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Effect of stroke on the transcriptome of lamina propria macrophages in the small intestines

ABSTRACT: To investigate the effect of stroke on the trasnscriptome of intestinal lamina propria macrophages, mice underwent permanent middle cerebral artery occlusion (pMCAO) or sham surgery for 24 hours

ORGANISM(S): Mus musculus

PROVIDER: GSE216971 | GEO | 2024/03/24

REPOSITORIES: GEO

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Effect of stroke on the transcriptome of lamina propria macrophages in the small intestines

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Data in support of administration of a soluble TNF inhibitor that reduces infarct volume after focal cerebral ischemia in mice

Project description:Background: Tumor necrosis factor, which exists both as a soluble (solTNF) and a transmembrane (tmTNF) protein, plays an important role in post-stroke inflammation. The objective of the present study was to test the effect of topical versus intracerebroventricular administration of XPro1595 (a solTNF inhibitor) and etanercept (a solTNF and tmTNF inhibitor) compared to saline on output measures such as infarct volume and post-stroke inflammation in mice. Methods: Adult male C57BL/6 mice were treated topically (2.5 mg/ml/1µl/hr for 3 consecutive days) or intracerebroventricularly (1.25 mg/kg/0.5 ml, once) with saline, XPro1595, or etanercept immediately after permanent middle cerebral artery occlusion (pMCAO). Mice were allowed to survive 1 or 3 days. Infarct volume, microglial and leukocyte profiles, and inflammatory markers were evaluated. Results: We found that topical, and not intracerebroventricular, administration of XPro1595 reduced infarct volume at both 1 day and 3 days after pMCAO. Etanercept showed no effect. We observed no changes in microglial or leukocyte populations. XPro1595 increased gene expression of P2ry12 at 1 day and Trem2 at 1 and 3 days, while decreasing Cx3cr1 expression at 1 and 3 days after pMCAO, suggesting a change in microglial activation towards a phagocytic phenotype. Conclusions: Our data demonstrate that topical administration of XPro1595 for three consecutive days decreases infarct volumes after ischemic stroke, while modifying microglial activation and the inflammatory response post-stroke. This suggests that inhibitors of solTNF hold great promise for future neuroprotective treatment in ischemic stroke.

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Whole-genome microarrays in the ischemic penumbra of mice and rats 2hrs and 6hrs after permanent middle cerebral artery occlusion (pMCAO)

Project description:Neuroprotection has not been successfully translated from animals to humans, and controversies persist about the suitability of animal models for the evaluation of putative stroke therapies. Of these, many appear to be less effective in mice as compared with rats. We hypothesized that this may be due to fundamental interspecies differences in stroke response. Whole-genome microarrays were used to examine differential gene regulation in the ischemic penumbra of mice and rats 2hrs and 6hrs after permanent middle cerebral artery occlusion (pMCAO). The differentially expressed genes in the ischemic penumbra at each time point were compared between the two species.

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