Experimental approaches for manipulating choroid plexus epithelial cells
AbstractChoroid plexus (ChP) epithelial cells are crucial for the function of the blood-cerebrospinal fluid barrier (BCSFB) in the developing and mature brain. The ChP is considered the primary source and regulator of CSF, secreting many important factors that nourish the brain. It also performs CSF clearance functions including removing Amyloid beta and potassium. As such, the ChP is a promising target for gene and drug therapy for neurodevelopmental and neurological disorders in the central nervous system (CNS). This review describes the current successful and emerging experimental approaches for targeting ChP epithelial...
Source: Fluids and Barriers of the CNS - May 26, 2022 Category: Neuroscience Source Type: research

White matter changes should not exclude patients with idiopathic normal pressure hydrocephalus from shunt surgery
ConclusionsAn association between outcome after shunt surgery and volume of PVH was seen, but there was no difference between shunt responders and non-responders in the volumes of DWMH and PVH. We conclude that preoperative assessment of WMC should not be used to exclude patients with iNPH from shunt surgery. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - May 23, 2022 Category: Neuroscience Source Type: research

Arterial vasodilation drives convective fluid flow in the brain: a poroelastic model
AbstractThe movement of fluid into, through, and out of the brain plays an important role in clearing metabolic waste. However, there is controversy regarding the mechanisms driving fluid movement in the fluid-filled paravascular spaces (PVS), and whether the movement of metabolic waste in the brain extracellular space (ECS) is primarily driven by diffusion or convection. The dilation of penetrating arterioles in the brain in response to increases in neural activity (neurovascular coupling) is an attractive candidate for driving fluid circulation, as it drives deformation of the brain tissue and of the PVS around arteries,...
Source: Fluids and Barriers of the CNS - May 15, 2022 Category: Neuroscience Source Type: research

Effects of acute and chronic oxidative stress on the blood –brain barrier in 2D and 3D in vitro models
AbstractOxidative stress is a shared pathology of neurodegenerative disease and brain injuries, and is derived from perturbations to normal cell processes by aging or environmental factors such as UV exposure and air pollution. As oxidative cues are often present in systemic circulation, the blood –brain barrier (BBB) plays a key role in mediating the effect of these cues on brain dysfunction. Therefore, oxidative damage and disruption of the BBB is an emergent focus of neurodegenerative disease etiology and progression. We assessed barrier dysfunction in response to chronic and acute oxida tive stress in 2D and 3D in vi...
Source: Fluids and Barriers of the CNS - May 12, 2022 Category: Neuroscience Source Type: research

Diagnostic biomarker kinetics: how brain-derived biomarkers distribute through the human body, and how this affects their diagnostic significance: the case of S100B
AbstractBlood biomarkers of neurological diseases are often employed to rule out or confirm the presence of significant intracranial or cerebrovascular pathology or for the differential diagnosis of conditions with similar presentations (e.g., hemorrhagic vs. embolic stroke). More widespread utilization of biomarkers related to brain health is hampered by our incomplete understanding of the kinetic properties, release patterns, and excretion of molecules derived from the brain. This is, in particular, true for S100B, an astrocyte-derived protein released across the blood –brain barrier (BBB). We developed an open-source ...
Source: Fluids and Barriers of the CNS - May 11, 2022 Category: Neuroscience Source Type: research

A novel chronic dural port platform for continuous collection of cerebrospinal fluid and intrathecal drug delivery in free-moving mice
ConclusionsThe CDP method enables the collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - May 3, 2022 Category: Neuroscience Source Type: research

Theoretical analysis of wake/sleep changes in brain solute transport suggests a flow of interstitial fluid
AbstractClearance of protein waste products from the brain is accomplished by a combination of advection and diffusion in cerebrospinal fluid (CSF) and interstitial fluid (ISF). In the glymphatic model, there is a flow of ISF in the interstitial space, and both advection and diffusion occur there. Such a flow of ISF would be slow and difficult to detect directly, and its existence has proved controversial. Waste clearance has been shown to occur mainly during sleep, during which the volume of the interstitial space increases substantially due to ISF emitted from astrocytes. Here I show that this volume increase of the inte...
Source: Fluids and Barriers of the CNS - April 13, 2022 Category: Neuroscience Source Type: research

The blood –brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments
AbstractThe response of the blood –brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individ ual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has l...
Source: Fluids and Barriers of the CNS - April 11, 2022 Category: Neuroscience Source Type: research

Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review
AbstractIntraventricular hemorrhage (IVH) is a significant cause of morbidity and mortality in both neonatal and adult populations. IVH not only causes immediate damage to surrounding structures by way of mass effect and elevated intracranial pressure; the subsequent inflammation causes additional brain injury and edema. Of those neonates who experience severe IVH, 25 –30% will go on to develop post-hemorrhagic hydrocephalus (PHH). PHH places neonates and adults at risk for white matter injury, seizures, and death. Unfortunately, the molecular determinants of PHH are not well understood. Within the past decade an emphasi...
Source: Fluids and Barriers of the CNS - April 1, 2022 Category: Neuroscience Source Type: research

Non-coding RNAs in the regulation of blood –brain barrier functions in central nervous system disorders
AbstractThe blood –brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of t he diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases. Cumulative evi dences hav...
Source: Fluids and Barriers of the CNS - March 26, 2022 Category: Neuroscience Source Type: research

Cerebrospinal fluid production by the choroid plexus: a century of barrier research revisited
AbstractCerebrospinal fluid (CSF) envelops the brain and fills the central ventricles. This fluid is continuously replenished by net fluid extraction from the vasculature by the secretory action of the choroid plexus epithelium residing in each of the four ventricles. We have known about these processes for more than a century, and yet the molecular mechanisms supporting this fluid secretion remain unresolved. The choroid plexus epithelium secretes its fluid in the absence of a trans-epithelial osmotic gradient, and, in addition, has an inherent ability to secrete CSF against an osmotic gradient. This paradoxical feature i...
Source: Fluids and Barriers of the CNS - March 22, 2022 Category: Neuroscience Source Type: research

Exploring ITM2A as a new potential target for brain delivery
ConclusionsThe present work describes our efforts to explore the potential of ITM2A as a target mediating transcytosis through the BBB, and highlights the multiple challenges linked to the identification of new brain delivery targets. Our data provide evidence that antibodies against ITM2A are internalized in ITM2A-overexpressing HEK293 cells, and that ITM2A is expressed in brain microvessels, but further investigations will be needed to demonstrate that ITM2A is a potential target for brain delivery. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 21, 2022 Category: Neuroscience Source Type: research

Parasagittal dural space and cerebrospinal fluid (CSF) flow across the lifespan in healthy adults
ConclusionsFindings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 21, 2022 Category: Neuroscience Source Type: research

Expression and functions of adenylyl cyclases in the CNS
AbstractAdenylyl cyclases (ADCYs), by generating second messenger cAMP, play important roles in various cellular processes. Their expression, regulation and functions in the CNS, however, remain largely unknown. In this review, we first introduce the classification and structure of ADCYs, followed by a discussion of the regulation of mammalian ADCYs (ADCY1-10). Next, the expression and function of each mammalian ADCY isoform are summarized in a region/cell-specific manner. Furthermore, the effects of GPCR-ADCY signaling on blood –brain barrier (BBB) integrity are reviewed. Last, current challenges and future directions a...
Source: Fluids and Barriers of the CNS - March 20, 2022 Category: Neuroscience Source Type: research

Dual effect of TAT functionalized DHAH lipid nanoparticles with neurotrophic factors in human BBB and microglia cultures
ConclusionsOverall, this work shows that the TAT-functionalized DHAH-NLCs can cross the BBB, modulate immune responses, and serve as cargo carriers for growth factors; thus, constituting an attractive and promising novel drug delivery approach for the transport of therapeutics through the BBB into the brain. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - March 17, 2022 Category: Neuroscience Source Type: research