Development of hydrocephalus and classical hypothesis of cerebrospinal fluid hydrodynamics: facts and illusions

According to the classical hypothesis of the cerebrospinal fluid (CSF) hydrodynamics, CSF is produced inside the brain ventricles, than it circulates like a slow river toward the cortical subarachnoid space, and finally it is absorbed into the venous sinuses. Some pathological conditions, primarily hydrocephalus, have also been interpreted based on this hypothesis. The development of hydrocephalus is explained as an imbalance between CSF formation and absorption, where more CSF is formed than is absorbed, which results in an abnormal increase in the CSF volume inside the cranial CSF spaces. It is believed that the reason for the imbalance is the obstruction of the CSF pathways between the site of CSF formation and the site of its absorption, which diminishes or prevents CSF outflow from the cranium. In spite of the general acceptance of the classical hypothesis, there are a considerable number of experimental results that do not support such a hypothesis and the generally accepted pathophysiology of hydrocephalus. A recently proposed new working hypothesis suggests that osmotic and hydrostatic forces at the central nervous system microvessels are crucial for the regulation of interstial fluid and CSF volume which constitute a functional unit. Based on that hypothesis, the generally accepted mechanisms of hydrocephalus development are not plausible. Therefore, the recent understanding of the correlation between CSF physiology and the development of hydrocephalus has been thoroughly presented, analyzed and evaluated, and new insights into hydrocephalus etiopathology have been proposed, which are in accordance with the experimental data and the new working hypothesis

The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations

The first scientific and experimental approaches to the study of cerebrospinal fluid (CSF) formation began almost a hundred years ago. Despite researchers being interested for so long, some aspects of CSF formation are still insufficiently understood. Today it is generally believed that CSF formation is an active energy consuming metabolic process which occurs mainly in brain ventricles, in choroid plexuses. CSF formation, together with CSF absorption and circulation, represents the so-called classic hypothesis of CSF hydrodynamics. In spite of the general acceptance of this hypothesis, there is a considerable series of experimental results that do not support the idea of the active nature of CSF formation and the idea that choroid plexuses inside the brain ventricles are the main places of formation. The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far. And finally, to try to offer a physiological explanation by which these contradictions could be avoided. We therefore analyzed the main methods that study CSF formation, which enabled such an understanding, and presented their shortcomings, which could also be a reason for the erroneous interpretation of the obtained results. A recent method of direct aqueductal determination of CSF formation is shown in more detail. On the one hand, it provides the possibility of direct insight into CSF formation, and on the other, it clearly indicates that there is no net CSF formation inside the brain ventricles. These results are contradictory to the classic hypothesis and, together with other mentioned contradictory results, strongly support a recently proposed new working hypothesis on the hydrodynamics of CSF. According to this new working hypothesis, CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The CSF exchange between the entire CSF system and the surrounding tissue depends on (patho)physiological conditions that predominate within those compartments

Quantitative analysis of cerebrospinal fluid flow in complex regions by using phase contrast magnetic resonance imaging

To develop a method for segmenting cerebrospinal fluid (CSF) regions with complex, inhomogeneous pulsatile patterns in phase contrast magnetic resonance imaging (PC-MRI) sequences. Our approach used various temporal features of flow behavior as input attributes in an unsupervised k-means classification algorithm. CSF flow parameters for the cervical subarachnoid spaces and the pontine cistern were calculated in 26 healthy volunteers. Background and aliasing corrections were applied automatically. The algorithm's reproducibility was determined by calculating two parameters (area and stroke volume) while varying the initially selected seed point. The influence of background correction on these parameters was also assessed. The method was highly reproducible, with coefficients of variation of 3 and 4% for the cervical stroke volume and area, respectively. In an analysis of variance, background correction did not have a statistically significant effect on either the stroke volume (p = 0.32) or the CSF net mean flow (p = 0.69) at the C2C3 level. The method presented here enables rapid, reproducible, quantitative analysis of CSF flow in complex regions such as the C2C3 subarachnoid spaces and the pontine cistern. © 2011 Wiley Periodicals, Inc.Grant sponsor: Generalitat Valenciana; Grant number: CTBPRB/2004/342 FPI.Florez, N.; Bouzerar, R.; Moratal Pérez, D.; Meyer, M.; Marti Bonmati, L.; Baledent, O. (2011). Quantitative analysis of cerebrospinal fluid flow in complex regions by using phase contrast magnetic resonance imaging. International Journal of Imaging Systems and Technology. 21(3):290-297. https://doi.org/10.1002/ima.20294S29029721

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca(2+)], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS