Circulating Blood-Brain Barrier Proteins for Differentiating Ischaemic Stroke Patients from Stroke Mimics.

Background: Stroke is one of the leading causes of death and disability worldwide. The diagnosis of stroke remains largely clinical, yet widely used stroke scoring systems and brain imaging do not satisfactorily allow the distinction of ischaemic stroke (IS) patients from stroke mimics (SMs). Blood biomarkers are promising tools that could facilitate clinical triage.

Surface modified hexagonal upconversion nanoparticles for the development of competitive assay for biodetection.

Up-conversion nanoparticles (UCNPs) of sodium yttrium fluoride with ytterbium and erbium ions as sensitizer and activator (β-NaYF/Yb/Er) have been synthesised by a solvothermal method. The synthesised particles were found to be highly uniform in size (~50 nm) and of hexagonal crystal phase producing strong up-conversion luminescence dominated in the green wavelength region. During the synthesis, photoluminescence properties of the reaction mixture were monitored at regular intervals to ensure the required particle size distribution and luminescence efficiency.

A Novel Dynamic Human In Vitro Model for Studying the Blood-Brain Barrier.

Constructing a reliable in vitro blood-brain barrier (BBB) model using human primary cells has been considered a major challenge during the past decades. These systems could provide valuable information regarding the effect of therapeutic compounds on different BBB cell types (endothelial cells, astrocytes, pericytes) and their ability to cross the barrier in order to reach the brain. Several attempts have been made to develop in vitro BBB models, but these studies mainly used rat, bovine, and porcine cells rather than human primary cells.

Current approaches and advances in the imaging of stroke.

A stroke occurs when the blood flow to the brain is suddenly interrupted, depriving brain cells of oxygen and glucose and leading to further cell death. Neuroimaging techniques, such as computed tomography and magnetic resonance imaging, have greatly improved our ability to visualise brain structures and are routinely used to diagnose the affected vascular region of a stroke patient's brain and to inform decisions about clinical care. Currently, these multimodal imaging techniques are the backbone of the clinical management of stroke patients and have immensely improved our ability to visualise brain structures.

Barium yttrium fluoride based upconversion nanoparticles as dual mode image contrast agents.

Dual labeled contrast agents could provide better complementary information for bioimaging than available solely from a single modality. In this paper we investigate the suitability of Yb and Er-doped BaYF upconversion nanoparticles (UCNPs) as both optical and X-ray micro computed tomography (μCT) contrast agents. Stable, aqueous UCNP dispersions were synthesised using a hydrothermal method with the addition of polyethyleneimine (PEI).

Affimer-Based Europium Chelates Allow Sensitive Optical Biosensing in a Range of Human Disease Biomarkers.

The protein biomarker measurement has been well-established using ELISA (enzyme-linked immunosorbent assay), which offers good sensitivity and specificity, but remains slow and expensive. Certain clinical conditions, where rapid measurement or immediate confirmation of a biomarker is paramount for treatment, necessitate more rapid analysis. Biosensors offer the prospect of reagent-less, processing-free measurements at the patient's bedside.

Subchronic hypoxia pretreatment on brain pathophysiology in unilateral common carotid artery occluded albino rats.

Objective: This study was aimed to assess the effect of unilateral common carotid artery occlusion on brain pathophysiology in rats pretreated with subchronic hypoxia.

Materials And Methods: Rats (200 ± 20 g) were randomized into three groups: Group 1 served as sham, Group 2 were normoxic (21% O and 79% N), and Group 3 were hypoxia preconditioned (10% O and 90% N) for 21 days before left common carotid artery occlusion (LCCAO). The LCCAO was done for 75 min followed by reperfusion for 12 h.

Selective cellular imaging with lanthanide-based upconversion nanoparticles.

Upconversion nanoparticles (UCNPs) with sodium yttrium fluoride, NaYF (host lattice) doped with Yb (sensitizer) and Er (activator) were synthesized via hydrothermal route incorporating polyethyleneimine (PEI) for their long-term stability in water. The cationic PEI-modified UCNPs with diameter 20 ± 4 nm showed a zeta potential value of +36.5 mV and showed an intense, visible red luminescence and low-intensity green emission with 976 nm laser excitation.

A novel dynamic multicellular co-culture system for studying individual blood-brain barrier cell types in brain diseases and cytotoxicity testing.

Blood brain barrier (BBB) cells play key roles in the physiology and pathology of the central nervous system (CNS). BBB dysfunction is implicated in many neurodegenerative diseases, including Alzheimer's disease (AD). The BBB consists of capillary endothelial cells, pericytes encircling the endothelium and surrounding astrocytes extending their processes towards it.

Tau pathology and neurochemical changes associated with memory dysfunction in an optimised murine model of global cerebral ischaemia - A potential model for vascular dementia?

Cerebral ischemia is known to be a major cause of death and the later development of Alzheimer's disease and vascular dementia. However, ischemia induced cellular damage that initiates these diseases remain poorly understood. This is primarily due to lack of clinically relevant models that are highly reproducible.

The theoretical molecular weight of NaYF :RE upconversion nanoparticles.

Upconversion nanoparticles (UCNPs) are utilized extensively for biomedical imaging, sensing, and therapeutic applications, yet the molecular weight of UCNPs has not previously been reported. Herein, we present a theory based upon the crystal structure of UCNPs to estimate the molecular weight of UCNPs: enabling insight into UCNP molecular weight for the first time. We estimate the theoretical molecular weight of various UCNPs reported in the literature, predicting that spherical NaYF4 UCNPs ~ 10 nm in diameter will be ~1 MDa (i.

Photoluminescence intensity ratio of Eu-conjugated lactates-A simple optical imaging technique for biomarker analysis for critical diseases.

Instant measurement of elevated biomarkers such as lactic acid offers the most promising approaches for early treatment and prevention of many critical diseases including cardiac arrest, stroke, septic shock, trauma, liver dysfunction, as well as for monitoring lactic acid level during intense exercise. In the present study, a unique dependence of visible photoluminescence of Eu ions resulting from D to F transitions, which can be exploited for rapid detection of biomarkers, both in vitro and ex vivo, has been reported. It is observed that the integrated intensity ratio of photoluminescence signals dominating at 591 and 616 nm originating from D to F and D to F transitions in Eu ions can be used as a biosensing and bioimaging tool for detection of biomarkers released at disease states.

α-tocopherol supplementation prevents lead acetate and hypoxia-induced hepatic dysfunction.

Objective: Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats.

Therapeutic benefits of nanoparticles in stroke.

Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA) is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy, and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy.

Centrally administered CDP-choline induced cardiovascular responses are mediated by activation of the central phospholipase-prostaglandin signaling cascade.

The present study was designed to determine the involvement of central prostaglandin synthesis on the pressor and bradycardic effect of cytidine 5'-diphosphocholine (CDP-choline). Intracerebroventricular (i.c.

Nanotechnology for the detection and therapy of stroke.

Over the years, nanotechnology has greatly developed, moving from careful design strategies and synthesis of novel nanostructures to producing them for specific medical and biological applications. The use of nanotechnology in diagnostics, drug delivery, and tissue engineering holds great promise for the treatment of stroke in the future. Nanoparticles are employed to monitor grafted cells upon implantation, or to enhance the imagery of the tissue, which is coupled with a noninvasive imaging modality such as magnetic resonance imaging, computed axial tomography or positron emission tomography scan.

The effect of centrally injected CDP-choline on respiratory system; involvement of phospholipase to thromboxane signaling pathway.

CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit cardiovascular, neuroendocrine neuroprotective actions. On the other hand, little is known regarding its respiratory actions and/or central mechanism of its respiratory effect.

Protective effect of L-ascorbic acid on nickel induced pulmonary nitrosative stress in male albino rats.

Nickel sulfate stimulates inducible nitric oxide synthase (i-NOS) and increases serum nitric oxide concentration by overproduction of reactive nitrogen species due to nitrosative stress. The present study was undertaken to assess possible protective role of L-ascorbic acid as an antioxidant against nickel induced pulmonary nitrosative stress in male albino rats. We studied the effect of the simultaneous treatment with L-ascorbic acid (50 mg/100 g b.

Changes in glutamate transporter expression in mouse forebrain areas following focal ischemia.

Dysfunction of glutamate transporters has been proposed to promote neuronal death in modelled cerebral ischemia. However, these studies have produced conflicting results and the changes in glutamate transporter expression have not yet been examined in a mouse focal ischemic stroke model. This study used quantitative real-time reverse-transcription polymerase chain reaction to examine glutamate transporter mRNA expression in the hippocampus, cortex and striatum in a mouse model of focal ischemic stroke induced by middle cerebral artery occlusion (MCAO).

L-ascorbic acid and α tocopherol supplementation and antioxidant status in nickel- or lead-exposed rat brain tissue.

We evaluated the effect of L-ascorbic acid and alpha-tocopherol supplementation on plasma and whole brain nitric oxide level and antioxidant status in nickel sulfate- or lead acetate- treated male albino rats. Nitric oxide and lipid peroxide levels in whole brain tissue and plasma increased following nickel and lead treatment but significantly returned to near-normal values upon L-ascorbic acid or alpha-tocopherol supplementation. In brain tissue, antioxidant enzymes--superoxide dismutase, glutathione peroxidase, glutathione peroxidase, and catalase--along with the glutathione level decreased significantly after both treatments but significantly improved upon simultaneous supplementation with L-ascorbic acid or alpha-tocopherol.

Co-localisation of markers for glycinergic and GABAergic neurones in rat nucleus of the solitary tract: implications for co-transmission.

Immunoreactive structures visualised with antibodies to glycine were prominent in areas of the nucleus of the solitary tract (NTS) surrounding the tractus solitarius, but scarcer in medial and ventral areas of the nucleus. This contrasted with a higher density, more homogenous distribution of structures labelled for gamma-aminobutyric acid (GABA). Immunolabelling of adjacent semi-thin sections nonetheless indicated a close correspondence between cells and puncta labelled by glycine and GABA antisera in certain NTS areas.

Differential distribution of 5-HT 1A and 5-HT 1B-like immunoreactivities in rat central nucleus of the amygdala neurones projecting to the caudal dorsomedial medulla oblongata.

Neurones in the central nucleus of the amygdala (CeA) projecting to the caudal dorsomedial medulla oblongata play a key role in the autonomic expression of emotional behaviour. We have earlier shown that these projections from the CeA contain gamma-aminobutyric acid. The CeA receives a dense serotonergic innervation from the raphé nuclei and expresses several serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes, including the 5-HT(1A) and 5-HT(1B) subtypes.

Increased GABA B receptor subtype expression in the nucleus of the solitary tract of the spontaneously hypertensive rat.

Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system was compared between the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms were present as well as B2.

Central nucleus of amygdala projections to rostral ventrolateral medulla neurones activated by decreased blood pressure.

The central nucleus of amygdala (CeA) participates in cardiovascular regulation during emotional behaviour but it has not been established whether any of these effects are mediated through its direct connections to blood pressure-regulating neurones in the rostral ventrolateral medulla (RVLM). The RVLM contains barosensitive neurones that maintain resting blood pressure via their projections to sympathetic preganglionic neurones in the thoracic spinal cord. In this study on rats, we used combined anterograde neuronal tracing of CeA projections with confocal and electron microscopic immunohistochemical detection of phenylethanolamine-N-methyltransferase, the adrenaline-synthesizing enzyme present in C1 catecholamine neurones of the RVLM, and Fos, the protein product of the c-fos proto-oncogene.