Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology

Caicedo, H. H.; Hernandez, Maximiliano; Fall, Christopher P.; Eddington, David T.

doi:10.1007/s10544-010-9430-5

Cited by 12 publications

(8 citation statements)

References 19 publications

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“…To study the release of NGF from the PSiO 2 implants, we have used artificial cerebrospinal fluid (aCSF) as a relevant physiological medium, to mimic the brain microenvironment. aCSF is commonly used when studying the brain microenvironment in vitro and emulating in vivo conditions, or when simulating brain perfusion as perfusate for ex vivo experiments . The NGF‐loaded implants were incubated in 2 mL of aCSF and at designated time intervals over a period of 2 months, aliquots were sampled and replaced with fresh aCSF.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Zilony‐Hanin

Rosenberg

Richman

et al. 2019

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Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid‐beta (Aβ)‐induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2‐implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live‐mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Zilony‐Hanin

Rosenberg

Richman

et al. 2019

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“…The attenuated response to cocaine is no doubt a result of the negligible amount of cocaine at point F resulting from diffusion from the injection site as well as the drug being carried away downstream. 40 Of significance, only ∼22.5 μL of pharmacological solution was consumed in a 45 min experiment. Using the traditional perfusion method, 45–90 mL of solution would be required; therefore, the capillary application method represents a 2 000–4 000-fold reduction in chemical consumption.…”

Section: Resultsmentioning

confidence: 99%

Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

et al. 2014

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The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last two decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically-evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500-µm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice, and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo.

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“…Previously we demonstrated precise delivery of fluids including neuroactive chemicals to the acute brain slice preparation using patterned microfluidic substrates [16] , [35] . But control of the neurochemical environment in acute brain slice physiology experiments implies the ability to control gases as well – most obviously oxygen.…”

Section: Discussionmentioning

confidence: 99%

Precise Spatial and Temporal Control of Oxygen within In Vitro Brain Slices via Microfluidic Gas Channels

2012

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The acute brain slice preparation is an excellent model for studying the details of how neurons and neuronal tissue respond to a variety of different physiological conditions. But open slice chambers ideal for electrophysiological and imaging access have not allowed the precise spatiotemporal control of oxygen in a way that might realistically model stroke conditions. To address this problem, we have developed a microfluidic add-on to a commercially available perfusion chamber that diffuses oxygen throughout a thin membrane and directly to the brain slice. A microchannel enables rapid and efficient control of oxygen and can be modified to allow different regions of the slice to experience different oxygen conditions. Using this novel device, we show that we can obtain a stable and homogeneous oxygen environment throughout the brain slice and rapidly alter the oxygen tension in a hippocampal slice. We also show that we can impose different oxygen tensions on different regions of the slice preparation and measure two independent responses, which is not easily obtainable with current techniques.

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Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology

Cited by 12 publications

References 19 publications

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain

Localized Drug Application and Sub-Second Voltammetric Dopamine Release Measurements in a Brain Slice Perfusion Device

Precise Spatial and Temporal Control of Oxygen within In Vitro Brain Slices via Microfluidic Gas Channels

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