Brain-on-a-chip microsystem for investigating traumatic brain injury: Axon diameter and mitochondrial membrane changes play a significant role in axonal response to strain injuries

Dollé, Jean-Pierre; Morrison, Barclay; Schloss, Rene S.; Yarmush, Martin L.

doi:10.1142/s2339547814500095

Cited by 33 publications

(39 citation statements)

References 56 publications

(82 reference statements)

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“…Most of the recent BMPS published are entirely focused on neurons and not glial populations (Park et al, 2015; Dolle et al, 2014). Since astrocytes and oligodendrocytes play important roles during neuronal development, plasticity and injury, the presence of glial cell populations in this BMPS model provides an excellent opportunity for the evaluation of neuronal-glial interactions and the role of glia in pathogenesis and toxicity processes.…”

Section: Discussionmentioning

confidence: 99%

A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity

Pamies

Barreras

Block

et al. 2017

ALTEX

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Summary Human in vitro models of brain neurophysiology are needed to investigate molecular and cellular mechanisms associated with neurological disorders and neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain microphysiological system (BMPS), comprised of differentiated mature neurons and glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial interactions and connectivity. BMPS mature over eight weeks and show the critical elements of neuronal function: synaptogenesis and neuron-to-neuron (e.g., spontaneous electric field potentials) and neuronal-glial interactions (e.g., myelination), which mimic the microenvironment of the central nervous system, rarely seen in vitro before. The BMPS shows 40% overall myelination after 8 weeks of differentiation. Myelin was observed by immunohistochemistry and confirmed by confocal microscopy 3D reconstruction and electron microscopy. These findings are of particular relevance since myelin is crucial for proper neuronal function and development. The ability to assess oligodendroglial function and mechanisms associated with myelination in this BMPS model provide an excellent tool for future studies of neurological disorders such as multiple sclerosis and other demyelinating diseases. The BMPS provides a suitable and reliable model to investigate neuron-neuroglia function as well as pathogenic mechanisms in neurotoxicology.

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Section: Discussionmentioning

confidence: 99%

A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity

Pamies

Barreras

Block

et al. 2017

ALTEX

189

188

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“…In a similar approach, Yap et al () designed a microfluidic device (Table ) to induce strain injury to dissociated rat cortical axons. Unlike Dolle's strain injury model (Dolle et al, ; Dolle et al, ) which applied injury to axons over 2 mm, this device applies a localized stretch injury to axons over 90 μm. A very mild stretch, or a mild stretch, consisting of 0.5% strain or 5% strain, respectively, was applied, and it was observed that a very mild stretch did not have significant axonal degeneration 1 day following injury, but did have significant degeneration 3 days post injury.…”

Section: Physical (Stretch/strain) Injurymentioning

confidence: 99%

Microfluidic platforms for the study of neuronal injury in vitro

Shrirao

Kung

Omelchenko

et al. 2018

Biotech & Bioengineering

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Traumatic brain injury (TBI) affects 5.3 million people in the United States, and there are 12,500 new cases of spinal cord injury (SCI) every year. There is yet a significant need for in vitro models of TBI and SCI in order to understand the biological mechanisms underlying central nervous system (CNS) injury and to identify and test therapeutics to aid in recovery from neuronal injuries. While TBI or SCI studies have been aided with traditional in vivo and in vitro models, the innate limitations in specificity of injury, isolation of neuronal regions, and reproducibility of these models can decrease their usefulness in examining the neurobiology of injury. Microfluidic devices provide several advantages over traditional methods by allowing researchers to (1) examine the effect of injury on specific neural components, (2) fluidically isolate neuronal regions to examine specific effects on subcellular components, and (3) reproducibly create a variety of injuries to model TBI and SCI. These microfluidic devices are adaptable for modeling a wide range of injuries, and in this review, we will examine different methodologies and models recently utilized to examine neuronal injury. Specifically, we will examine vacuum-assisted axotomy, physical injury, chemical injury, and laser-based axotomy. Finally, we will discuss the benefits and downsides to each type of injury model and discuss how researchers can use these parameters to pick a particular microfluidic device to model CNS injury.

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“…Using laser microbeam dissection within a micropatterned substrate could produce precise zones of neuronal injury, and shows te potential for high-throughput screening of agents to promote neuronal regeneration though laser-associated damage is quite different from the actual trauma or spinal cord injury. Also, a traumatic brain injury (TBI) model was developed on a similar microdevice, which can apply uniaxial pressure to make strained axons that consequently emulate a diffused axonal injury [ 93 ] ( Figure 4 b). It is suggested that the axonal diameter plays a significant role in strain injury, which mimics the cause of TBI.…”

Section: Neuronal Disease Models On the Nervous System-on-a-chipmentioning

confidence: 99%

Microdevice Platform for In Vitro Nervous System and Its Disease Model

2017

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The development of precise microdevices can be applied to the reconstruction of in vitro human microenvironmental systems with biomimetic physiological conditions that have highly tunable spatial and temporal features. Organ-on-a-chip can emulate human physiological functions, particularly at the organ level, as well as its specific roles in the body. Due to the complexity of the structure of the central nervous system and its intercellular interaction, there remains an urgent need for the development of human brain or nervous system models. Thus, various microdevice models have been proposed to mimic actual human brain physiology, which can be categorized as nervous system-on-a-chip. Nervous system-on-a-chip platforms can prove to be promising technologies, through the application of their biomimetic features to the etiology of neurodegenerative diseases. This article reviews the microdevices for nervous system-on-a-chip platform incorporated with neurobiology and microtechnology, including microfluidic designs that are biomimetic to the entire nervous system. The emulation of both neurodegenerative disorders and neural stem cell behavior patterns in micro-platforms is also provided, which can be used as a basis to construct nervous system-on-a-chip.

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Brain-on-a-chip microsystem for investigating traumatic brain injury: Axon diameter and mitochondrial membrane changes play a significant role in axonal response to strain injuries

Cited by 33 publications

References 56 publications

A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity

A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity

Microfluidic platforms for the study of neuronal injury in vitro

Microdevice Platform for In Vitro Nervous System and Its Disease Model

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