Search results for "BLOOD-BRAIN BARRIER"
showing 10 items of 141 documents
Innovative in Vitro Method To Predict Rate and Extent of Drug Delivery to the Brain across the Blood–Brain Barrier
2013
The relevant parameters for predicting rate and extent of access across the blood-brain barrier (BBB) are fu,plasma (unbound fraction in plasma), Vu,brain (distribution volume in brain) and Kp,uu,brain (ratio of free concentrations in plasma and brain). Their estimation still requires animal studies and in vitro low throughput experiments which make difficult the screening of new CNS candidates. The aim of the present work was to develop a new whole in vitro high throughput method to predict drug rate and extent of access across the BBB. The system permits estimation of fu,plasma, Vu,brain and Kp,uu,brain in a single experimental system, using in vitro cell monolayers in different condition…
Neuroprotection by erythropoietin administration after experimental traumatic brain injury.
2007
A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and bl…
Small rises in plasma choline reverse the negative arteriovenous difference of brain choline.
1990
The concentrations of free choline in blood plasma from a peripheral artery and from the transverse sinus, in the CSF, and in total brain homogenate, have been measured in untreated rats and in rats after acute intraperitoneal administration of choline chloride. In untreated rats, the arteriovenous difference of brain choline was related to the arterial choline level. At low arterial blood levels (less than 10 microM) as observed under fasting conditions, the arteriovenous difference was negative (about -2 microM), indicating a net release of choline from the brain of about 1.6 nmol/g/min. In rats with spontaneously high arterial blood levels (greater than 15 microM), the arteriovenous diff…
Uptake and storage of choline by rat brain: influence of dietary choline supplementation.
1991
In order to elucidate the regulation of the levels of free choline in the brain, we investigated the influence of chronic and acute choline administration on choline levels in blood, CSF, and brain of the rat and on net movements of choline into and out of the brain as calculated from the arteriovenous differences of choline across the brain. Dietary choline supplementation led to an increase in plasma choline levels of 50% and to an increase in the net release of choline from the brain as compared to a matched group of animals which were kept on a standard diet and exhibited identical arterial plasma levels. Moreover, the choline concentration in the CSF and brain tissue was doubled. In th…
Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats
2009
The influence of diabetes on brain glutamate (GLU) uptake was studied in insulinopenic (streptozotocin [STZ]) and insulin-resistant (diet-induced obesity [DIO]) rat models of diabetes. In the STZ study, adult male Sprague-Dawley rats were treated with STZ (65 mg/kg intravenously) or vehicle and studied 3 weeks later. The STZ rats had elevated plasma levels of glucose, ketone bodies, and branched-chain amino acids; brain uptake of GLU was very low in both STZ and control rats, examined under conditions of normal and greatly elevated (by intravenous infusion) plasma GLU concentrations. In the DIO study, rats ingested a palatable, high-energy diet for 2 weeks and were then divided into weight …
NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhag…
2007
Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectropho…
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis.
2005
G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neurona…
Blood-brain barrier disruption by low-frequency ultrasound.
2006
Background and Purpose— A recent study showed a dramatic increase in cerebral hemorrhage comprising atypical locations with low-frequency ultrasound–mediated recombinant tissue plasminogen activator–thrombolysis in humans. Here, we provide a possible explanation for this phenomenon by a side effect observed in a study using the similar ultrasound device. Methods— The study was originally undertaken to investigate by transcranial Doppler sonography, positron emission tomography and perfusion MRI whether transcranial application of wide-field low-frequency ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral small vessel disease. Results— Showing no clear positive ef…
TOPS-MODE approach for the prediction of blood-brain barrier permeation.
2004
The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentration ratio. The final model explained the 70% of the variance and it was validated through the use of an external validation set (33 compounds of the 119, MAE = 0.33), a leave-one-out crossvalidation (q(2) = 0.65, S(press) = 0.43), fivefold full crossvalidation (removing 28 compounds in each cycle, MAE = 33, RMSE = 0.43) and the prediction of +/- values for an external test set …
Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and m…
2019
Abstract Over the latest years phytochemical consumption has been associated to a decreased risk of both the onset and the development of a number of pathological conditions. In this context indicaxanthin, a betalain pigment from Opuntia ficus-indica fruit, has been the object of sound research. Explored, at first, for its mere antioxidant potential, Indicaxanthin is now regarded as a redox-active compound able to exert significant poly-pharmacological effects against several targets in a number of experimental conditions both in vivo and in vitro. This paper aims to provide an overview on the therapeutical effects of indicaxanthin, ranging from the anti-inflammatory to the neuro-modulatory…