- •miRNA differentiate SAH complications such as delayed cerebral infarction.
- •Early Brain Injury restructures miRNA expression in cerebrospinal fluid.
- •miRNA fingerprints reflect blood-brain barrier instability, autophagy and apoptosis.
- •miRNA in SAH and ischemic stroke overlap and highlight shared pathophysiology.
Subarachnoid hemorrhage (SAH) is fatal and detrimental to quality of life.
Clinically, options for monitoring are often limited, potentially missing subtle neurological changes especially in low-grade patients. This article reviewed miRNA dysregulation in SAH and analyzed their functional and clinical relevance.
With adherence to PRISMA guideline, PubMed, EMBASE, GEO and ArrayExpress were searched comprehensively for relevant clinical and animal models. Datasets were analyzed and enriched by experimentally validated targets and multiple databases using R v3.4.2, Ingenuity Pathway Analysis, and miRPath v3.0.
Among 1926 search results, 18 studies were screened for full-text assessment. The 8 included studies revealed a marked miRNA dysregulation after SAH. 2 datasets were retrieved. In both serum and CSF, different miRNA profiles were associated with Early Brain Injury, Delayed Cerebral Infarction, vasospasm and prognosis. In CSF, a dramatic restructure of inter-miRNA correlation matrix was observed. Enrichment analysis revealed strong association (1) BBB instability, with adherens, extra-cellular matrix, actin cytoskeleton, integrin, TGF-β, Wnt/β-catenin etc; (2) autophagy, with MTORC1, HIF-1, ULK2, and FoxO etc; (3) apoptosis, with PI3K-Akt, p53, and AMPK. We analyzed common miRNAs across SAH and cerebral ischemia. They were related to neuronal differentiation, oxidation stress, apoptosis, angiogenesis, Alzheimer’s disease, NMDA-induced calcium influx, excitotoxicity and NO production.
Clinical progression of SAH is associated with different miRNA fingerprints. They carry neuro-pathological relevance and can be a potential biomarker which compliments SAH management.
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- Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.Lancet Neurol. 2009; 8: 355-369https://doi.org/10.1016/S1474-4422(09)70025-0
- Cognitive domain deficits in patients with aneurysmal subarachnoid haemorrhage at 1 year.J Neurol Neurosurg Psychiatry. 2013; 84: 1054-1058https://doi.org/10.1136/jnnp-2012-304517
- Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage.Stroke. 2010; 41: e519-e536https://doi.org/10.1161/STROKEAHA.110.581975
- Stroke in women: risk factors and clinical biomarkers.J Cell Biochem. 2017; 118: 4191-4202https://doi.org/10.1002/jcb.26130
- The importance of early brain injury after subarachnoid hemorrhage.Prog Neurobiol. 2012; 97: 14-37https://doi.org/10.1016/j.pneurobio.2012.02.003
- Spontaneous subarachnoid haemorrhage.Lancet. 2017; 389: 655-666https://doi.org/10.1016/S0140-6736(16)30668-7
- Biomarkers as outcome predictors in subarachnoid hemorrhage – a systematic review.Biomarkers. 2014; 19: 95-108https://doi.org/10.3109/1354750X.2014.881418
- MicroRNA biogenesis pathways in cancer.Nat Rev Cancer. 2015; 15: 321-333https://doi.org/10.1038/nrc3932
- MicroRNA-204/211 alters epithelial physiology.FASEB J. 2010; 24: 1552-1571https://doi.org/10.1096/fj.08-125856
- A set of differentially expressed miRNAs, including miR-30a-5p, act as post-transcriptional inhibitors of BDNF in prefrontal cortex.Hum Mol Genet. 2008; 17: 3030-3042https://doi.org/10.1093/hmg/ddn201
- Neuroprotective effects of p53/microRNA‑22 regulate inflammation and apoptosis in subarachnoid hemorrhage.Int J Mol Med. 2018; https://doi.org/10.3892/ijmm.2018.3392
- Emerging roles of microRNAs in ischemic stroke: as possible therapeutic agents.J Stroke. 2017; 19: 166-187https://doi.org/10.5853/jos.2016.01368
- Alteration of the microRNA network during the progression of Alzheimer’s disease: Profiling of microRNAs in Alzheimer’s disease.EMBO Mol Med. 2013; 5: 1613-1634https://doi.org/10.1002/emmm.201201974
- Circulating miRNAs as biomarkers for neurodegenerative disorders.Molecules. 2014; 19: 6891-6910https://doi.org/10.3390/molecules19056891
- Circulating microRNAs serve as novel biological markers for intracranial aneurysms.J Am Heart Assoc. 2014; 3e000972https://doi.org/10.1161/JAHA.114.000972
- Circulating microRNAs in patients with intracranial aneurysms.PLoS One. 2017; 12e0176558https://doi.org/10.1371/journal.pone.0176558
- Toward understanding non-coding RNA roles in intracranial aneurysms and subarachnoid hemorrhage.Transl Neurosci. 2017; 8: 54-64https://doi.org/10.1515/tnsci-2017-0010
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097https://doi.org/10.1371/journal.pmed.1000097
Revelle WR, psych: Procedures for Personality and Psychological Research; 2017.
- DIANA-TarBase v7. 0: indexing more than half a million experimentally supported miRNA:mRNA interactions.Nucleic Acids Res. 2015; 43: D153-D159https://doi.org/10.1093/nar/gku1215
- DIANA-miRPath v3. 0: deciphering microRNA function with experimental support.Nucleic Acids Res. 2015; 43: W460-W466https://doi.org/10.1093/nar/gkv403
- Predicting effective microRNA target sites in mammalian mRNAs.eLife. 2015; 4https://doi.org/10.7554/eLife.05005
- Circulating MicroRNAs in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.J Am Heart Assoc. 2017; 6https://doi.org/10.1161/JAHA.116.005363
- MicroRNA changes in cerebrospinal fluid after subarachnoid hemorrhage.Stroke. 2017; https://doi.org/10.1161/STROKEAHA.117.017804
- Role of autophagy in early brain injury after experimental subarachnoid hemorrhage.J Mol Neurosci. 2012; 46: 192-202https://doi.org/10.1007/s12031-011-9575-6
- Decorin alleviated chronic hydrocephalus via inhibiting TGF-β1/Smad/CTGF pathway after subarachnoid hemorrhage in rats.Brain Res. 2016; 1630: 241-253https://doi.org/10.1016/j.brainres.2015.11.004
- Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer.Nat Rev Cancer. 2003; 3: 807-820https://doi.org/10.1038/nrc1208
- TGF-β/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos.PLoS One. 2013; 8e55186https://doi.org/10.1371/journal.pone.0055186
- Serum and cerebrospinal fluid concentrations of E-selectin in patients with aneurysmal subarachnoid hemorrhage.Braz J Med Biol Res. 2005; 38 (S0100-879X2005001100020): 1703-1710
- Integrin signaling.Science. 1999; 285: 1028-1033https://doi.org/10.1126/science.285.5430.1028
- The Wnt /β-catenin signaling pathway in the adult neurogenesis: the Wnt /β-catenin signaling pathway.Eur J Neurosci. 2011; 33: 1-8https://doi.org/10.1111/j.1460-9568.2010.7483.x
- Survivin, a key component of the Wnt/β-catenin signaling pathway, contributes to traumatic brain injury-induced adult neurogenesis in the mouse dentate gyrus.Int J Mol Med. 2013; 32: 867-875https://doi.org/10.3892/ijmm.2013.1456
- Apoptotic Mechanisms for Neuronal Cells in Early Brain Injury After Subarachnoid Hemorrhage.in: Feng H. Mao Y. Zhang J.H. Early Brain Injury or Cerebral Vasospasm. Springer Vienna, Vienna2011: 43-48https://doi.org/10.1007/978-3-7091-0353-1_8
- FoxO proteins in the nervous system.Anal Cell Pathol. 2015; 2015: 1-15https://doi.org/10.1155/2015/569392
- MicroRNA-223 is neuroprotective by targeting glutamate receptors.Proc Natl Acad Sci. 2012; 109: 18962-18967https://doi.org/10.1073/pnas.1121288109
- MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain.Gene Ther. 2014; 21: 37-43https://doi.org/10.1038/gt.2013.55
- miRNA expression profiling of cerebrospinal fluid in patients with aneurysmal subarachnoid hemorrhage.J Neurosurg. 2017; 126: 1131-1139https://doi.org/10.3171/2016.1.JNS151454
- Human cerebrospinal fluid microRNA: temporal changes following subarachnoid hemorrhage.Physiol Genomics. 2016; 48: 361-366https://doi.org/10.1152/physiolgenomics.00052.2015
- Regulation of microRNAs miR-30a and miR-143 in cerebral vasculature after experimental subarachnoid hemorrhage in rats.BMC Genomics. 2015; 16: 119https://doi.org/10.1186/s12864-015-1341-7
- Long non-coding RNA and microRNA-675/let-7a mediates the protective effect of melatonin against early brain injury after subarachnoid hemorrhage via targeting TP53 and neural growth factor.Cell Death Dis. 2018; 9https://doi.org/10.1038/s41419-017-0155-8
Published online: November 24, 2018
Accepted: November 10, 2018
Received: September 22, 2018
© 2018 Elsevier Ltd. All rights reserved.