I don't know what you were trying to do but boy, you know nothing!
Early transcriptional changes in neutrophil-mediated processes following recanalization after ischemic stroke
Background:
Ischemic stroke is a leading cause of mortality and long-term
disability globally. Current recanalization therapies, including
mechanical thrombectomy and thrombolysis, aim to restore blood flow in
acute ischemic stroke patients. However, many patients with successful
recanalization still experience poor clinical outcomes. This phenomenon,
where the restoration of blood flow does not translate into functional
recovery, is known as futile recanalization. (Wow, you know nothing of the neuronal cascade of death, the recanalization worked, it's just that by not stopping the neuronal cascade of death in the first week, you are letting hundreds of millions to billions of neurons to die! For that incredible stupidity you all deserve to be fired!)
Methods:
Using a murine
middle cerebral occlusion (MCAO) model that mimics a large vessel
occlusion with recanalization, a comprehensive microarray analysis of
gene expression from blood samples collected during MCAO and after
recanalization (N=44) was performed. Results: Il1r2, Cd55, Mmp8, Cd14,
and Cd69 were key regulatory genes expressed early after MCAO and
recanalization. A comparison with gene expression data from human stroke
patients and rat MCAO model (GSE16561 and GSE21136) revealed Vcan as a
differentially expressed gene conserved across species, marking it as a
novel indicator of recanalization that was detected as early as 3 hours
post-recanalization (4 hours post-MCAO) in mice and 24 hours after
recanalization in rats (MCAO-thrombectomy) and humans
(rtPA-thrombolysis). Leukocyte and neutrophil activation pathways were
significantly enriched in the mouse data and human samples from
GSE16561, with greater upregulation in female subjects. The analysis
identified key miRNAs regulating gene expression in response to
recanalization, and NFE4 and MTF1 as crucial transcription factors
regulating these processes. Based on these data, a coregulatory network
underlying neutrophil activity was constructed, highlighting its central
role in early recanalization responses, especially in females.
Conclusions:
This study identified new genomic markers in blood
associated with recanalization, and identified critical age- and
sex-specific factors. By mapping a coregulatory network of interacting
genes and neutrophil-related pathways, the data provides insights to
inform future research and develop targeted therapies. Such therapies
can improve recanalization efficacy or modulate leukocytes to reduce
futile recanalization, ultimately enhancing clinical outcomes for
ischemic stroke patients.
Ischemic StrokeGene Expression
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