Cerebrospinal Fluid Research 

About: Cerebrospinal Fluid Research is an academic journal. The journal publishes majorly in the area(s): Hydrocephalus & Spina bifida. It has an ISSN identifier of 1743-8454. It is also open access. Over the lifetime, 295 publications have been published receiving 5554 citations.

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

Abstract: This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces.

Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species

Abstract: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to humans has never been clarified. The purpose of this study was to compare the CSF and nasal lymph associations in human and non-human primates with those observed in other mammalian species. Studies were performed in sheep, pigs, rabbits, rats, mice, monkeys and humans. Immediately after sacrifice (or up to 7 hours after death in humans), yellow Microfil was injected into the CSF compartment. The heads were cut in a sagittal plane. In the seven species examined, Microfil was observed primarily in the subarachnoid space around the olfactory bulbs and cribriform plate. The contrast agent followed the olfactory nerves and entered extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. This is the first direct evidence of the association between the CSF and nasal lymph compartments in humans. The fact that the pattern of Microfil distribution was similar in all species tested, suggested that CSF absorption into nasal lymphatics is a characteristic feature of all mammals including humans. It is tempting to speculate that some disorders of the CSF system (hydrocephalus and idiopathic intracranial hypertension for example) may relate either directly or indirectly to a lymphatic CSF absorption deficit.

Diagnosis of idiopathic normal pressure hydrocephalus is supported by MRI-based scheme: a prospective cohort study

Abstract: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable neurological syndrome in the elderly Although the magnetic resonance imaging (MRI) findings of tight high-convexity and medial subarachnoid spaces and the ventriculo-peritoneal (VP) shunt with programmable valve are reportedly useful for diagnosis and treatment, respectively, their clinical significance remains to be validated We conducted a multicenter prospective study (Study of Idiopathic Normal Pressure Hydrocephalus on Neurological Improvement: SINPHONI) to evaluate the utility of the MRI-based diagnosis for determining the 1-year outcome after VP shunt with the Codman-Hakim programmable valve Twenty-six centers in Japan were involved in this study Patients aged between 60 and 85 years with one or more of symptoms (gait, cognitive, and urinary problems) and MRI evidence of ventriculomegaly and tight high-convexity and medial subarachnoid spaces received VP shunt using the height/weight-based valve pressure-setting scheme The primary endpoint was a favorable outcome (improvement of one level or more on the modified Rankin Scale: mRS) at one year after surgery, and the secondary endpoints included improvement of one point or more on the total score of the iNPH grading scale Shunt responder was defined by more than one level on mRS at any evaluation point in one year The full analysis set included 100 patients A favorable outcome was achieved in 690% and 800% were shunt responders When measured with the iNPH grading scale, the one-year improvement rate was 770%, and response to the surgery at any evaluation point was detected in 890% Serious adverse events were recorded in 15 patients, three of which were events related to surgery or VP shunt Subdural effusion and orthostatic headache were reported as non-serious shunt-related adverse events, which were well controlled with readjustment of pressure The MRI-based diagnostic scheme is highly useful Tight high-convexity and medial subarachnoid spaces, and enlarged Sylvian fissures with ventriculomegaly, defined as disproportionately enlarged subarachnoid-space hydrocephalus (DESH), are worthwhile for the diagnosis of iNPH This study is registered with ClinicalTrialsgov, number NCT00221091

The function and structure of the cerebrospinal fluid outflow system

Abstract: This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and degree of animal maturation. The functional capabilities of the total CSF drainage system are presented, with evidence that the duality of the system is supported by the changes in fluid outflow dynamics in human and sub-human primates in hydrocephalus. The review also reconciles the relative importance and alterations of each of the outflow systems in a variety of clinical pathological conditions.

Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?

Abstract: In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption.