Ensuring the Future of Clinical and Basic Stroke Research

Fisher, Marc

doi:10.1161/strokeaha.114.005379

Cited by 1 publication

(1 citation statement)

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“…It is difficult to translate basic science knowledge into clinical stroke applications. 1,2 Although there is some debate as to whether rodent models are relevant, it unlikely that all rodent models are completely invalid or completely predictive for human stroke. Conserved biology throughout evolution suggests that it is more likely that some pathways are the same and some are different when comparing how rodent cells respond to oxygen–glucose deprivation versus human cells.…”

Section: Introductionmentioning

confidence: 99%

Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen–glucose deprivation

Deng

Wang

et al. 2016

J Cereb Blood Flow Metab

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Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

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Section: Introductionmentioning

confidence: 99%