Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

Translation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scop...

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Bibliographic Details
Published in:Cellular and molecular neurobiology 2023-10, Vol.43 (7), p.3137-3160
Main Authors: Voogd, Eva J. H. F., Frega, Monica, Hofmeijer, Jeannette
Format: Article
Language:English
Subjects:
Animal models
Apoptosis
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell death
Hypoxia
Inflammation
Ischemia
Literature reviews
Neural networks
Neural stem cells
Neurobiology
Neuroblastoma
Neuroprotection
Neurosciences
Oxidative stress
Pluripotency
Review Paper
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Summary:Translation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scoping review of the literature on human neuronal in vitro models that have been used to study neuronal responses to ischemia or hypoxia, the parts of the pathophysiological cascade that have been investigated in those models, and evidence on effects of interventions. We included 147 studies on four different human neuronal models. The majority of the studies (132/147) was conducted in SH-SY5Y cells, which is a cancerous cell line derived from a single neuroblastoma patient. Of these, 119/132 used undifferentiated SH-SY5Y cells, that lack many neuronal characteristics. Two studies used healthy human induced pluripotent stem cell derived neuronal networks. Most studies used microscopic measures and established hypoxia induced cell death, oxidative stress, or inflammation. Only one study investigated the effect of hypoxia on neuronal network functionality using micro-electrode arrays. Treatment targets included oxidative stress, inflammation, cell death, and neuronal network stimulation. We discuss (dis)advantages of the various model systems and propose future perspectives for research into human neuronal responses to ischemia or hypoxia. Graphical Abstract
ISSN:0272-4340
1573-6830
DOI:10.1007/s10571-023-01368-y