Use of Implantable Pumps for Central Nervous System Drug Infusions to Treat Neurological Disease

Harbaugh, Robert E.; Saunders, Richard L.; Reeder, Ralph F.

doi:10.1227/00006123-198812000-00001

Cited by 61 publications

(13 citation statements)

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“…Osmotic minipumps are commonly used for delivering substances over a long period of time (Harbaugh et al, 1988). In our studies, plasma cocaine concentrations were measured to determine whether there was any variability due to partial occlusion of the pumps, which can occur over a period of time (Jones et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Diffusion tensor imaging of cocaine-treated rodents

Narayana¹,

Ahobila-Vajjula²,

Ramu³

et al. 2009

Psychiatry Research: Neuroimaging

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Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared to non-drug using controls. It is not known whether the FA differences seen on DTI in white matter regions of cocaine-dependent humans result from a preexisting predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed 18% decrease in fractional anisotropy (FA) in the splenium of corpus callosum (CC) in cocaine-administered animals relative to saline controls (P = 0.0001). On histology, significant increase in neurofilament expression (125%, P=0.0044) and decrease in myelin basic protein (40%, P = 0.031) was observed in the same region in cocaine-administered animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to a several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration.

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Section: Discussionmentioning

confidence: 99%

Diffusion tensor imaging of cocaine-treated rodents

Narayana¹,

Ahobila-Vajjula²,

Ramu³

et al. 2009

Psychiatry Research: Neuroimaging

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“…This is invasive and expensive to perform and may only be useful for acute administration of drugs. Nevertheless, direct injections into the CNS could be a useful way of introducing longer‐acting slow‐release preparations, implanted devices 51 or genetically modified cells that are able to produce drugs in situ , secreting them directly into the CNS 52 …”

Section: Strategies That Do Not Involve Modifications In the Moleculamentioning

confidence: 99%

Barrier Mechanisms in the Brain, I. Adult Brain

Saunders

Habgood

Dzięgielewska

1999

Clin Exp Pharma Physio

145

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SUMMARY1. The adult brain functions within a well-controlled (internal) environment that is separate from that of the internal environment of the rest of the body as a whole.2. The underlying mechanism of control of the brain's internal environment lies in the presence of tight junctions between the cerebral endothelial cells at the blood-brain interface (blood-brain barrier) and between choroid plexus epithelial cells (blood-cerebrospinal fluid (CSF) barrier).3. The effect of tight junctions at the blood-brain and blood-CSF barriers is to convert the properties of the individual endothelial and epithelial cells into properties of these interfaces as a whole.4. Superimposed on the diffusion restriction provided by the tight junctions in the blood-brain and blood-CSF barriers is a series of transport mechanisms into and out of the brain and CSF that determine and control the internal environment of the brain with respect to a wide range of molecules, such as electrolytes, amino acids, glucose, vitamins and peptides.5. The physical characteristics of drugs, together with their interaction with the properties of the barriers between blood, brain and CSF, determine the extent to which drugs penetrate into the brain.6. Drugs can be targeted to the brain by making use of knowledge of this interaction between the physical properties of a drug (which can be modified by manipulation of the structure of the molecule in predictable ways) and the influx/efflux mechanisms present in the blood-CSF and blood-brain interfaces.Key words: blood-brain barrier, brain vessel permeability, cerebral endothelium, cerebrospinal fluid, choroid plexus, drug delivery, drug permeability, P-glycoprotein, sink effect, tight junctions. INTRODUCTIONIn the adult, the brain functions within a well-controlled local (internal) environment that is distinct from the general internal environment of the body as a whole. The mechanisms that control this stable internal environment within the brain are often collectively and colloquially known as 'the blood-brain barrier'. Originally, the term 'barrier' was used to explain the results of experiments that showed that certain dyes and bacterial toxins injected into animals were kept out of the brain, 1,2 but did stain or have toxic effects on the brain if injected into it. 2,3 Lewandowsky, who studied penetration of potassium ferrocyanide into the brain, appears to have been the first to use the term blood-brain barrier ('bluthirnschranke'). 4 Later studies showed that dyes excluded from the brain are so excluded because they are bound to proteins, 5 so the 'barrier' is, in fact, to large molecules.The explanation for the restriction of protein entry into the brain is that endothelial cells lining cerebral vessels are joined by continuous tight junctions that seal off the intercellular space effectively against all but perhaps the smallest molecules. These junctions effectively convert the endothelial cell layer into a single interface between the blood and the brain extracellular fluid. Thus, the properti...

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“…However, both techniques used in this study have advantages and disadvantages. Some aspects of this issue have been discussed previously (Harbaugh et al, 1988;Williams et al, 1987).…”

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confidence: 99%

Infusion of cytosine‐arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury

Svensson

Aldskogius

1993

Glia

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The present study describes a method to inhibit selectively the microglial cell proliferation following peripheral nerve injury. Continuous infusion of cytosine-arabinoside (ARA-C) from an osmotic minipump to the fourth ventricle or cisterna magna completely blocks the proliferation of microglial cells that normally occurs following hypoglossal nerve transection. This treatment had no significant effect on other glial cells or on the expected morphological changes in the axotomized hypoglossal motorneurons. The method opens up new possibilities for analyzing the functional role of the axotomy-induced microglial cell reaction.

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Use of Implantable Pumps for Central Nervous System Drug Infusions to Treat Neurological Disease

Cited by 61 publications

References 0 publications

Diffusion tensor imaging of cocaine-treated rodents

Diffusion tensor imaging of cocaine-treated rodents

Barrier Mechanisms in the Brain, I. Adult Brain

Infusion of cytosine‐arabinoside into the cerebrospinal fluid of the rat brain inhibits the microglial cell proliferation after hypoglossal nerve injury

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