Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.     

The importance of lymphatics in cerebrospinal fluid transport

Despite the fact that the central nervous system parenchyma does not contain lymphatics, extracranial lymphatic vessels play a very important role in volumetric cerebrospinal fluid (CSF) transport. The most important extracranial location at which lymphatics gain access to CSF is in the nasal submucosa after CSF convects through the cribriform plate. At relatively low intracranial pressures (ICPs), the majority of cranial CSF absorption occurs through this pathway. Global CSF transport parameters in the late gestation fetus and adult sheep are very similar, even though significant numbers of arachnoid projections seem to exist only in the adult. Therefore, extracranial lymphatic vessels play an important role in CSF transport before birth and may represent the primary mechanism for CSF absorption in the neonate. Based on these considerations, hydrocephalus may involve reduced CSF transport to, or into extracranial lymphatic absorption sites.     

Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?

Arachnoid villi and granulations are thought to represent the primary sites where cerebrospinal fluid (CSF) is absorbed. However, these structures do not appear to exist in the fetus but begin to develop around the time of birth and increase in number with age. With the use of a constant pressure-perfusion system in 2- to 6-day-old lambs, we observed that global CSF transport (0.012 +/- 0.003 ml x min(-1) x cmH(2)O(-1)) and CSF outflow resistance (96.5 +/- 17.8 cmH(2)O x ml(-1) x min) were very similar to comparable measures in adult animals despite the relative paucity of arachnoid villi at this stage of development. In the neonate, the recovery patterns of a radioactive protein CSF tracer in various lymph nodes and tissues indicated that CSF transport occurred through multiple lymphatic pathways. An especially important route was transport through the cribriform plate into extracranial lymphatics located in the nasal submucosa. To investigate the importance of the cribriform route in cranial CSF clearance, the cranial CSF compartment was isolated surgically from its spinal counterpart. When the cribriform plate was sealed extracranially under these conditions, CSF transport was impaired significantly. These data demonstrate an essential function for lymphatics in neonatal CSF transport and imply that arachnoid projections may play a limited role earlier in development.     

Lymphatic drainage of cerebrospinal fluid in mammals – are arachnoid granulations the main route of cerebrospinal fluid outflow?

The outflow of the cerebrospinal fluid (CSF) in animals was over the years the subject of detailed analysis. For a long time it was stated that arachnoid granulations of the venous sinuses play a key role in CSF circulation. However, recent studies on this subject have shown that a considerable part of the CSF is drained to the lymphatic vessels. Moreover, disorders in the CSF passage may result in severe central nervous system diseases such as e.g. hydrocephalus. In this paper, we summarize the current knowledge concerning the lymphatic drainage of the CSF in mammals. We present in detail comparative anatomy of different species taking into account cranial and spinal compartment. In addition, we clarified role of the lymphatic vessels in the CSF outflow and the relationship between impairment in this transport and central nervous system diseases. In the author’s opinion knowledge on CSF circulation is still poorly examined and therefore required comment.     

Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of 125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.     

Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus

It has been assumed that the pathogenesis of hydrocephalus includes a cerebrospinal fluid (CSF) absorption deficit. Because a significant portion of CSF absorption occurs into extracranial lymphatics located in the olfactory turbinates, the purpose of this study was to determine whether CSF transport was compromised at this location in a kaolin-induced communicating (extraventricular) hydrocephalus model in rats. Under 1-3% halothane anesthesia, kaolin (n = 10) or saline (n = 9) was introduced into the basal cisterns of Sprague-Dawley rats, and the development of hydrocephalus was assessed 1 wk later using MRI. After injection of human serum albumin ((125)I-HSA) into a lateral ventricle, the tracer enrichment in the olfactory turbinates 30 min postinjection provided an estimate of CSF transport through the cribriform plate into nasal lymphatics. Lateral ventricular volumes in the kaolin group (0.073 +/- 0.014 ml) were significantly greater than those in the saline-injected animals (0.016 +/- 0.001 ml; P = 0.0014). The CSF tracer enrichment in the olfactory turbinates (expressed as percent injected/g tissue) in the kaolin rats averaged 0.99 +/- 0.39 and was significantly lower than that measured in the saline controls (5.86 +/- 0.32; P < 0.00001). The largest degree of ventriculomegaly was associated with the lowest levels of lymphatic CSF uptake with lateral ventricular expansion occurring only when almost all of the lymphatic CSF transport capacity had been compromised. We conclude that lymphatic CSF absorption is impaired in a kaolin-communicating hydrocephalus model and that the degree of this impediment may contribute to the severity of the induced disease.     

Zur Feinstruktur der Arachnoidalzotten bei Mammalia

Zusammenfassung Arachnoidalzotten und Granula meningica von jungen und erwachsenen Katzen und Hunden wurden in situ über das Blutgefäßsystem mit Glutaraldehyd fixiert. Lichtmikroskopische Untersuchungen an Semidünnschnittserien und elektronenmikroskopische Auswertungen derselben Objekte ergaben: Die Arachnoidalzotten und Granula meningica von Hund und Katze zeigen den gleichen Feinbau. Die Unterschiede in der Größe und in der Struktur führen zu einer Klassifizierung der Arachnoidalzotten. Als Neurothelprotrusionen werden Einrichtungen des subduralen Neurothels beschrieben, die intradural Kontakt zu Duragefäßen aufnehmen oder transdural die Arachnoidea mit der Lamina intima der Wand des Sinus sagittalis superior verbinden. Die äußere Arachnoidalzellschicht ist an den Protrusionen unterschiedlich stark beteiligt. Die eigentlichen Arachnoidalzotten und Granula meningica haben immer einen Bindegewebsraum, der mit der Leptomeninx zusammenhängt. Flüssigkeit und Substanzen, die über die Arachnoidalzotten aus dem Subarachnoidalraum ausgeschieden werden, müssen folgende Zonen passieren. 1. das Mesothel des Subarachnoidalraumes, 2. den Bindegewebsraum der Arachnoidea, 3. die äußere Arachnoidalzellschicht, 4. das subdurale Neurothel, 5. den perivaskulären Bindegewebsraum, 6. das Endothel der Duragefäße oder die Wand des Sinus durae matris. Membranvesikulation, Endothelfensterung, Mikropinozytose, Systeme von Interzellularspalten der zellulären Scheiden und blind in der Zottenoberfläche endende Endothelkanälchen aus dem Sinus werden als morphologische Kriterien eines Stofftransportes angesehen, der für die Liquorresorption wichtig ist. Hierbei wird durch die aktive Steuerung der Zellen eine Diffusionsbarriere aufrechterhalten, die das milieu interne der Leptomeninx garantiert. Dieser Resorptionsweg über die Duragefäße (durale Liquorresorption) scheint die Resorption durch die Meninx vasculosa (piale Liquorresorption) und die mögliche Resorption über die intracerebralen Kapillaren (cerebrale Liquorresorption) zu ergänzen. Es wird vermutet, daß die Gefäße zusammen mit den Arachnoidalzotten eine Sonderfunktion bei der Liquorresorption erfüllen, die unter anderem den Aufgaben des Lymphgefäß-systems in der Peripherie ähnlich ist. Markhaltige und freie marklose Nervenfasern, die in der Zottenumgebung anzutreffen sind, könnten Pressoreceptoren für die Regulation des Liquordruckes sein. Es wird angenommen, daß die genannten Funktionen der Zotten in der Fetalzeit und Neugeborenen-Periode von der gesamten Arachnoidea und Dura erfüllt werden können.

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Summary Arachnoid villi and arachnoid granulations of young and adult cats and dogs were fixed in situ by glutaraldehyde perfusion through the Wood vessel system. Light microscopy of semi-thin serial sections and electron microscopic studies have given the following results: Arachnoidal villi and granulation of dogs and cats have identical ultrastructures. Differences in size and form characterise different types of arachnoid villi. Intradural and transdural protrusions of the subdural neurothelium are simple in structure. Most of these protrusions have contact with the perivascular sheaths of the dural blood vessels. The outer arachnoid cell layer has no or very little share in the cell plugs of the neurothelial protrusions. The larger type of the arachnoid villi and the arachnoid granulations contain a connective tissue space deriving from the leptomeninx. Fluid and substances which are to be secreted by the arachnoid villi from the subarachnoid space have to pass through six tissue laminae: 1. the mesothelium of the subarachnoid space, 2. the arachnoid connective tissue space, 3. the outer arachnoid cell layer, 4. the subdural neurothelium, 5. the perivascular connective tissue sheath, 6. the basement membrane and the endothelium of the dural vessel or sinus. Cytopempsis, endothelium fenestrations, micropinocytosis, complex-systems of intercellular gaps of the arachnoid cell border, and endothelium lined tubuli in the sinus wall are considered to show a specialized transport mechanism important for the CSF resorption. In this secretion process active cell mechanisms of the outer arachnoid cell layer and the subdural neurothelium probably guarantee the milieu interne of the leptomeninges. The cerebrospinal fluid (CSF) resorption through the dural blood vessels (dural resorption of CSF) seems to complete the main resorption within the meninx vasculosa (pial resorption of CSF) and the probable small resorption by intracerebral capillaries (cerebral resorption of CSF). It appears that the dural resorption of CSF through arachnoid villi may serve a special function similar to protein and antibody uptake in the peripheral connective tissue by lymphatic capillaries.Myelinated and unmyelinated free nerve fibers in the region of the villi may represent receptors of the liquor pressure control system. Within the fetal and perinatal period the whole arachnoidea and dura mater may fulfill the function of the later villi and granulations.

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Mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft.     

The anlage of the duodenal lymphatic bed: morphogenetic prerequisites, structure and importance

The anlage of the duodenal lymphatic bed takes place on the 3d month of the human intrauterine life. In the intestinal villi there are chyle sinuses, that fuse into presumptive lymphatic vessels, having capillary structure, when they get out of the villi. Intraorganic vessels turn into extraorganic ones, they flow into the pancreatoduodenal lymphatic vessels. In their lumens stromal anlage of the lymphatic nodes are formed as a result of invagination of the blood vessels. Development of the lymphatic bed in the duodenum preceded with formation of intestinal villi (this contributes to absorption of the intestinal content) and deformity of the superior mesenteric vein (this probably makes difficult the organ's drainage). The situation is solved owing to the lymphatic bed anlage. It is, evidently, formed by means of switching off a part of embryonal veins from the blood stream.     

Cytokeratin provides a specific marker for human arachnoid cells grown in vitro

Cells from cranial and spinal arachnoid membranes of humans were grown in culture. Their growth characteristics, morphology and details of their cytoskeletal composition are described. Arachnoid membranes, obtained at autopsy, were finely minced and incubated in tissue culture medium. Monolayers of cells of homogeneous morphology grew from these tissue fragments. The cells were flat and polygonal. They divided slowly to form non-overlapping monolayers of low cell density. Electron microscopic examination of cultured arachnoid cells revealed numerous desmosome-like tight junctions and abundant intermediate filaments (tonofilaments). Both morphological features are characteristic of arachnoid cells in situ, but not of cells in the fibroblast-rich dura mater. Immunofluorescence microscopy with monoclonal antibodies demonstrated cytokeratin in the cytoplasm of primary cultures of arachnoid cells. Thus we demonstrated that these cultured cells retained certain of the specific differentiated properties of arachnoid cells in situ and that they are not fibroblasts (which lack tight junctions and cytokeratins). To our knowledge, there have been no previous reports of in vitro growth of arachnoid cells. This in vitro model should be useful in studying the response of arachnoid cells to a variety of substances thought to be involved in the chronic inflammatory condition of the meninges known as arachnoiditis.     

A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical importance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in vertebrates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels.     

Lymphatic pump function in the inflamed gut

The role of the lymphatic circulation to actively remove fluid, cells, proteins, and other particles from the interstitium to prevent mounting edema is well appreciated, but whether and how this function is compromised during inflammation has been scarcely investigated. We discuss here the mechanisms of lymphatic pumping and their modulation in inflammatory conditions or by inflammatory mediators in the context of inflammatory bowel disease (IBD), an ensemble of disorders typically described with abnormal or dysfunctional intestinal or mesenteric lymphatic vessels. We report our findings showing impaired mesenteric lymphatic contractile activity in an animal model of intestinal inflammation that recapitulates some features of IBD and suggests a role for prostanoids in this dysfunction. With the knowledge that prostaglandin E(2) and prostacyclin are implicated in IBD pathogenesis and induce a potent inhibition of lymphatic pumping, we established the pharmacological profile for these prostaglandin receptors in mesenteric lymphatic vessels and their respective role in pumping inhibition. Inhibition of mesenteric lymphatic pumping during inflammation may be a cause of edema, compromised immune response, and granuloma associated with IBD.     

Causes and consequences of lymphatic disease

The visceral manifestations of lymphatic disorders (lymphangiomatosis and lymphangiectasia) are particularly severe. Any pathology of the lymphatic vasculature, whether superficial or internal, regional, or systemic, is predominated by the appearance of lymphedema, the characteristic form of tissue edema that occurs when lymphatic dysfunction supervenes. Disease manifestations may include dysregulation of body fluid homeostasis, immune traffic impairment, and disturbances of lipid and protein reabsorption from the gut lumen. The appearance of lymphatic edema invokes complex biological alterations. Many of these changes seem to relate uniquely to chronic lymphatic edema, including a profound stimulus to collagen and adipose deposition. Despite the recent advances in our understanding of these disorders, substantial knowledge gaps remain; these gaps inhibit our ability to accurately identify, categorize, treat, and prevent these diseases. Future diagnostic, therapeutic, and reproductive decisions for affected individuals require an accurate knowledge of the clinical and laboratory presentation, mode of inheritance, treatment response, outcomes, and prognosis.     

Comparison of 4D Phase-Contrast MRI Flow Measurements to Computational Fluid Dynamics Simulations of Cerebrospinal Fluid Motion in the Cervical Spine

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes along the cervical SSS in terms of peak CSF velocities in both the cranial and caudal direction and visual interpretation of thru-plane velocity profiles. 4D PC MRI peak CSF velocities were consistently greater than the CFD peak velocities and these differences were more pronounced in CM patients than in healthy subjects. In the upper cervical SSS of CM patients the 4D PC MRI quantified stronger fluid jets than the CFD. Visual interpretation of the 4D PC MRI thru-plane velocity profiles showed greater pulsatile movement of CSF in the anterior SSS in comparison to the posterior and reduction in local CSF velocities near nerve roots. CFD velocity profiles were relatively uniform around the spinal cord for all subjects. This study represents the first comparison of 4D PC MRI measurements to CFD of CSF flow in the cervical SSS. The results highlight the utility of 4D PC MRI for evaluation of complex CSF dynamics and the need for improvement of CFD methodology. Future studies are needed to investigate whether integration of fine anatomical structures and gross motion of the brain and/or spinal cord into the computational model will lead to a better agreement between the two techniques.     

Sustained high-pressure in the spinal subarachnoid space while arterial expansion is low may be linked to syrinx development

Syringomyelia (a spinal cord cyst) usually develops as a result of conditions that cause cerebrospinal fluid (CSF) obstruction. The mechanism of syrinx formation and enlargement remains unclear, though previous studies suggest that the fluid enters via the perivascular spaces (PVS) of the penetrating arteries of the spinal cord, and that alterations in the CSF pulse timing and pressure could contribute to enhanced PVS inflow. This study uses an idealised computational model of the PVS to investigate the factors that influence peri-arterial fluid flow. First, we used three sample patient-specific models to explore whether changes in subarachnoid space (SAS) pressures in individuals with and without syringomyelia could influence PVS inflow. Second we conducted a parametric study to determine how features of the CSF pulse altered perivascular fluid, including alterations to timing and magnitude of the peak SAS pressure, the timing of reversal from high to low pressure (diastolic phase), and the area under the pressure–time curve. The model for the patient with syringomyelia had higher net CSF inflow to the PVS than the two subjects without syringomyelia. In the parametric study, only increasing the area under the high pressure region of the SAS pulse substantially increased PVS inflow, when coupled with a temporal shift in arterial and SAS pulses. This suggests that a period of sustained high SAS pressure while arterial diameter is low may increase net CSF pumping into the PVS.     

Identification of brain cell death associated proteins in human post-mortem cerebrospinal fluid

Following any form of brain insult, proteins are released from damaged tissues into the cerebrospinal fluid (CSF). This body fluid is therefore an ideal sample to use in the search for biomarkers of neurodegenerative disorders and brain damage. In this study, we used human post-mortem CSF as a model of massive brain injury and cell death for the identification of such protein markers. Pooled post-mortem CSF samples were analyzed using a protocol that combined immunoaffinity depletion of abundant CSF proteins, off-gel electrophoresis, SDS-PAGE and protein identification by LC-MS/MS. A total of 299 proteins were identified, of which 172 proteins were not previously described to be present in CSF. Of these 172 proteins, more than 75% have been described as intracellular proteins suggesting that they were released from damaged cells. Immunoblots of a number of proteins were performed on individual post-mortem CSF samples and confirmed elevated concentrations in post-mortem CSF compared to ante-mortem CSF. Interestingly, among the proteins specifically identified in the post-mortem CSF, several have been previously described as biochemical markers of brain damage.     

Thoracic lymphatic disorders

Thoracic complications of lymphatic disorders can culminate in respiratory failure and death and should be considered in any patient with a lymphatic disease and clinical or radiographic evidence of chest disease. Congenital lymphatic disorders are being increasingly recognized in the adult population. The spectrum of thoracic manifestations of lymphatic disorders ranges from incidental radiographic findings to diffuse lymphatic disease with respiratory failure. This article serves to review some recent advances that allow improved diagnosis and management of thoracic lymphatic disorders. Herein, we describe their anatomical and physiologic effects, the time course of their progression, and the therapies that are currently available. The management of malignant (cancerous) lymphatic disorders of the thorax is beyond the scope of this paper.     

Huntington's disease: modeling the gait disorder and proposing novel treatments

Huntington's disease is a movement disorder originated from malfunctioning of Basal Ganglia (BG). There are some models for this disease, most of them being conceptual. So, it seems that considering all physiological information and structural specifications to develop a holistic model is needed. We introduce a computational model based on experimental and physiological findings. Parts of the brain known to be involved in Huntington's disease are all considered in our model and most features of the movement disorders have been appeared in the model. This mathematical model has considered the involved parts of the brain in a fairly accurate way, explaining the behavior and mechanism of the disease according to the physiological information. Our model has several advantages. It is able to simulate the normal and Huntington's disease stride time intervals. It shows how the present treatment, i.e. diazepam, is able to ameliorate the gait disorder. In this research we assessed the effects of changing some neurotransmitter levels in order to propose new treatments. Although we showed that gamma amino butyric acid (GABA) blockers reduce Huntington's disease movement disorder, but we discussed that it is unfair to use this route for treatment. We evaluated our model response to increment of GABA, alone and observed that the gait disorder was strengthened. Our novel idea in this regard is resuscitation of BG loop in order to maintain its major physiological functions, and at the same time raising the threshold in order to weaken the internal disturbances. Our last idea about BG treatment is to decrease glutamate. Our model was able to show the effectiveness of this treatment on Huntington's disease disturbances. We propose that experimental studies should be designed in which these two novel methods of treatment will be evaluated. This validation would implement a milestone in treatment of such a debilitating disease at Huntington.     

The presence of arachnoiditis affects the characteristics of CSF flow in the spinal subarachnoid space: a modelling study

Syringomyelia is a neurological disorder characterised by high pressure fluid-filled cysts within the spinal cord. As syringomyelia is associated with abnormalities of the central nervous system that obstruct cerebrospinal fluid (CSF) flow, it is thought that changes in CSF dynamics play an important role in its pathogenesis. Using three-dimensional computational models of the spinal subarachnoid space (SAS), this study aims to determine SAS obstructions, such as arachnoiditis, change in CSF dynamics in the SAS. The geometry of the SAS was reconstructed from a series of MRI images. CSF is modelled as an incompressible Newtonian fluid with a dynamic viscosity of 1 mPa s. Three computational models simulated CSF flow in either the unobstructed SAS, or with the SAS obstructed by a porous region simulating dorsal or circumferential arachnoiditis. The permeability of this porous obstruction was varied for the model with dorsal arachnoiditis. The results show that arachnoiditis increases flow resistance in the SAS and this is accompanied by a modest increase in magnitude and/or shift in timing (with respect to the cardiac cycle) of the CSF pressure drop across the region of arachnoiditis. This study suggests that syrinx formation may be related to a change in temporal CSF pulse pressure dynamics.     

Histochemical studies on iron absorption in Ophiocephalus punctatus and Heteropneustes fossilis.

Iron absorption in both the teleost fishes Ophiocephalus punctatus and Heteropneustes fossilis, initially starts after 2h of feeding the iron diet. However, at this stage, there is no absorption of iron in the posterior intestine of both the fishes. Absorption initially starts along the brush border of enterocytes of the villi. Later, it gets accumulated in the supranuclear region of the epithelial cells and then through these cells, it is transported into the cores of the villi. The absorbed amount ultimately reaches along the bases of the villi. Through the blood capillaries, which are situated in the submucosa, absorbed iron is passed on to the blood stream. Although, the entire intestine of both the fishes is able to absorb iron but the regional variations have been noted. In contrast to the posterior intestine, the anterior and middle intestine of both the fishes show better iron absorption. The pyloric caeca of Ophiocephalus have comparatively less affinity for iron absorption. However, the intestine of Heteropneustes shows more affinity for iron absorption than the intestine of Ophiocephalus.     

Increased Neural Cell Adhesion Molecule in the CSF of Patients with Mood Disorder

Abstract: Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system. Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble N-CAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder.