Characterization of neutrophil-neuronal co-cultures to investigate mechanisms of post-ischemic immune-mediated neurotoxicity

Mai, Nguyen; Prifti, Viollandi; Kim, Min‐Soo; Halterman, Marc W.

doi:10.1016/j.jneumeth.2020.108782

Cited by 7 publications

(9 citation statements)

References 60 publications

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“…The anti-inflammatory activity of PNX is associated with decreased expression of cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Moreover, PNX reduces the release of ROS and increases the production of anti-inflammatory glutathione [69]. Consistently, the protective effects of PNX against I/R injury reduces the infarct volume as well as suppressing the microglia activation in a middle cerebral artery occlusion rat model.…”

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinsupporting

confidence: 56%

“…The role of PNX in I/R and ischemic stroke was explored in microglia, and the effects of PNX on cell death and neuronal damage were studied [30]. Oxygen-glucose deprivation/reperfusion leads to acute inflammatory response and increases the secretion of proinflammatory cytokines and reactive oxygen species (ROS) in microglia [69]. Ma et al, have demonstrated that PNX protects against neuronal damage and inhibits cell death in murine microglial BV2 cells.…”

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

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Phoenixin: More than Reproductive Peptide

Billert

Rak

Nowak

et al. 2020

IJMS

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Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the central nervous system (CNS) and in the female reproductive system where it potentiates LH secretion and controls the estrus cycle. Moreover, it stimulates oocyte maturation and increases the number of ovulated oocytes. Nevertheless, PNX not only regulates the reproduction system but also exerts anxiolytic, anti-inflammatory, and cell-protective effects. Furthermore, it is involved in behavior, food intake, sensory perception, memory, and energy metabolism. Outside the CNS, PNX exerts its effects on the heart, ovaries, adipose tissue, and pancreatic islets. This review presents all the currently available studies demonstrating the pleiotropic effects of PNX.

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Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinsupporting

confidence: 56%

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

Phoenixin: More than Reproductive Peptide

Billert

Rak

Nowak

et al. 2020

IJMS

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“…In unstimulated conditions, neutrophils made physical contact with neuronal cell body and dendrites resulting in disruptions to neurite outbranching and fragmentation. When undergoing OGD, the neurite length significantly decreased, indicating that neutrophils were detrimental to neuronal morphology and survivability under normo‐ or hypoxic conditions 85 . Although no assessments of neutrophil phenotype were made in these earlier in vitro studies, these results indicate that neutrophils may have an inherent toxicity toward neurons, which may be amplified during cerebral ischemia.…”

Section: Impact Of Neutrophils On Neuronal Damage In Strokementioning

confidence: 92%

Dynamic roles of neutrophils in post‐stroke neuroinflammation

2021

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Clinical trials involving the blockage of peripheral inflammatory leukocyte recruitment into the brain have puzzlingly led to either no significant improvement in stroke outcome, or even worsened outcomes and increased mortality, prompting a re-evaluation of our understanding into the neuroinflammatory processes after stroke. Whilst traditionally understood as simple effectors of the innate immune system, emerging research in vascular disease biology has redefined the neutrophil as a specialized and highly specific cell type with dynamic functional capacity. Indeed, emerging experimental evidence indicates that neutrophils display diverse roles in the acute stages of ischemic stroke with the ability to elicit both pro-inflammatory and antiinflammatory effects. Currently, there is some uncertainty as to whether neutrophil diversity is beneficial or harmful in stroke as their interactions with the resident cells of the brain, such as microglia and neurons, would potentially elicit heterogeneous outcomes. Current treatments for patients with stroke aim to remove the vascular blockage and to restore blood flow, but there are currently no drug treatments for managing the loss of functional brain tissue nor restoration of microglial and neuronal damage. If these hypothesized wound-healing functions of neutrophils can be validated in a stroke setting, promoting the recruitment of this type of neutrophils into the injured brain tissue may form a promising therapeutic target for the majority of stroke patients currently without treatment. In this review, we will provide an update on recent research that has explored neutrophil heterogeneity in the neuroinflammatory cascade after ischemic stroke.

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“…2D Co-culture system of primary neuron A 2D co-culture system of primary neurons established by directly mixing different types of cells or sandwich culture is suitable for exploring the interaction between neurons and glial cells, immune cells, and other different types of cells (Mai et al, 2020). For example, a 2D co-culture system of primary neuron and glial cells were applied in the study of neuro-glial synaptic connection (Wang Y. S. et al, 2021).…”

Section: Modalitiesmentioning

confidence: 99%

Recent progresses in novel in vitro models of primary neurons: A biomaterial perspective

Zhang

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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Central nervous system (CNS) diseases have been a growing threat to the health of humanity, emphasizing the urgent need of exploring the pathogenesis and therapeutic approaches of various CNS diseases. Primary neurons are directly obtained from animals or humans, which have wide applications including disease modeling, mechanism exploration and drug development. However, traditional two-dimensional (2D) monoculture cannot resemble the native microenvironment of CNS. With the increasing understanding of the complexity of the CNS and the remarkable development of novel biomaterials, in vitro models have experienced great innovation from 2D monoculture toward three-dimensional (3D) multicellular culture. The scope of this review includes the progress of various in vitro models of primary neurons in recent years to provide a holistic view of the modalities and applications of primary neuron models and how they have been connected with the revolution of biofabrication techniques. Special attention has been paid to the interaction between primary neurons and biomaterials. First, a brief introduction on the history of CNS modeling and primary neuron culture was conducted. Next, detailed progress in novel in vitro models were discussed ranging from 2D culture, ex vivo model, spheroid, scaffold-based model, 3D bioprinting model, and microfluidic chip. Modalities, applications, advantages, and limitations of the aforementioned models were described separately. Finally, we explored future prospects, providing new insights into how basic science research methodologies have advanced our understanding of the CNS, and highlighted some future directions of primary neuron culture in the next few decades.

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Characterization of neutrophil-neuronal co-cultures to investigate mechanisms of post-ischemic immune-mediated neurotoxicity

Cited by 7 publications

References 60 publications

Phoenixin: More than Reproductive Peptide

Phoenixin: More than Reproductive Peptide

Dynamic roles of neutrophils in post‐stroke neuroinflammation

Recent progresses in novel in vitro models of primary neurons: A biomaterial perspective

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