Brain and Blood microRNA Expression Profiling of Ischemic Stroke, Intracerebral Hemorrhage, and Kainate Seizures

Liu, Da Zhi; Tian, Yingfang; Ander, Bradley P.; Xu, Huichun; Stamova, Boryana; Zhan, Xinhua; Turner, Renée J.; Jickling, Glen C.; Sharp, Frank R.

doi:10.1038/jcbfm.2009.186

Cited by 461 publications

(403 citation statements)

References 40 publications

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“…The explanation for this is unclear, but is certainly one indicator of the gender-dependent differences of the immune response to IS. One or several epigenetic mechanisms might lead to the observed differences including DNA methylation or histone deacetylation (both of which suppress gene expression), DNA sumoylation, and microRNAs that generally downregulate expression of their many targets (Dharap et al, 2009;Liu et al, 2010). Future studies will be required to determine whether there are genderspecific modifications of DNA methylation, histone deacetylation, and/or microRNA responses after stroke.…”

Section: Gender-specific Gene Expression At Different Timesmentioning

confidence: 99%

Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

Tian

Stamova

Jickling

et al. 2011

J Cereb Blood Flow Metab

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This study examined the effects of gender on RNA expression after ischemic stroke (IS). RNA obtained from blood of IS patients (n = 51; 153 samples at p3, 5, and 24 hours) and from matched controls (n = 52) were processed on Affymetrix microarrays. Analyses of covariance for stroke versus control samples were performed separately for both genders and the regulated genes for females compared with males. In all, 242, 227, and 338 male-specific genes were regulated at p3, 5, and 24 hours after IS, respectively, of which 59 were regulated at all time points. Overall, 774, 3,437, and 571 female-specific stroke genes were regulated at p3, 5, and 24 hours, respectively, of which 152 were regulated at all time points. Male-specific stroke genes were associated with integrin, integrin-liked kinase, actin, tight junction, Wnt/b-catenin, RhoA, fibroblast growth factors (FGF), granzyme, and tumor necrosis factor receptor (TNFR)2 signaling. Female-specific stroke genes were associated with p53, high-mobility group box-1, hypoxia inducible factor (HIF)1a, interleukin (IL)1, IL6, IL12, IL18, acute-phase response, T-helper, macrophage, and estrogen signaling. Cell death signaling was overrepresented in both genders, although the molecules and pathways differed. Gender affects gene expression in the blood of IS patients, which likely implies gender differences in immune, inflammatory, and cell death responses to stroke.

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Section: Gender-specific Gene Expression At Different Timesmentioning

confidence: 99%

Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

Tian

Stamova

Jickling

et al. 2011

J Cereb Blood Flow Metab

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“…Analysis of their results identified specific microRNAs that changed at least two-fold in response to these neuronal insults. Following ischemia, miR-182 was upregulated and miR-223 and miR-210 were downregulated in both blood and brain; in addition, four microRNAs (miR-29c, miR-34b-3p, miR-98, miR-122) were downregulated in both blood and brain after epilepsy (Liu et al, 2010). These data support the possibility that a subset of microRNAs may prove useful as biomarkers in that blood levels of these microRNAs correlate with their levels in the injured hippocampus.…”

Section: The Role Of Micrornas In Epilepsymentioning

confidence: 99%

“…If indeed altered levels of microRNAs are found to correlate with the severity of the disease, they could become valuable tools to diagnose this disease early and be able to administer treatment. There are several microRNAs that are altered in response to brain injury after stroke or seizures (Liu et al, 2010). In one study of young stroke patients, these profiles correlated with the type of stroke they suffered and the progress of recovery (Tan et al, 2009).…”

Section: Future Research Directionsmentioning

confidence: 99%

“…Preliminary studies in animal models of stroke and epilepsy indicate that specific microRNAs may serve as potential biomarkers for these neurological disorders (Liu et al, 2010). A recent study investigated microRNA expression profiles in the hippocampus and blood of animals 24 h after they were subjected to global ischemia or kainic acidinduced status epilepticus.…”

Section: The Role Of Micrornas In Epilepsymentioning

confidence: 99%

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Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

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“…1 Although miRs have been implicated in the pathophysiology of central nervous system (CNS) disorders [2][3][4] and may modulate neuronal cell death pathways, 5 few have been directly evaluated at a mechanistic level in traumatic brain injury (TBI). 6,7 TBI initiates regulated neuronal death mechanisms that significantly contribute to neuronal loss and neurological dysfunction.…”

mentioning

confidence: 99%

miR-711 upregulation induces neuronal cell death after traumatic brain injury

et al. 2015

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Traumatic brain injury (TBI) is a leading cause of mortality and disability. MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression at post-transcriptional level and may be key modulators of neuronal apoptosis, yet their role in secondary injury after TBI remains largely unexplored. Changes in miRs after controlled cortical impact (CCI) in mice were examined during the first 72 h using miR arrays and qPCR. One selected miR (711) was examined with regard to its regulation and relation to cell death; effects of miR-711 modulation were evaluated after CCI and using in vitro cell death models of primary cortical neurons. Levels of miR-711 were increased in the cortex early after TBI and in vitro models through rapid upregulation of miR-711 transcription (pri-miR-711) rather than catabolism. Increases coincided with downregulation of the pro-survival protein Akt, a predicted target of miR-711, with sequential activation of forkhead box O3 (FoxO3)a/glycogen synthase kinase 3 (GSK3)α/β, pro-apoptotic BH3-only molecules PUMA (Bcl2-binding component 3) and Bim (Bcl2-like 11 (apoptosis facilitator)), and mitochondrial release of cytochrome c and AIF. miR-711 and Akt (mRNA) co-immunoprecipitated with the RNA-induced silencing complex (RISC). A miR-711 hairpin inhibitor attenuated the apoptotic mechanisms and decreased neuronal death in an Aktdependent manner. Conversely, a miR-711 mimic enhanced neuronal apoptosis. Central administration of the miR-711 hairpin inhibitor after TBI increased Akt expression and attenuated apoptotic pathways. Treatment reduced cortical lesion volume, neuronal cell loss in cortex and hippocampus, and long-term neurological dysfunction. miR-711 changes contribute to neuronal cell death after TBI, in part by inhibiting Akt, and may serve as a novel therapeutic target.

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Brain and Blood microRNA Expression Profiling of Ischemic Stroke, Intracerebral Hemorrhage, and Kainate Seizures

Cited by 461 publications

References 40 publications

Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

Epigenetic Mechanisms in Stroke and Epilepsy

miR-711 upregulation induces neuronal cell death after traumatic brain injury

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