Irradiation of the head by60Co opens the blood-brain barrier for drugs in rats

Summary The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a⁶⁰Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of³H₂O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.     

Saturable transport of amphetamine across the blood-brain barrier

Zusammenfassung Untersuchungen über die die Penetration von Amphetaminen ins Gehirn bestimmenden Faktoren. Entwicklung neuer Aspekte im Hinblick auf den Transport von Amphetaminen über die Blut-Hirn-Schranke mittels eines Trägers.

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Supported in part by USPHS Research Grant No. NSO8884, NINDS.     

Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain

The role of nitric oxide (NO), a well known vasodilator, in the regulation of blood-brain barrier (BBB) permeability is not clear. Therefore, the present study was planned to assess the role of NO-releasing compounds like sodium nitroprusside (SNP) and the active metabolite of molsidomine, SIN-1, as well as a precursor of NO, L-arginine, on this physiological barrier. The permeability was assessed by using several tracers. All three agents increased the permeability of BBB to the tracer. The increase in permeability caused by L-arginine was not blocked by N-nitro-L-arginine methyl ester (L-NAME). L-Arginine-treated brains did not show an elevation of nitrite content, thus ruling out the possibility of NO generation and its involvement in BBB permeability alteration. It is concluded that NO itself causes an increase in the permeability of BBB. However arginine-induced opening is not NO mediated.CDRI Communication Number: 5178.     

Immunologic blood-brain barrier in the polyoma virus--Syrian hamster system]

The authors report premilinary results of an experiment on permeability of the blood-brain barrier (BBB) to anti-tumor virus-induced immunological factors in the polyoma virus/Syrian Hamster system. The animals were protected by subcutaneous or intracranial injections with virus before challenge with polyoma virus transformed cells by both routes. BBB seemed to be permeable to the efferent part of the subcutaneously induced immune reaction. On the contrary, antigenic information introduced in the central nervous system was trapped inside the BBB. Thus the BBB might offer a "one-way" permeability in this system.     

Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit

Summary The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.Acknowledgment. This work was supported by grants from the Swiss National Science Foundation (Nos 3.871-72, 3.525.75, 3.443.074, 3.780.076), Fonds für Lehre und Forschung der Universität Basel, Merck Sharp and Dohme (USA), Ciba-Stiftung Basel.     

Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit

The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.     

A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles

Poly(MePEG₂₀₀₀cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.Received 4 March 2005; accepted 14 April 2005     

Labile lipophilic derivatives of norepinephrine capable of crossing the blood-brain barrier

Zusammenfassung Das in vivo leicht hydrolysierbare 0, 0, 0-Triacetat und das zyklische Brenzkatechin-carbonat desl-Noradrenalins setzen im Herzen der Maus tritiiertes Noradrenalin frei. Beide Derivate sowie das 0, 0, 0-Trimethylsilyl-l-noradrenalin-7-³H, sind genügend lipophil, um leicht die Liquorschranke zu überschreiten, wo sie im Zentralnervensystem langsam tritiiertes Noradrenalin freisetzen. Solche Noradrenalin-Depot-Derivate sind möglicherweise von therapeutischem Interesse.     

The effect of nickel chloride on the permeability of the blood-brain barrier

Zusammenfassung Die Permeabilitätsverhältnisse der Blut-Hirn-Schranke nach spezifischer Hemmung der 5-Nucleosid-Phosphatase wurden mittels Fluoreszenzmikroskopie studiert und eine Permeabilitätserhöhung nach Injektion von Nickelchlorid gefunden: Trypanblau kann dabei ins Gehirn penetrieren, was dafür spricht, dass die 5-Nucleosid-Phosphatase bei der Regulation der Kapillarpermeabilität eine bedeutende Rolle spielt.     

The physiological effects of ionic lanthanum on the insect blood-brain barrier

Summary Lanthanum had a small effect on the barrier, but did not significantly increase its sodium or patossium permeability. There was no effect on nerve conduction unless the barrier was deliberately damaged. The results lend confidence to the use of lanthanum as an extracellular tracer.     

High permeability of insect blood-brain barrier to alcohols demonstrated by an electrophysiological technique.

Using the anaesthetic effects of the alcohols to measure their concentration within the cockroach central nervous system, it is shown that the lower homologues have access half-times of only a few seconds. Slower access of the higher homologues is interpreted in terms of a reservoir effect resulting from their higher liposolubility.     

Survival enhanced by skin-wound trauma in mice exposed to60Co radiation

Summary A 4%-body-surface skin wound given 24 h before exposure of mice to⁶⁰Co radiation raised the LD 50/30 from 825 to 975 rads, resulting in a dose reduction factor of 1.2. Enhanced survival of mice wounded before radiation was independent of extramedullary splenic myelocytopoiesis.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under research work unit 8324-60406. The views presented in this paper are those of the authors. No endorsement by the Defense Nuclear Agency has been given or should be inferred.Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Research, National Research Council.     

Aspects of interastrocytic gap junctions in blood-brain barrier in the experimental penumbra area,revealed by transmission electron microscopy and freeze-fracture

Summary Interastrocytic gap junctions in the blood-brain barrier of the experimental penumbra area were studied in the cat caudate nucleus 1 h after ischemia. Transmission electron microscopy and freeze-fracture studies revealed only slight changes in gap junctions between astrocytes, indicating that these junctions are very resistant to hypoxia.Authors are grateful to M. Guerricabeitia and Ch. Bourdier for their technical and secretarial assistance.     

Aspects of interastrocytic gap junctions in blood-brain barrier in the experimental penumbra area, revealed by transmission electron microscopy and freeze-fracture

Interastrocytic gap junctions in the blood-brain barrier of the experimental penumbra area were studied in the cat caudate nucleus 1 h after ischemia. Transmission electron microscopy and freeze-fracture studies revealed only slight changes in gap junctions between astrocytes, indicating that these junctions are very resistant to hypoxia.     

Penetration of oximes across the blood-brain barrier. A histochemical study of the cerebral cholinesterases reactivation

Summary The comparison of the effects of 4 oximes upon the cerebral cholinesterases reactivation after intoxication with paraoxon shows that the best results are obtained with toxogonine and 1574 [(carbaldoxime-4 pyridinium)-1(methyl-1 imidazolium-3)-3 propane]. The reactivation power of this latter compound seems due to the ease with which it can pass through the blood-brain barrier.Supported by grants from the Direction des Recherches et Etudes Techniques (D.R.E.T.) (No. 77–275).     

Penetration of oximes across the blood-brain barrier. A histochemical study of the cerebral cholinesterases reactivation.

The comparison of the effects of 4 oximes upon the cerebral cholinesterases reactivation after intoxication with paraoxon shows that the best results are obtained with toxogonine and 1574 [(carbaldoxime-4 pyridinium)-1(methyl-1 imidazolium-3)-3 propane]. The reactivation power of this latter compound seems due to the ease with which it can pass through the blood-brain barrier.