexus, this enzyme plays a major role in the production of CSF. In the caffeine-treated rats, there was also increased expression of Na+/K+-ATPase which may be associated with changes in the choroid epithelial cells. Honey improved the glutathione peroxidase level. Results showed the use of caffeine with honey had positive effects against the observed effects caused by ingestion of caffeine only. This also showed that caffeine use effects would vary in users of pure caffeine as mere drugs; and habitual consumers as beverages. Generally, evidences lead us to conclude that alterations in enzymes activities are associated with choroid plexus changes that could affect CSF production. These effects are also associated with behavioural changes.

Management and functional outcome of childhood hydrocephalus at the Kenyatta National Hospital

Background: Hydrocephalus is a pathological condition caused by abnormalities of production or absorption of CSF in the brain. The goal of this study was to evaluate the current management and outcome of children (aged 13 years and below) who were treated for hydrocephalus in a single institution in Kenya.Methods: A retrospective analysis was conducted on 200 childrenwho were admitted to the neurosurgical unit at the Kenyatta National Hospital and diagnosed with hydrocephalus between January 2000 and April 2013. The records were analyzed for demographic characteristics, clinical presentation and management variables. Outcome was assessed according to the Glasgow Outcome Scale (GOS) score at the time of discharge from hospital.Results: There were 95 male (47.5%) and 105 female (52.5%) patients. The median age was 3.5 months. 16.5% had associated congenital anomalies, the commonest being spina bifida (18.2%) and dandy walker cyst (18.2%). 162 (81%) of the patients had surgical intervention which included shunts (92.6%), drains (0.6%), therapeutic aspiration (0.6%) and endoscopic third ventriculostomy (6.2%). Good functional recovery was achieved by 94.6% patients whereas residual disabilities accounted for 0.6% and mortality accounted for 4.8%.Conclusion: Outcome depended on initial AVPU score, admission into our Intensive Care Unit and type of management. Surgical management resulted in better outcome but vigilant monitoring for shunt complications is warranted. We recommend follow-up studies using population-based longitudinal data and quantitative quality-of-life measures to identify the specific long-term outcomes including the individual and social impacts of childhood hydrocephalus in Africa.Keywords: Functional outcome, Hydrocephalus, Pediatric neurosurgery

Spontaneous rupture of congenital hydrocephalous: a rare complication

Hydrocephalous represents a diverse group of conditions that result from impaired circulation and/or absorption of CSF, or in rare circumstances, from increased production of CSF by choroid plexus papilloma. Hydrocephalous could be classified as communicating and non communicating. Hydrocephalous resulting from obstruction within ventricular system is called obstructive or non communicating hydrocephalous whereas that resulting from obliteration of subarachanoid cisterns or malfunction of arachanoid villi is called communicating or non obstructive hydrocephalous. Both forms can be congenital or acquired. The first surgical treatment reported in literature was performed by Hippocrates in 5th century B.C., who punctured the lateral ventricle in a patient with obstructive HC. Several procedures and devices have been developed since then, such as external ventricular drainage, external lumbar drainage, repeated lumbar puncture, Ommaya reservoir insertion, or ventriculosubgaleal diversion, ventriculoperitoneal and ventriculoatrial shunts.In untreated cases, head size may continue to increase. Spontaneous external rupture of hydrocephalous is rare presentation. Very few cases have been reported till date.

Choroid plexus--CSF system: Recent developments and clinical correlations.

The choroid plexus is a villous epithelial–endothelial vascular structure located within the ventricular system and is primarily responsible for the production of CSF. The choroid plexus–CSF system is crucial for the development, maintenance, and function of the CNS. The choroid plexus consists of a monolayer of cuboidal epithelial cells that surrounds a stromal core of connective tissue and capillaries. The choroid epithelium has a brush border consisting of microvilli; tight junctions, forming a blood–CSF barrier, join adjacent choroid epithelial cells.

Amyloid β Oligomers Disrupt Blood-CSF Barrier Integrity by Activating Matrix Metalloproteinases.

No treatments are yet available to cure Alzheimer's disease; however, soluble Aβ oligomers are believed to play a crucial role in the neuroinflammation that is observed in this disease. Here, we studied the effect of Aβ oligomers on the often neglected barrier between blood and brain, called the blood-CSF barrier (BCSFB). This BCSFB is formed by the choroid plexus epithelial cells and is important in maintaining brain homeostasis. We observed Aβ oligomer-induced changes in morphology and loss of BCSFB integrity that might play a role in Alzheimer's disease progression. Strikingly, both inhibition of matrix metalloproteinase (MMP) activity and MMP3 deficiency could protect against the detrimental effects of Aβ oligomer. Clearly, our results suggest that MMP inhibition might have therapeutic potential.

Involvement of NF-κB-dependent signaling and p38 MAPK signaling pathway in the regulation of hemopoiesis during restrain stress.

Protein kinase p38 was shown to contribute to the increase in production of granulocyte CSF by microenvironmental cells under conditions of restraint stress. Stimulation of colony-forming activity was not accompanied by the increase in maturation of clonogenic structures in the bone marrow granulocytic stem. This process was realized with the involvement of NF-κB-dependent signaling and p38 MAPK signaling pathway. Our study showed that the p38 MAPK signaling pathway plays an important role in the regulation of granulocytopoiesis, but not of erythropoiesis.

Endoscopic coagulation of choroid plexus hyperplasia

Hydrocephalus is a clinical disorder resulting from an imbalance between the production of CSF and its resorption, of which the latter is mostly a disadvantage. In rare cases of choroid plexus papilloma or carcinoma, hydrocephalus is due to an overproduction of CSF. Choroid plexus hyperplasia (CPH) is a distinct clinicopathological entity in which the enlarged choroid plexus produces large amounts of CSF. Historically, patients with CPH were treated by shunt procedures or by microsurgical removal of the choroid plexus, which is associated with a high complication rate. In this paper the authors show that endoscopic plexus coagulation can result in restoring the equilibrium of the intracranial fluid volumes, resulting in shunt independency. In this way, both the shunt-related complications and the bleeding risks of microsurgical plexectomy are avoided. In instances of hydrocephalus, thorough efforts should be made to demonstrate the underlying pathophysiology to choose the optimal treatment, of which shunt procedures should receive the least priority.

Multiplex Analysis of Cytokines, Chemokines, Growth Factors, MMP-9 and TIMP-1 Produced by Human Bone Marrow, Adipose Tissue, and Placental Mesenchymal Stromal Cells

Comparative analysis of mesenchymal stromal cells isolated from human BM, adipose tissue, and placenta was carried out. The cells were compared by the levels of constitutive, spontaneous, and LPS-induced production of Th1/proinflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-12, IL-17) and Th2/anti-inflammatory cytokines (IL-4, IL-5, IL-6, IL-10, IL-13), chemokines (IL-8, MCP-1, MIP-1β), growth factors (IL-7, granulocytic CSF, granulocytic macrophageal CSF, erythropoietin, VEGF, EGF, IGF-1, main FGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Mesenchymal stromal cells originating from different tissues were characterized by functional potential for hemopoiesis support (through production of granulocytic CSF, granulocytic macrophage CSF, erythropoietin), immunomodulation (through production of IFN-γ, IL-2, IL-6, IL-1β, TNF-α and chemokines IL-8, MCP-1, MIP-1β), and stimulation of reparative processes (through production of VEGF, FGF, IGF-1, IL-6 tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-9). By the type and levels of spontaneous (basal) production of cytokines, the adipose tissue mesenchymal stromal cells more distinctly demonstrated the proinflammatory (IL-1β TNF-α), immunoregulatory (IFN-γ, IL-2, IL-4, IL-6, IL-8, MCP-1, MIP-1β), and hemopoiesis-stimulating (granulocytic CSF, granulocytic macrophage CSF) phenotype and at the same time were characterized by lower sensitivity to lipopolysaccharide stimulation than BM and placental mesenchymal cells.

Management of postdural puncture headache with epidural blood patch in a child.

Management of postdural puncture headache with epidural blood patch in a child.

Fluo‐cAMP is transported by multidrug resistance‐associated protein isoform 4 in rat choroid plexus

The choroid plexuses (CP) are responsible for transport of micronutrients into brain and clearance of toxic compounds, in addition to its barrier function and production of CSF. Multidrug resistance-associated protein (Mrp) 4 is one transport protein highly expressed in CP tissue and is characterized as a versatile pump for toxicants and signalling molecules. Aim of the study was to determine transport characteristics of a fluorescent cAMP analog in rat CP and to define whether fluo-cAMP can be used for analyses of function, substrate/inhibitor specificity and regulation of Mrp4. Confocal imaging was used to analyze transport mechanisms in absence and presence of various modulators of organic anion transport in freshly isolated and functionally intact CP. Fluo-cAMP transport was saturable, selective, concentrative and metabolism-dependent, following an active two-step mechanism composed of apical uptake into epithelial cells and basolateral efflux. Uptake included a Na(+) -dependent and a Na(+) -independent component and was inhibited by estrone sulfate, taurocholate and sildenafil indicating involvement of organic anion transporting polypeptide Oatp1a5. Efflux was composed of an indirect Na(+) -dependent component and a component inhibitable by, for example, the MRP4 substrates/inhibitors, sulindac sulfide and 4-(2-aminoethyl) benzenesulfonyl fluoride. Therefore, fluo-cAMP can be used as fluorescent model compound for studying involvement of Mrp4 in signalling pathways and neuroprotection in CP.

Effects of Molecular Liposomal Hybrid Compositions with Oxidized Dextrans and Isonicotinic Acid Hydrazide on Production of Granulocytic Macrophage Colony-Stimulating Factor by Macrophages

The effects of molecular liposomal hybrid compositions consisting of liposomes (200-450 nm) containing oxidized dextrans (dextranals; 35-60 kDa) conjugated with isonicotinic acid hydrazide (dextrazides), their components, and native dextrans on the production of granulocytic macrophage CSF by peritoneal macrophages were studied in vitro. Dextranals proved to be more potent inductors of granulocytic macrophage CSF than native dextrans. Conjugation of nicotinic acid hydrazide with dextranals did not modify their capacity to stimulate the production of granulocytic macrophage CSF. Liposomes in the molecular liposomal hybrid compositions did not attenuate the dextrazide capacity to stimulate the production of granulocytic macrophage CSF. Molecular liposomal compositions containing 60 kDa dextrazide exhibited the most potent stimulatory effect on macrophage production of granulocytic macrophage CSF.

Regulation of cerebrospinal fluid production by caffeine consumption

BackgroundCaffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date.ResultsIn the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF). In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats.ConclusionThe results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.

Production of IL-10 by Human Natural Killer Cells Stimulated with IL-2 and/or IL-12

Human NK cell activity can be augmented in vitro by stimulation with IL-2 or IL-12, both of which also induce the production of IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF by NK cells. For the first time, we demonstrate that freshly purified NK cells stimulated with IL-2 proliferated and produced IL-10 in a dose-dependent manner. IL-10 mRNA expression, as detected by semiquantitative reverse transcription-PCR, reached peak levels at 24 h. IL-10 protein was detectable on day 2 and further increased on days 3 and 6 as measured by ELISA. However, IL-12 alone induced neither substantial proliferation nor detectable IL-10 production by fresh NK cells, but it synergized with IL-2 in inducing IL-10 mRNA expression and protein synthesis. IL-10 production by activated NK cells was confirmed by intracytoplasmic cytokine staining by three-color immunofluorescence of CD16+ and/or CD56+ NK cells with anti-IL-10 antibody. IL-10 production by NK cells was further confirmed in the NK-like cell line, YT, which constitutively expressed IL-10 mRNA and protein. IL-12 alone did not induce NK proliferation, but it inhibited IL-2-induced proliferation. Neutralization of endogenously produced IL-10 with anti-IL-10 antibodies did not overcome the inhibition of IL-2-induced proliferation by IL-12. Together, these results demonstrate that IL-2 and IL-12 synergize to induce IL-10 production by human NK cells and that IL-12 inhibits IL-2 induced NK cell proliferation by an IL-10-independent mechanism.

Colchicine down-regulates lipopolysaccharide-induced granulocyte-macrophage colony-stimulating factor production in murine macrophages.

Activation of macrophages by LPS and taxol results in production of IL-1, IL-6, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF), which are involved in regulating hemopoiesis, inflammation, and immune responses. Microtubules are proposed as a target site for LPS interaction(s), based on similarities between the effects of the tubulin-binding drug taxol and LPS. To clarify the role of microtubules in LPS-induced GM-CSF expression in macrophages, we examined whether microtubule depolymerizing agents affect GM-CSF production in macrophages. Pretreatment with colchicine impaired LPS induction of GM-CSF in RAW 264 cells, and studies using stable transfectants revealed that colchicine impaired the transcriptional responsiveness of a reporter gene driven by a GM-CSF promoter sequence. Colchicine inhibition of the GM-CSF response correlated with decreases in the mRNA levels of beta-tubulin; maximal inhibition of both events was observed 4 h after addition of colchicine. Microtubule agents inhibited LPS induction of IL-6 and TNF-alpha, while the induction of both IL-1beta and inducible nitric oxide synthase was unaltered, suggesting that LPS activates microtubule-dependent and -independent pathways. Interestingly, LPS stimulation of macrophages down-regulated levels of beta-tubulin transcripts, implying that LPS interacts with an element(s) of the microtubule network in vivo, activating pathways regulating transcription of beta-tubulin. The ability of both colchicine and LPS to modulate transcription of beta-tubulin suggests that this event does not per se underlie the inhibitory effect of colchicine on LPS-induced GM-CSF expression. These data led us to conclude that colchicine inhibits LPS induction of GM-CSF by affecting microtubule-dependent costimulatory signaling pathways that synergize with primary LPS-triggered responses.