Stem Cell-Like Dog Placenta Cells Afford Neuroprotection against Ischemic Stroke Model via Heat Shock Protein Upregulation

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis of Caenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factor egl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.

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Downregulation of miR-181b in mouse brain following ischemic stroke induces neuroprotection against ischemic injury through targeting heat shock protein A5 and ubiquitin carboxyl-terminal hydrolase isozyme L1

Journal of Neuroscience Research ◽

10.1002/jnr.23255 ◽

2013 ◽

Vol 91 (10) ◽

pp. 1349-1362 ◽

Cited By ~ 63

Author(s):

Zhifeng Peng ◽

Jiefei Li ◽

Yun Li ◽

Xuan Yang ◽

Sujuan Feng ◽

...

Keyword(s):

Ischemic Stroke ◽

Heat Shock ◽

Heat Shock Protein ◽

Mouse Brain ◽

Ischemic Injury ◽

Carboxyl Terminal

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Neural Stem Cell Extracellular Vesicles Disrupt Midline Shift Predictive Outcomes in Porcine Ischemic Stroke Model

Translational Stroke Research ◽

10.1007/s12975-019-00753-4 ◽

2019 ◽

Vol 11 (4) ◽

pp. 776-788 ◽

Cited By ~ 5

Author(s):

Samantha E. Spellicy ◽

Erin E. Kaiser ◽

Michael M. Bowler ◽

Brian J. Jurgielewicz ◽

Robin L. Webb ◽

...

Keyword(s):

Stem Cell ◽

Ischemic Stroke ◽

Functional Outcome ◽

Neural Stem Cell ◽

Functional Outcomes ◽

Extracellular Vesicle ◽

Stroke Model ◽

Midline Shift ◽

Post Stroke ◽

Non Invasive

AbstractMagnetic resonance imaging (MRI) is a clinically relevant non-invasive imaging tool commonly utilized to assess stroke progression in real time. This study investigated the utility of MRI as a predictive measure of clinical and functional outcomes when a stroke intervention is withheld or provided, in order to identify biomarkers for stroke functional outcome under these conditions. Fifteen MRI and ninety functional parameters were measured in a middle cerebral artery occlusion (MCAO) porcine ischemic stroke model. Multiparametric analysis of correlations between MRI measurements and functional outcome was conducted. Acute axial and coronal midline shift (MLS) at 24 h post-stroke were associated with decreased survival and recovery measured by modified Rankin scale (mRS) and were significantly correlated with 52 measured acute (day 1 post) and chronic (day 84 post) gait and behavior impairments in non-treated stroked animals. These results suggest that MLS may be an important non-invasive biomarker that can be used to predict patient outcomes and prognosis as well as guide therapeutic intervention and rehabilitation in non-treated animals and potentially human patients that do not receive interventional treatments. Neural stem cell–derived extracellular vesicle (NSC EV) was a disruptive therapy because NSC EV administration post-stroke disrupted MLS correlations observed in non-treated stroked animals. MLS was not associated with survival and functional outcomes in NSC EV–treated animals. In contrast to untreated animals, NSC EVs improved stroked animal outcomes regardless of MLS severity.

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