A compartmented neuronal culture system in microdevice format

Ravula, Surendra K.; Wang, Min S.; Asress, Seneshaw; Glass, Jonathan D.; Frazier, A. Bruno

doi:10.1016/j.jneumeth.2006.06.022

Cited by 23 publications

(22 citation statements)

References 31 publications

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“…After the application of the drug, morphological assessments were made by measuring the distance of the axon from the cell body to its tip. These tests showed that only when the drug was applied to the axonal compartment was degeneration evident, leading us to believe that a mechanism local to the distal axon is responsible for vincristine neuropathy (see Table 1) [12,15]. At this drug concentration, axonal degeneration started at day one and was complete (neurites retracted completely to the compartment divider) by the end of two days.…”

Section: A Morphological Observationsmentioning

confidence: 99%

“…The system was assembled as previously described [12]. Briefly, collagen was patterned on a glass electrode substrate using a polydimethylsiloxane mold (PDMS) with channels imprinted.…”

Section: System Assemblymentioning

confidence: 99%

“…Explant cultures of E15 dorsal root ganglia (DRG) from Sprague-Dawley rats were prepared for culture in the microsystem as previously described in [11,12]. Media was Eagle's MEM supplemented with 1% N 2 supplement and 7S NGF (Alomone Labs, Jerusalem, Israel) at 100ng/ml.…”

Section: Culture Protocolmentioning

confidence: 99%

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Spatiotemporal localization of injury potentials in DRG neurons during vincristine-induced axonal degeneration

Ravula

Wang

McClain

et al. 2007

Neuroscience Letters

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The distal to proximal degeneration of axons, or "dying back" is a common pattern of neuropathology in many diseases of the PNS and CNS. A long-standing debate has centered on whether this pattern of neurodegeneration is due to an insult to the cell body or to the axon itself, although it is likely that mechanisms are different for specific disease entities. We have addressed this question in a model system of vincristine-induced axonal degeneration. Here, we created a novel experimental apparatus combining a microfluidic divider with a multielectrode array substrate to allow for independent monitoring of injury-induced electrical activity from dorsal root ganglion (DRG) cell bodies and axons while isolating them into their own culture microenvironments. At specified doses, exposure of the cell body to vincristine caused neither morphological neurodegeneration nor persistent hyperexcitablility. In comparison, exposure of the distal axon to the same dose of vincristine first caused a decrease in the excitability of the axon and then axonal degeneration in a dying back pattern. Additionally, exposure of axons to vincristine caused an initial period of hyperexcitability in the cell bodies, suggesting that a signal is transmitted from the distal axon to the soma during the progression of vincristine-induced axonal degeneration. These data support the proposition that vincristine has a direct neurotoxic effect on the axon.

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Section: A Morphological Observationsmentioning

confidence: 99%

“…The system was assembled as previously described [12]. Briefly, collagen was patterned on a glass electrode substrate using a polydimethylsiloxane mold (PDMS) with channels imprinted.…”

Section: System Assemblymentioning

confidence: 99%

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Spatiotemporal localization of injury potentials in DRG neurons during vincristine-induced axonal degeneration

Ravula

Wang

McClain

et al. 2007

Neuroscience Letters

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“…The unique nature of the Campenot chamber facilitates the selective chemical manipulation of neurotrophic growth factors locally to seek a better understanding of how to develop an environment permissive of axonal regrowth. The onset of microfluidics, the science of fluids in microchannels, called for the revision and refinement of the Campenot chamber culture system as microfluidic devices were developed with Campenot's principles in mind while adopting the novel microfabrication techniques [17]. Frequently based on polydimethylsiloxane, microfluidic devices utilize soft lithography to mold the polymer into compartmentalized chambers connected by microchannels that permit axonal extension but not fluid exchange [18].…”

Section: In Vitro Models Of Axonal Degeneration and Regenerationmentioning

confidence: 99%

Studying Axonal Degeneration and Regeneration Using In Vitro and In Vivo Models: the Translational Potential

Donaldson

Höke

2014

Future Neurol.

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Since the initial studies by Cajal, multiple models of peripheral nerve degeneration and regeneration have been developed to address the ever-increasing complexity of the mechanisms involved in regeneration. In vitro models offer the principal benefit of a system that can be readily manipulated to address specific mechanistic questions in a deconstructed system. However, in vitro models can be overly simplified and intricacies of the interactions between neurons and glia can be lost. In vivo animal models seek to remedy some of these shortcomings, but most in vivo animal systems fail to precisely model human nerve regeneration. Rodent models of chronic nerve regeneration have been developed to better recapitulate human nerve regeneration, but are not widely used. An important development in the field has been the establishment of experimental nerve regeneration in humans, involving the reinnervation of the epidermis after cutaneous axotomy or topical capsaicin application. Use of such human models will likely accelerate the development and evaluation of new drugs that enhance peripheral nerve regeneration. KeywordsGiven the complexity of the human peripheral nervous system, a wide spectrum of models has been developed over the years to advance the field of axonal degeneration and regeneration. Predominantly, these systems of neuronal degenerative and regenerative processes have been established in model organisms, particularly in rodents and occasionally in subhuman primates. These animal systems have significantly advanced the understanding of the molecular mechanisms of how axons degenerate and regenerate and have provided an initial subject to test novel drug therapies and surgical techniques to improve regeneration after human nerve injuries.In vitro animal models have served to simplify the field of study, reducing the variable factors that are inherently present in whole organism systems. With a range of methods available, there is the potential to study the interactions of neuronal and glial cell populations or with the advent of microtechnologies, to more precisely examine regeneration at the level of the individual axon. Narrowing the lens through which to view degeneration and regeneration, in vitro models permit a greater degree of manipulation and control of the microenvironment and the potential for rapid-paced drug-screening investigations.While in vitro techniques offer highly controllable systems of study, in vivo animal models provide a closer resemblance to the human condition of nerve injury and repair. Investigating the recovery process following nerve injury in living organisms permits a more authentic glimpse into regeneration as whole body system interactions are maintained. Preserving the integrity of the neuronal environment, in vivo animal nerve injury and repair methods model the complexity of the nervous system recovery, but lack some of the precision associated with in vitro methods.Developed over the last few decades, human models of regeneration emerged as a promising novel system t...

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“…Such an approach to neural interfaces would render the cultured probe effectively a cell-based biosensor [86]. Prior to being deployed in animal studies, these technologies are developed and tested in vitro in the form of modified planar MEAs [81,[87][88][89][90][91][92]. Much of the work done to date interfacing MEAs with cells in vitro has been performed with applications in two cell systems [86,93]: 1) neurons, where the ability to identify the activity of single cells in spike trains through a process called "spike-sorting" is used to identify patterns of population activity and network dynamics and 2) cardiac myocytes, where spatial and temporal resolution allow the measurement of transduction velocity through sheets of linked cardiomyocytes.…”

Section: Proof Of Principalmentioning

confidence: 99%