Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage
ConclusionsCompared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 6, 2023 Category: Neuroscience Source Type: research

SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation
AbstractReissner ’s fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CS F-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulatingSspo, an exceptionally large gene of 15,719 nucleotides, with...
Source: Fluids and Barriers of the CNS - December 5, 2023 Category: Neuroscience Source Type: research

A metabolomics study in aqueous humor discloses altered arginine metabolism in Parkinson ’s disease
ConclusionsA combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - December 4, 2023 Category: Neuroscience Source Type: research

Breaking barriers: exploring mechanisms behind opening the blood –brain barrier
AbstractThe blood –brain barrier (BBB) is a selectively permeable membrane that separates the bloodstream from the brain. While useful for protecting neural tissue from harmful substances, brain-related diseases are difficult to treat due to this barrier, as it also limits the efficacy of drug delivery. To address this, promising new approaches for enhancing drug delivery are based on disrupting the BBB using physical means, including optical/photothermal therapy, electrical stimulation, and acoustic/mechanical stimulation. These physical mechanisms can temporarily and locally open the BBB, allowing drugs and other subst...
Source: Fluids and Barriers of the CNS - November 28, 2023 Category: Neuroscience Source Type: research

Microfluidic models of the neurovascular unit: a translational view
AbstractThe vasculature of the brain consists of specialized endothelial cells that form a blood-brain barrier (BBB). This barrier, in conjunction with supporting cell types, forms the neurovascular unit (NVU). The NVU restricts the passage of certain substances from the bloodstream while selectively permitting essential nutrients and molecules to enter the brain. This protective role is crucial for optimal brain function, but presents a significant obstacle in treating neurological conditions, necessitating chemical modifications or advanced drug delivery methods for most drugs to cross the NVU. A deeper understanding of ...
Source: Fluids and Barriers of the CNS - November 27, 2023 Category: Neuroscience Source Type: research

Local perfusion of capillaries reveals disrupted beta-amyloid homeostasis at the blood-brain barrier in Tg2576 murine Alzheimer ’s model
ConclusionsDisrupted TJ integrity, reduced ABCC1 functionality and decreased RAGE binding were identified as BBB alterations in Tg2576 mice, with the latter finding challenging the current concepts. Our results suggest to manage AD by including modulation of TJ proteins and A β-RAGE binding. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 22, 2023 Category: Neuroscience Source Type: research

Protective effects of pyrroloquinoline quinone in brain folate deficiency
ConclusionThese results demonstrate the effects of brain folate deficiency, which may contribute to the neurological deficits commonly seen in disorders of CFD. PQQ may represent a novel treatment strategy for disorders associated with CFD, as it can increase folate uptake, while in parallel reversing many abnormalities that arise with brain folate deficiency. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 20, 2023 Category: Neuroscience Source Type: research

The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial
ConclusionsPressures changed posture-dependently to differing extents. Changes were most pronounced immediately after entering upright posture (P1) and became less prominent over the chair duration (P2-to-P3), suggesting increased physiologic compensation. Dynamic changes in IAP varied across abdominal locations, motivating the abdominal cavity not to be considered as a unified entity, but sub-compartments with individual dynamics. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 9, 2023 Category: Neuroscience Source Type: research

Subcellular trafficking and transcytosis efficacy of different receptor types for therapeutic antibody delivery at the blood ‒brain barrier
AbstractHere, we report an experimental setup to benchmark different receptors for targeted therapeutic antibody delivery at the blood –brain barrier. We used brain capillary endothelial-like cells derived from induced pluripotent stem cells (hiPSC-BECs) as a model system and compared them to colon epithelial Caco-2 cells. This approach helped to identify favourable receptors for transport into the cell layer itself or for direct ing transport for transcytosis across the cell layer. The sorting receptors transferrin receptor and sortilin were shown to be efficient as antibody cargo receptors for intracellular delivery to...
Source: Fluids and Barriers of the CNS - November 6, 2023 Category: Neuroscience Source Type: research

Pathogenic mechanisms and therapeutic implications of extracellular matrix remodelling in cerebral vasospasm
AbstractCerebral vasospasm significantly contributes to poor prognosis and mortality in patients with aneurysmal subarachnoid hemorrhage. Current research indicates that the pathological and physiological mechanisms of cerebral vasospasm may be attributed to the exposure of blood vessels to toxic substances, such as oxyhaemoglobin and inflammation factors. These factors disrupt cerebral vascular homeostasis. Vascular homeostasis is maintained by the extracellular matrix (ECM) and related cell surface receptors, such as integrins, characterised by collagen deposition, collagen crosslinking, and elastin degradation within th...
Source: Fluids and Barriers of the CNS - November 4, 2023 Category: Neuroscience Source Type: research

Neurovascular unit disruption and blood –brain barrier leakage in MCT8 deficiency
ConclusionsThese findings identify for the first time neurovascular alterations in the MCT8-deficient brain, including a disruption of the integrity of the BBB and alterations in the neurovascular unit ultrastructure as a new pathophysiological mechanism for AHDS. These results open a new field for potential therapeutic targets for the neurological symptoms of these patients and unveils magnetic resonance angiography as a new non-invasive in vivo technique for evaluating the progression of the disease. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - November 3, 2023 Category: Neuroscience Source Type: research

A tissue-engineered model of the blood-tumor barrier during metastatic breast cancer
AbstractMetastatic brain cancer has poor prognosis due to challenges in both detection and treatment. One contributor to poor prognosis is the blood –brain barrier (BBB), which severely limits the transport of therapeutic agents to intracranial tumors. During the development of brain metastases from primary breast cancer, the BBB is modified and is termed the ‘blood-tumor barrier’ (BTB). A better understanding of the differences between the BBB and BTB across cancer types and stages may assist in identifying new therapeutic targets. Here, we utilize a tissue-engineered microvessel model with induced pluripotent ste...
Source: Fluids and Barriers of the CNS - November 3, 2023 Category: Neuroscience Source Type: research

Human isogenic cells of the neurovascular unit exert transcriptomic cell type-specific effects on a blood-brain barrier in vitro model of late-onset Alzheimer disease
ConclusionsCell type-dependent transcriptional effects on LOAD BCECs were identified. Our study suggests that different brain cell types of the NVU have unique roles in maintaining barrier integrity that vary under healthy and LOAD conditions.Graphical abstract. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 31, 2023 Category: Neuroscience Source Type: research

Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
DiscussionA higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome. (Source: Fluids and Barriers of the CNS)
Source: Fluids and Barriers of the CNS - October 25, 2023 Category: Neuroscience Source Type: research

Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity
AbstractThe brain is a highly metabolically active organ requiring a large amount of glucose. Methylglyoxal (MGO), a by-product of glucose metabolism, is known to be involved in microvascular dysfunction and is associated with reduced cognitive function. Maintenance of the blood-brain barrier (BBB) is essential to maintain optimal brain function and a large amount of evidence indicates negative effects of MGO on BBB integrity. In this review, we summarized the current literature on the effect of MGO on the different cell types forming the BBB. BBB damage by MGO most likely occurs in brain endothelial cells and mural cells,...
Source: Fluids and Barriers of the CNS - October 24, 2023 Category: Neuroscience Source Type: research