Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration

The dorsal raphe nucleus (DRN) and surrounding midbrain of 74 cats were stimulated both electrically and chemically, and carotid flows were measured with electromagnetic flow probes. Stimulation of the DRN caused a frequency-dependent decrease in common carotid vascular resistance, which was abolished by bilateral section of the facial nerve intracranially. Injection of DL-homocysteic acid into the DRN reproduced the effect of electrical stimulation, indicating that the responses arose from excitation of cell bodies within the DRN, not from fibers of passage. The responses were mediated entirely within the brain stem since they remained intact after high spinal cord section. The vasodilator response was blocked by the intravenous administration of the nicotinic ganglion blocker hexamethonium but not by the alpha-adrenoceptor blocker phentolamine. The responses were unaffected by intravenous administration of methysergide but were markedly reduced after depletion of central serotonin by pretreatment with the serotonin depletor, p-chlorophenylalanine. A poststimulus constrictor response was mediated by release of catecholamines from the adrenal medulla and was blocked by the alpha-adrenoceptor antagonist phentolamine. No response involved supracollicular mechanisms since they persisted after decerebration.

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STUDIES IN THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION

Journal of Experimental Medicine ◽

10.1084/jem.111.2.145 ◽

1960 ◽

Vol 111 (2) ◽

pp. 145-153 ◽

Cited By ~ 22

Author(s):

Abraham Penner ◽

Alice Ida Bernheim

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Intravenous Administration ◽

Shiga Toxin ◽

Third Ventricle ◽

Dosage Level ◽

Ventricular System ◽

The Third ◽

The Central Nervous System ◽

The Brain

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion.

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The Distribution of Morphine in the Brain in Fatal Cases Due to the Intravenous Administration of Heroin

Journal of Analytical Toxicology ◽

10.1093/jat/2.2.62 ◽

1978 ◽

Vol 2 (2) ◽

pp. 62-67 ◽

Cited By ~ 19

Author(s):

V.R. Spiehler ◽

R.H. Cravey ◽

R.G. Richards ◽

H.W. Elliott

Keyword(s):

Intravenous Administration ◽

The Brain

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The penetration of 5-oxo-Pro-Arg-Pro into the brain and the major metabolic pathways of this peptide in the rat brain and blood at the intranasal and intravenous administration

Doklady Biochemistry and Biophysics ◽

10.1134/s1607672917020168 ◽

2017 ◽

Vol 473 (1) ◽

pp. 151-154

Author(s):

K. V. Shevchenko ◽

I. Yu. Nagaev ◽

V. P. Shevchenko ◽

L. A. Andreeva ◽

S. I. Shram ◽

...

Keyword(s):

Rat Brain ◽

Intravenous Administration ◽

Metabolic Pathways ◽

The Brain

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Functional activity of p-glycoprotein in blood-brain barrier during experimental par-kinson's syndrome

I P Pavlov Russian Medical Biological Herald ◽

10.23888/pavlovj2019272150-159 ◽

2019 ◽

Vol 27 (2) ◽

pp. 150-159

Author(s):

Ivan V. Chernykh ◽

Aleksey V. Shchulkin ◽

Pavel Yu. Mylnikov ◽

Maria V. Gatsanoga ◽

Maria M. Gradinar ◽

...

Keyword(s):

Blood Brain Barrier ◽

Intravenous Administration ◽

Functional Activity ◽

Brain Barrier ◽

Renal Tubules ◽

Parkinson's Syndrome ◽

Parkinson’S Syndrome ◽

P Glycoprotein ◽

Blood Brain ◽

The Brain

Background. P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter with broad substrate specificity that is localized in hepatocytes, enterocytes, epithelial renal tubules, and also in tissue barriers, including blood-brain barrier (BBB). Increased Pgp activity in BBB is one of the reasons for the pharmacoresistance of a number of CNS diseases. Aim. Analysis of Pgp functional activity in BBB during experimental Parkinson's syndrome. Materials and Methods. The work was performed on 90 Wistar rats, divided into 3 series (n=30 in each). The 1 series (control) was subcutaneously injected sunflower oil once a day for 7 days, and Pgp activity in BBB was assessed on the 8th day. The 2 and 3 series (pathology control) - were administered rotenone at a dose of 2.5 mg/kg once a day for 7 and 28 days respectively to simulate parkin-sonism. At the end of the experiment Pgp activity was estimated. To confirm Parkinson's syndrome, in addition to the clinical picture, level of dopamine in midbrain and striatum was determined using enzyme-linked immunosorbent assay. Pgp functional activity in BBB was assessed by the degree of penetration of its marker substrate fexofenadine into the brain after its intravenous administration at a dose of 10 mg/kg. The content of fexofenadine in the blood plasma and in brain tissue was estimated by the area under pharmacokinetic curve of the substance (in the blood or brain tissues) - AUC0-t(plasma) or AUC0-t(brain) respectively. To assess the BBB permeability the ratio AUC0-t(brain) / AUC0-t(plasma) was calculated. Results. Rotenone administration led to the development of parkinsonism typical picture: muscle stiffness, hypokinesia, gait instability. There was a decrease in dopamine level in the striatum after 7 days by 69.6% (p=0.095), after 28 days - by 93.9% (p=0.008), in midbrain - by 72.7% (p=0.095) and 68.7% (p=0.032) respectively. Fexofenadine AUC0-t(plasma) and AUC0-t(brain) after its intravenous administration to control rats were 266.2 (246.4; 285.6) μg/ml*min and 5.9 (5.8;6.6) µg/g*min respectively, AUC0-t(brain) /AUC0-t(plasma) - 0.020 (0.019; 0.022). When rotenone was for 7 days administered - fexofenadine AUC0-t(brain) increased 2.02 times (p=0.0163), AUC0-t(brain) / AUC0-t(plasma) - 2.4 times (p=0.0283). 28 days administration of rotenone led to augmentation of AUC0-t(brain) of fexofenadine by 1.75 times (p=0.0283), AUC0-t(brain) / AUC0-t(plasma) - by 2.27 times (p=0.0163). Conclusions. The development of Parkinson’s syndrome, caused by the administration of rotenone, inhibits Pgp functional activity in BBB, which is confirmed by the accumulation in the brain marker substrate of the transporter - fexofenadine.

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Accumulation and Removal of Hg203 in Different Regions of the Rat Brain

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100024161 ◽

1978 ◽

Vol 5 (4) ◽

pp. 397-400 ◽

Cited By ~ 12

Author(s):

R.F. Butterworth ◽

M. Gonce ◽

A. Barbeau

Keyword(s):

Rat Brain ◽

Medulla Oblongata ◽

Intravenous Administration ◽

Methyl Mercury ◽

Regional Distribution ◽

Early Peak ◽

The Brain

SUMMARY:We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid.

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Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029400500504 ◽

1994 ◽

Vol 5 (5) ◽

pp. 304-311 ◽

Cited By ~ 2

Author(s):

K. J. Doshi ◽

F. D. Boudinot ◽

J. M. Gallo ◽

R. F. Schinazi ◽

C. K. Chu

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Oral Administration ◽

Intravenous Administration ◽

Brain Targeting ◽

The Central Nervous System ◽

Intravenous And Oral Administration ◽

The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

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