The Critical Role of Erythrolysis and Microglia/Macrophages in Clot Resolution After Intracerebral Hemorrhage: A Review of the Mechanisms and Potential Therapeutic Targets

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

Translational Stroke Research ◽

10.1007/s12975-016-0477-3 ◽

2016 ◽

Vol 7 (5) ◽

pp. 420-438 ◽

Cited By ~ 25

Author(s):

Na Sun ◽

Richard F. Keep ◽

Ya Hua ◽

Guohua Xi

Keyword(s):

Critical Role ◽

Therapeutic Targets ◽

Current Utility

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Abstract TP327: Major Inflammatory Pathways in Peripheral Blood Associate With Intracerebral Hemorrhage Volume in Human

Stroke ◽

10.1161/str.51.suppl_1.tp327 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Marc Durocher ◽

Bradley Ander ◽

Alan Yee ◽

Glen Jickling ◽

Kwan Ng ◽

...

Keyword(s):

Gene Expression ◽

Intracerebral Hemorrhage ◽

Peripheral Blood ◽

Critical Role ◽

Therapeutic Targets ◽

Fc Receptor ◽

Whole Genome ◽

Blood Draw ◽

Inflammatory Pathways ◽

Pathway Activation

Objectives: Intracerebral hemorrhage (ICH) volume is a major determinant of functional outcome. The peripheral immune system plays a critical role in post-ICH damage and repair. Identifying potential modulators of ICH volume may guide the search for therapeutic targets. We performed a whole genome expression study in peripheral blood to examine the immune response following ICH with respect to ICH volume. Methods: Whole-genome RNA expression from 18 ICH subjects (14M/4F) was assessed on Affymetrix HTA 2.0 microarrays. Volumetric measurements were conducted on CT images using AnalyzePro. Multiple Regression including ICH volume while accounting for time from ICH onset to blood draw and interval between scan time and blood draw, was performed. A partial correlation between gene expression and ICH volume was calculated, with FDR p<0.3 (nominal p<0.005) and Pearson Correlation coefficient r>|0.6| considered significant. Pathway analysis and activation/suppression prediction of over-represented pathways was performed (Benjamini-Hochberg p<0.05, pathway activation/suppression Z-score >|2|). Results: Gene expression levels of 281 genes, including coding (mRNA) and non-coding RNA (i.e. several miRNAs) were associated with ICH volume. Major pathways, such as Neuroinflammation Signaling, were predicted to be activated in subjects with larger ICH volumes. So were Inflammasome Pathway, Toll-like Receptor, Leukocyte Extravasation, NF-kB signaling and FC? Receptor-Mediated Phagocytosis – some of which have been associated with poor clinical outcomes. Scavenger mechanisms, such as FC? Receptor-Mediated Phagocytosis, have been implicated in hematoma resolution. Thrombin Signaling, involved in coagulation, was also activated in subjects with larger ICH volumes. Peroxisome Proliferator-Activated Receptor (PPAR) Signaling was predicted to be suppressed in subjects with larger ICH volumes. PPAR pathway activation may have a neuroprotective effect following experimental ICH. Conclusions: We provide human data on genes and pathways associated with ICH volume. The results reveal major inflammatory pathways associated with ICH volume, which may be therapeutic targets for human ICH.

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The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

Perspectives on Language Learning and Education ◽

10.1044/lle15.2.50 ◽

2008 ◽

Vol 15 (2) ◽

pp. 50-59 ◽

Cited By ~ 1

Author(s):

Amy Philofsky

Keyword(s):

Language Development ◽

Critical Role ◽

Children With Autism ◽

Autism Spectrum ◽

Children With Asd ◽

Prevalence Estimates ◽

Notable Increase ◽

Screening Assessment ◽

Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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