Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with singlephoton emission computerized tomography imaging

Laske, Douglas W.; Morrison, Paul F.; Lieberman, Daniel M.; Corthesy, Mark E.; Reynolds, James C.; Stewart-Henney, Patricia A.; Koong, Sung-Soo; Cummins, Alex; Paik, Chang H.; Oldfield, Edward H.

doi:10.3171/jns.1997.87.4.0586

Cited by 137 publications

(57 citation statements)

References 13 publications

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“…43 Convection-enhanced delivery, a method of infusing pharmacological agents into the extracellular space of the brain, has been used to treat a variety of brain diseases. 5,8,21,22,24,26,32,33,35 Convection utilizes the pressure of a syringe infusion pump transmitted to the catheter tip to move the fluid that contains the therapeutic agent throughout the extracellular space of the brain in the perfused region from which it can exchange with brain cells. This delivery technique was safe when used to deliver an immunotoxin to brain tumors in humans 22 and has been used successfully to deliver Nmethyl-D-aspartate-receptor excitotoxins to selectively eliminate the neuronal population of the GPI in primates with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.…”

Section: Discussionmentioning

confidence: 99%

Local distribution and toxicity of prolonged hippocampal infusion of muscimol

Heiss¹,

Walbridge²,

Morrison³

et al. 2005

Journal of Neurosurgery

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Object-The activity of γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode.Methods-Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed.Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter.Conclusions-Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy.

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Section: Discussionmentioning

confidence: 99%

Local distribution and toxicity of prolonged hippocampal infusion of muscimol

Heiss¹,

Walbridge²,

Morrison³

et al. 2005

Journal of Neurosurgery

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“…7,16,19 Data from studies in the cat and nonhuman primate brain have shown that CED allows uniform distribution of infusate, covering distances of 1 to 2.9 cm from the site of catheter placement. 3, 12 Hadaczek and colleagues 6 have demonstrated that CED-mediated infusion of adenoassociated virus in a 35.5-μl volume covered nearly 75% of the putamen in rhesus monkeys. The distribution of infused liposomes or viral vectors can be increased further when mannitol is coadministered to increase the size of the interstitial space and to promote diffusion.…”

Section: Introductionmentioning

confidence: 99%

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter

Oh¹,

Odland

Wilson

et al. 2007

JNS

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Object-A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused.Methods-Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle.Results-Hollow fiber catheter-mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that cathetermediated infusion of adenovirus resulted in gene expression that was 10 times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere.Conclusions-The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED.

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“…Therefore, alternative strategies have been developed for delivering nanoparticles to affected brain tissue. Intracranial infusion, or convection-enhanced delivery (CED), has been used to deliver low molecular weight molecules [2,25,1], proteins [24,23,26], and several kinds of particles, including liposomes [28,42,43,19,44,36] and polymeric nanoparticles [6]. Although small molecules and some proteins can be distributed throughout the brain with CED, it has proven difficult to distribute nanoparticles over comparable distances.…”

Section: Introductionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain. Monodisperse polystyrene particles with a diameter of 54 nm were used as a model nanoparticle system. Because the size of these particles is comparable to the effective pore size of the ECM, their transport may be significantly hindered compared with the transport of low molecular weight molecules. To enhance the transport of the infused nanoparticles, we attempted to increase the effective pore size of the ECM by two methods: dilating the extracellular space and degrading selected constituents of the ECM. Two methods of dilating the extracellular space were investigated: co-infusion of nanoparticles and a hyperosmolar solution of mannitol, and pre-infusion of an isotonic buffer solution followed by infusion of nanoparticles. These treatments resulted in an increase in the nanoparticle distribution volume of 50% and 123%, respectively. To degrade hyaluronan, a primary structural component of the brain ECM, a pre-infusion of hyaluronidase (20,000 U/mL) was followed after 30 min by infusion of nanoparticles. This treatment resulted in an increase in the nanoparticle distribution of 64%. Our results suggest that both dilation and enzymatic digestion can be incorporated into CED protocols to enhance nanoparticle penetration.

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Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with singlephoton emission computerized tomography imaging

Cited by 137 publications

References 13 publications

Local distribution and toxicity of prolonged hippocampal infusion of muscimol

Local distribution and toxicity of prolonged hippocampal infusion of muscimol

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

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