Current ex vivo and in vitro approaches to uncovering mechanisms of neurological dysfunction after traumatic brain injury

Hamilton, Kelly; Santhakumar, Vijayalakshmi

doi:10.1016/j.cobme.2020.05.001

Cited by 7 publications

(4 citation statements)

References 54 publications

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“…For example, cerebral organoids are being used in research investigating what occurs in the brain of people with post-traumatic stress disorder (PTSD). 51 These experiments, while valuable, have limitations because, although they produce cortisol readouts to show what happens when stress is induced, there is no experiential aspect that can be qualitatively interpreted. This is important, because PTSD is a debilitating and serious condition that causes profound and persistent distress.…”

Section: Experiential Aspects Of Diseasementioning

confidence: 99%

Cerebral Organoid Research Ethics and Pinning the Tail on the Donkey

McKeown

2023

Camb Q Healthc Ethics

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The risk of creating cerebral organoids/assembloids conscious enough to suffer is a recurrent concern in organoid research ethics. On one hand, we should, apparently, avoid discovering how to distinguish between organoids that it would be permissible (non-conscious) and impermissible (conscious) to use in research, since if successful we would create organoids that suffer. On the other, if we do not, the risk persists that research might inadvertently continue to cause organoids to suffer. Moreover, since modeling some brain disorders may require inducing stress in organoids, it is unclear how to eliminate the risk, if we want to develop effective therapies. We are committed to harm avoidance but hamstrung by a presumption that we should avoid research that might tell us clearly when suffering occurs. How can we negotiate this challenge and maximize the therapeutic benefits of cerebral organoid research? The author interrogates the challenge, suggesting a tentative way forward.

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Section: Experiential Aspects Of Diseasementioning

confidence: 99%

Cerebral Organoid Research Ethics and Pinning the Tail on the Donkey

McKeown

2023

Camb Q Healthc Ethics

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“…Cellular in vitro platforms used up until now to model TBI and stroke are brain slices, organotypic cell cultures, primary neuronal cells, immortalized cell lines, and different types of stem cells of human and rodent origin [2,24,25]. In the in vitro studies of TBI, most used cells are the ones of rodent origin, and of those rats account for about 70 % [2].…”

Section: Cell Culture Platforms Used In Traumatic Brain Injury and Br...mentioning

confidence: 99%

“…However, the technique of obtaining the tissue slices requires that it is cut out, and this trauma itself could be used as an injury model [25]. As an example, it has been found that organotypic slices develop epileptiform activity after a week in culture that resembles changes related to the post-traumatic epilepsy [56].…”

Section: Organotypic Slice Culturesmentioning

confidence: 99%

Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies

et al. 2022

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The central nervous system (CNS) injury, which occurs because of mechanical trauma or ischemia/hypoxia, is one of the main causes of mortality and morbidity in the modern society. Until know, despite the fact that numerous preclinical and clinical studies have been undertaken, no significant neuroprotective strategies have been discovered that could be used in the brain trauma or ischemia treatment. Although there are many potential explanations for the failure of those studies, it is clear that there are questions regarding the use of experimental models, both in vivo and in vitro, when studying CNS injury and searching new therapeutics. Due to some ethical issues with the use of live animals in biomedical research, implementation of experimental strategies that prioritize the use of cells and tissues in the in vitro environment has been encouraged. In this review, we examined some of the most commonly used in vitro models and the most frequently utilized cellular platforms in the research of traumatic brain injury and cerebral ischemia. We also proposed some future strategies that could improve the usefulness of these studies for better bench-to-bedside translational outcomes.

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“…The existence of a wide range of in vitro TBI models has been well documented. 13 , 14 In the context of penetrating injuries, one approach is to perform a transection, which directly injures multiple cells while exposing surrounding cells to secondary effects. However, this method, though easily scalable and suitable for high-throughput screenings, is limited in its ability to model a small percentage of clinically relevant brain injuries.…”

Section: Introductionmentioning

confidence: 99%

Inducing Mechanical Stimuli to Tissues Grown on a Magnetic Gel Allows Deconvoluting the Forces Leading to Traumatic Brain Injury

Schlotterose,

Beldjilali-Labro,

Hagel

et al. 2023

Neurotrauma Reports

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Traumatic brain injury (TBI), which is characterized by damage to the brain resulting from a sudden traumatic event, is a major cause of death and disability worldwide. It has short- and long-term effects, including neuroinflammation, cognitive deficits, and depression. TBI consists of multiple steps that may sometimes have opposing effects or mechanisms, making it challenging to investigate and translate new knowledge into effective therapies. In order to better understand and address the underlying mechanisms of TBI, we have developed an in vitro platform that allows dynamic simulation of TBI conditions by applying external magnetic forces to induce acceleration and deceleration injury, which is often observed in human TBI. Endothelial and neuron-like cells were successfully grown on magnetic gels and applied to the platform. Both cell types showed an instant response to the TBI model, but the endothelial cells were able to recover quickly—in contrast to the neuron-like cells. In conclusion, the presented in vitro model mimics the mechanical processes of acceleration/deceleration injury involved in TBI and will be a valuable resource for further research on brain injury.

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Current ex vivo and in vitro approaches to uncovering mechanisms of neurological dysfunction after traumatic brain injury

Cited by 7 publications

References 54 publications

Cerebral Organoid Research Ethics and Pinning the Tail on the Donkey

Cerebral Organoid Research Ethics and Pinning the Tail on the Donkey

Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies

Inducing Mechanical Stimuli to Tissues Grown on a Magnetic Gel Allows Deconvoluting the Forces Leading to Traumatic Brain Injury

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