1. We have studied the permeability of blood-brain barriers to small molecules such as [(14)C]sucrose, [(3)H]inulin, [(14)C]L-glucose and [(3)H]glycerol from early stages of development (postnatal day 6, P6) in South American opossums (Monodelphis domestica), using a litter-based method for estimating steady-state cerebrospinal fluid (CSF)/plasma and brain/plasma ratios of markers that ...

The central nervous system requires an effective autoregulation of cerebral circulation in order to meet the critical and unusual demands of the brain. In addition, cerebral microvessels has a unique feature, the formation of the blood-brain barrier, which contributes to the stability of the brain parenchymal microenvironment. Many factors are ...

Reelin is a secreted extracellular matrix protein approximately 410 kDa mol. wt that is reduced in brains of patients with schizophrenia, autism, bipolar disorder and major depression. Recent reports also indicate its near absence in sera of some patients with an autosomal recessive form of lissencephaly. Moreover, Reelin is involved ...

Inhaled chemical toxicants can damage the lungs during two phases: (1) the first-pass phase, in which toxicants are initially absorbed through the air/blood barrier, or (2) the circulation-transport phase, in which toxicants are transported back through the lungs with the circulating blood. While respiratory-tract dosimetry for inhaled toxicants is relatively ...

Different clinical outcomes in spite of comparable dietary controls are well known in patients with phenylketonuria. Currently, reasons for this phenomenon are unknown. Kinetic investigations in 15 patients with classic phenylketonuria were performed using in vivo nuclear magnetic resonance spectroscopy before and after an oral phenylalanine load (100 mg/kg body ...

The blood-brain barrier (BBB) is a complex structure of endothelial cells, astroglia, pericytes, and perivascular macrophages enclosed by basal lamina. The BBB regulates the entry of blood-borne molecules and cells into the brain, but it is disrupted in various inflammatory conditions of the central nervous system (CNS). We previously showed ...

Osmotic disruption is currently being used to circumvent the blood-brain barrier (BBB) and enhance the delivery of therapeutic molecules in human brains. To date, however, the time course during the early phase of disruption has not been clarified. In order to demonstrate the rapid change in cerebrovascular permeability after BBB ...

Traditionally, scientists and clinicians have explored peripheral physiological responses to acute hypoxia to explain the pathophysiological processes that lead to acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). After more than 100 years of investigation, little is yet known about the fundamental causes of the headache and nausea that ...

The permeability of albumin, insulin, and human A beta 1--40 at the blood-brain barrier (BBB) was determined in the normal adult mouse (B6/SJL) and in the double transgenic Alzheimer mouse (APP, PS1) by using an I.V. bolus injection technique to quantify the permeability coefficient-surface area (PS) product for each protein ...

This unit describes various protocols for the in vivo quantitation of drug permeability across the rodent blood - brain barrier. Methods for the measurement of drug influx or efflux are described, and support protocols are provided for determining intravascular capillary volume and cerebral perfusion flow. An in situ perfusion technique ...

Opiate-modulating tetrapeptides such as tyrosine-melanocyte-stimulating hormone-release inhibiting factor-1 (Tyr-MIF-1; Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) are saturably transported from brain to blood. We examined whether two recently described endogenous opiate tetrapeptides with similar structures, the mu-specific endomorphins, also are transported across the blood-brain barrier (BBB). We found that the efflux rates of ...

The Gulf war syndrome has drawn increased attention in the issue of the effect of stress on the blood-brain barrier (BBB). We have applied various stressful modalities and tested BBB disruption as measured by the amount of Evans blue (EB) retained by brain parenchyma. We have evaluated the retention of ...

A 7-year-old boy was playfully revolving a partly insulated electric wire which accidentally struck a bamboo pole in its path. He soon found that his left nostril was hit and blood trickled from the site. Unsuspected on investigation, a small fragment of the wire was found within the brain. The ...

Osmotic disruption of the blood-brain barrier (BBB) by mannitol is currently being used to enhance drug delivery in human brains. Despite clinical and experimental interest, to date the time course in the early phase of disruption has not been accurately identified. The mechanism in barrier closure also remains elusive. We ...

Reactive barriers are passive and in situ ground water treatment systems. Heterogeneities in hydraulic conductivity (K) within the aquifer-reactive barrier system will result in higher flux rates, and reduced residence times, through portions of the barrier. These spatial variations in residence time will affect the treatment capacity of the barrier. ...

Two major types of brain edema may be discriminated, characterized by intra- or extracellular fluid accumulation. Intracellular (cytotoxic) edema is found after cerebral ischemia, trauma, intoxications, and metabolic disorders. Pathogenetic mechanisms include (1) failure of active Na+ export via Na/K-ATPase because of energy shortage, (2) increased Na+-permeability, or (3) activation ...

AIM: To study the passive and active transport of fluorescein across the blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63 microm, hyperpigmentation and/or hypopigmentation in patients above 50 years of age). METHODS: 15 patients and 10 healthy subjects were included. Morphological changes were graded from 30 ...

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. ...

Enzyme immunoassay showed penetration of two glia-specific antigens, glial fibrillar acid protein GFAP and specific brain glycoprotein alpha(2)GP, through the blood-brain barrier in rats treated with toxic doses of sodium barbital. The permeability of the blood-brain barrier was completely normalized 3 days after treatment. This method can be used in ...

PYR, a reversible AChE inhibitor, is the current pretreatment against OP intoxication. However, PHY in the presence or absence of SCO on one side, and HUP on the other side, could be considered as potential substitutes for PYR. In the present study, the effects of the subchronic administration of these ...

Adenosine is an inhibitory neuromodulator in the central nervous system and has been reported to have neuroprotective properties. Using a dynamic in vitro blood-brain barrier, we investigated the hypothesis that inhibition of adenosine transporters on the lumenal side of the blood-brain barrier may decrease the loss of adenosine from the ...

Chemokines are a large family of small, inducible, secreted, chemoattractant cytokines that are involved in inflammatory processes. It is well known that systemic and CNS infections cause disruption of the blood-brain barrier (BBB); however, it is not clear how chemokines are involved in this process. We studied the pharmacokinetics of ...

The blood-brain barrier minimizes the entry of molecules into brain tissue. This restriction arises by the presence of tight junctions (zonulae occludens) between adjacent endothelial cells and a relative paucity of pinocytotic vesicles within endothelium of cerebral arterioles, capillaries, and venules. Many types of stimuli can alter the permeability characteristics ...

The blood-brain barrier (BBB) is comprised of the endothelial cells that line the capillaries of the brain. The unique characteristics of this barrier include tight intercellular junctions, a complex glycocalyx, a paucity of pinocytic vesicles, and an absence of fenestra. These properties allow for the selective exchange of substances between ...

Since the central nervous acting agent, tetramethylpyrazine, is reported to have appreciable blood-brain barrier penetrability, a design allowing simultaneous and continual monitoring of drug concentrations in blood and brain was employed to study the distribution of intravenously administered tetramethylpyrazine (10 mg kg(-1)). The system consisted of two microdialysis probes, each ...

Leptin is secreted by adipose tissue and thought to regulate appetite at the central level. Several studies have explored the central nervous system (CNS) entry of this peptide across the blood-brain and blood-cerebrospinal fluid (CSF) barriers in parallel, but this is the first to explore the transport kinetics of leptin ...

The Earth's convecting upper mantle can be viewed as comprising three main reservoirs, beneath the Pacific, Atlantic and Indian oceans. Because of the uneven global distribution and migration of ridges and subduction zones, the surface area of the Pacific reservoir is at present contracting at about 0.6 km2 x y(r-1), ...

A new class of drugs, borylated derivatives of ferrocenium compounds, which show a comparatively facile synthesis is investigated on their boron neutron capture accumulation. Investigations focused on the fast and effective testing of 12 ferrocene derivatives with tetracoordinated boron atoms, which should accumulate in rodent tumors. The macroscopic studies on ...

Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was produced by subcutaneous injection of formalin, lambda-carrageenan, or complete Freund's adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity ...

PET neuroimaging of serotonin responsivity relied previously mainly on fenfluramine, but that drug has been withdrawn from the market. Therefore, we determined whether clomipramine, which stimulates serotonergic mechanisms by inhibiting serotonin reuptake, has reliable effects in the healthy human brain as measured by [15O]H2O PET. The clomipramine challenge markedly reduced ...

Penetration of the blood-brain barrier or blood-cerebrospinal fluid barrier is necessary if a drug is to achieve the required concentration for a desired pharmacological effect. Efflux transport systems at such barriers provide protection for the CNS by removing drugs from the brain or cerebrospinal fluid, and transferring them to the ...

Pathological states (i.e. stroke, cardiac arrest) can lead to reduced blood flow to the brain potentially altering blood-brain barrier (BBB) permeability and regulatory transport functions. BBB disruption leads to increased cerebrovascular permeability, an important factor in the development of ischemic brain injury and edema formation. In this study, reduced flow ...

Bibliography: leaves 318-367.

The purpose of this study was to examine the relationship between Czosnyka and others' Pressure Reactivity Index (PRx) and neurologic outcome in patients with acute brain injury, including traumatic brain injury (TBI) and cerebrovascular pathology. PRx measures the correlation between arterial blood pressure and intracranial pressure waves and may reflect ...

The effect of electroacupuncture (EA) on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion (I-R) was investigated in rats. The dye Evans Blue (EB) was used as a tracer for assessing the disruption of BBB. Fluorescence quantification of EB was performed to explore the temporal pattern of permeability of BBB after ...

The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood-cerebrospinal fluid ...

This study was undertaken to investigate the dynamics of blood-brain barrier breakdown in an in vivo rat model of selective CNS vulnerability. 1,3-Dinitrobenzene was used to induce rapid glial degeneration in highly defined areas of the brainstem. Leakage of fluorescent dextran was used to demonstrate the breakdown of the blood-brain ...

There are several transport systems for peptides and polypeptides at the blood-brain barrier (BBB) which facilitate the passage of bioactive substances from blood to brain or from brain to blood. Nonetheless, it would be a novel concept for one peptide or polypeptide to activate the transport of another peptide with ...

The objective of this study was to investigate the impact of probenecid on the blood-brain barrier (BBB) transport of morphine-3-glucuronide (M3G). Two groups of rats received an exponential infusion of M3G over 4 h to reach a target plasma concentration of 65 microM on two consecutive days. Probenecid was co-administered ...

OBJECTIVE: To estimate the frequency of, and assess risk factors for, percutaneous, mucous membrane, and cutaneous blood contacts sustained by healthcare workers (HCWs) during the delivery of infusion therapy and the performance of procedures involving sharp instruments in the home setting. DESIGN: Prospective surveillance of percutaneous, mucous membrane, and cutaneous ...

(S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H-quinoxaline-carboxylic acid isopropylester (GW420867X) inhibits HIV-1 reverse transcriptase and could be used for the treatment of HIV infection. This study quantified the movement of [14C]GW420867X into the CNS by means of a guinea-pig brain perfusion technique. Results indicated that [14C]GW420867X can enter the brain (Kin: 38.4+/-7.7 microl min(-1) g(-1)) ...

The cytokine interleukin-1beta (IL-1beta) is implicated in a broad spectrum of CNS pathologies, in which it is thought to exacerbate neuronal loss. Here, the effects of injecting recombinant rat IL-1beta into the striatum of 3-week-old rats were followed noninvasively from 2 to 123 hr using magnetic resonance imaging and spectroscopy. ...

Agouti-related protein (AgRP), expressed in both the periphery and the brain, can result in obesity. Its active C-terminal fragment, AgRP(83-132), was recently reported to increase feeding and antagonize alpha-melanocyte-stimulating hormone (alpha-MSH) and leptin. We used multiple-time regression analysis to show that the rate at which AgRP(83-132) crossed the blood-brain barrier ...

We have investigated the transport characteristics of dehydroepiandrosterone sulfate (DHEAS), a neuroactive steroid, at the blood-brain barrier (BBB) in a series of functional in vivo and in vitro studies. The apparent BBB efflux rate constant of [(3)H]DHEAS evaluated by the brain efflux index method was 2.68 x 10(-2) min(-1). DHEAS ...

P-glycoprotein and multidrug resistance-associated protein transporters in the blood-brain barrier: another important brick in the wall

Cisplatin and gentamicin are two ototoxicants that are supposed to be transported by the paracellar route, i.e. via cellular junctions, to the perilymphatic compartment. This study was initiated to test the hypothesis that susceptive variation of individuals to ototoxic drugs may be explained by variability in transport properties. The transport ...

In vivo nuclear magnetic resonance spectroscopy permits the non-invasive examination of metabolic characteristics of the human brain in a clinical environment. Methods to detect elevated phenylalanine (Phe) in patients with phenylketonuria (PKU) using difference spectroscopy and to estimate absolute brain Phe concentrations, [Phe]brain, have been developed. In patients with classical ...

Optison is a new echocardiographic contrast agent, designed for IV injection, that is very useful in delineating cardiac structures during ultrasound examination. Because Optison could be a valuable adjunct in the diagnosis and evaluation of congenital heart disease, this study was undertaken to assess its effects on the blood-brain barrier ...

Structural and functional abnormalities of the vascular microenvironment determine pathophysiological characteristics of gliomas, such as loss of blood-brain barrier function, tumor cell invasiveness, or permselectivity for large molecules. Moreover, the effectiveness of various therapeutic strategies critically depends upon the successful transvascular delivery of molecules. In order to shed more light ...

PURPOSE: To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. METHODS: Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by ...