Gene expression profiles of patients with cerebral hematoma following spontaneous intracerebral hemorrhage

Yang,Tao; Gu,Jianwen; Kong,Bin; Kuang,Yongqin; Cheng,Lin; Cheng,Jingmin; Xia,Xun; Ma,Yuan; Zhang,Junhai

doi:10.3892/mmr.2014.2421

Gene expression profiles of patients with cerebral hematoma following spontaneous intracerebral hemorrhage

Authors:
- Tao Yang
- Jianwen Gu
- Bin Kong
- Yongqin Kuang
- Lin Cheng
- Jingmin Cheng
- Xun Xia
- Yuan Ma
- Junhai Zhang
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Affiliations: Department of Neurosurgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China
Published online on: July 25, 2014 https://doi.org/10.3892/mmr.2014.2421
Pages: 1671-1678
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The present study aimed to investigate the gene functions and expression profiles in perihematomal (PH) brain regions following spontaneous intracerebral hemorrhage. The gene expression profiles were downloaded from the Gene Expression Omnibus database under accession number GSE24265, which includes 11 brain samples from different regions, including four samples from PH areas, four from contralateral grey matter (CG) and three from contralateral white matter (CW). The gene expression profiles were pre-processed and the differentially expressed genes (DEGs) between PH and CG tissue, and PH and CW tissue were identified using R packages. The expression of genes in different tissues was analyzed by hierarchical clustering. Then, the interaction network between the DEGs was constructed using String software. Finally, Gene Ontology was performed and pathway analysis was conducted using FuncAssociate and Expression Analysis Systematic Explorer to identify the gene function. As a result, 399 DEGs were obtained between PH and CG, and 756 DEGs were identified between PH and CW. There were 35 common DEGs between the two groups. These DEGs may be involved in PH edema by regulating the calcium signaling pathway [calcium channel, voltage‑dependent, T-type, α1I subunit, Ca2+/calmodulin‑dependent protein kinase II α (CAMK2A), ryanodine receptor 2 (RYR2) and inositol 1,4,5-trisphosphate receptor, type 1 (ITPR1)], cell proliferation (sphingosine kinase 1), neuron differentiation (Ephrin-A5) or extracellular matrix-receptor interaction [collagen, type I, α 2, laminin B1 (LAMB1), syndecan 2, fibronectin 1 and integrin α5 (ITGA5)]. A number of genes may cooperate to participate in the same pathway, such as ITPR1-RYR2, CAMK2A-RYR2 and ITGA5-LAMB1 interaction pairs. The present study provides several potential targets to decrease hematoma expansion and alleviate neuronal cell death following spontaneous intracerebral hemorrhage.

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1	Aguilar MI and Freeman WD: Spontaneous intracerebral hemorrhage. Semin Neurol. 30:555–564. 2010. View Article : Google Scholar
2	Thiex R and Tsirka SE: Brain edema after intracerebral hemorrhage: mechanisms, treatment options, management strategies, and operative indications. Neurosurg Focus. 22:E62007. View Article : Google Scholar
3	Wang J and Doré S: Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 27:894–908. 2006.
4	Hua Y, Keep RF, Hoff JT and Xi G: Brain injury after intracerebral hemorrhage: the role of thrombin and iron. Stroke. 38(Suppl): 759–762. 2007. View Article : Google Scholar : PubMed/NCBI
5	Xi G, Keep RF and Hoff JT: Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 5:53–63. 2006. View Article : Google Scholar : PubMed/NCBI
6	Aronowski J and Zhao X: Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 42:1781–1786. 2011. View Article : Google Scholar : PubMed/NCBI
7	Tuhrim S, Horowitz DR, Sacher M and Godbold JH: Validation and comparison of models predicting survival following intracerebral hemorrhage. Crit Care Med. 23:950–954. 1995. View Article : Google Scholar : PubMed/NCBI
8	Xi G and Hoff J: The pathophysiology of hemorrhagic lesions. Imaging of the Nervous System: Diagnosis and Therapeutic Applications. Latchaw R, Kucharczyk J and Moseley ME: 1 and 2. Elsevier Mosby; Philadelphia: pp. 519–534. 2005
9	Brown DL and Morgenstern LB: Stopping the bleeding in intracerebral hemorrhage. N Engl J Med. 352:828–830. 2005. View Article : Google Scholar : PubMed/NCBI
10	Ohnishi M, Monda A, Takemoto R, et al: Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage. Neuroscience. 232C:45–52. 2012.
11	Hu YY, Huang M, Dong XQ, Xu QP, Yu WH and Zhang ZY: Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: Possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway. J Ethnopharmacol. 137:1462–1468. 2011. View Article : Google Scholar : PubMed/NCBI
12	Carmichael ST, Vespa PM, Saver JL, et al: Genomic profiles of damage and protection in human intracerebral hemorrhage. J Cereb Blood Flow Metab. 28:1860–1875. 2008. View Article : Google Scholar : PubMed/NCBI
13	Rosell A, Vilalta A, García-Berrocoso T, et al: Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage. PLoS One. 6:e167502011. View Article : Google Scholar
14	Troyanskaya O, Cantor M, Sherlock G, et al: Missing value estimation methods for DNA microarrays. Bioinformatics. 17:520–525. 2001. View Article : Google Scholar : PubMed/NCBI
15	Fujita A, Sato JR, de Rodrigues LO, Ferreira CE and Sogayar MC: Evaluating different methods of microarray data normalization. BMC Bioinformatics. 7:4692006. View Article : Google Scholar : PubMed/NCBI
16	Wettenhall JM and Smyth GK: limmaGUI: a graphical user interface for linear modeling of microarray data. Bioinformatics. 20:3705–3706. 2004. View Article : Google Scholar : PubMed/NCBI
17	Benjamini Y and Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 57:289–300. 1995.
18	Liu CL, Prapong W, Natkunam Y, et al: Software tools for high-throughput analysis and archiving of immunohistochemistry staining data obtained with tissue microarrays. Am J Pathol. 161:1557–1565. 2002. View Article : Google Scholar
19	Giot L, Bader JS, Brouwer C, et al: A protein interaction map of Drosophila melanogaster. Science. 302:1727–1736. 2003. View Article : Google Scholar : PubMed/NCBI
20	Li S, Armstrong CM, Bertin N, et al: A map of the interactome network of the metazoan C. elegans. Science. 303:540–543. 2004. View Article : Google Scholar : PubMed/NCBI
21	Szklarczyk D, Franceschini A, Kuhn M, et al: The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39:D561–D568. 2011. View Article : Google Scholar : PubMed/NCBI
22	Berriz GF, Beaver JE, Cenik C, Tasan M and Roth FP: Next generation software for functional trend analysis. Bioinformatics. 25:3043–3044. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hosack DA, Dennis G Jr, Sherman BT, Lane HC and Lempicki RA: Identifying biological themes within lists of genes with EASE. Genome Biol. 4:R702003. View Article : Google Scholar : PubMed/NCBI
24	Kahle KT, Simard JM, Staley KJ, Nahed BV, Jones PS and Sun D: Molecular mechanisms of ischemic cerebral edema: role of electroneutral ion transport. Physiology (Bethesda). 24:257–265. 2009. View Article : Google Scholar : PubMed/NCBI
25	Bodalia A, Li H and Jackson MF: Loss of endoplasmic reticulum Ca²⁺homeostasis: contribution to neuronal cell death during cerebral ischemia. Acta Pharmacol Sin. 34:49–59. 2013.
26	Kakizawa S, Yamazawa T, Chen Y, et al: Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. EMBO J. 31:417–428. 2012. View Article : Google Scholar : PubMed/NCBI
27	Liao Y, Kristiansen A-M, Oksvold CP, et al: Neuronal Ca²⁺-activated K⁺ channels limit brain infarction and promote survival. PLoS One. 5:e156012010.PubMed/NCBI
28	McGeown JG: Interactions between inositol 1, 4, 5-trisphosphate receptors and ryanodine receptors in smooth muscle: one store or two? Cell Calcium. 35:613–619. 2004. View Article : Google Scholar : PubMed/NCBI
29	Maxwell JT, Natesan S and Mignery GA: Modulation of inositol 1, 4, 5-trisphosphate receptor type-2 channel activity by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation. J Biol Chem. 287:39419–39428. 2012. View Article : Google Scholar : PubMed/NCBI
30	Dev KK, Mullershausen F, Mattes H, et al: Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis. Pharmacol Ther. 117:77–93. 2008. View Article : Google Scholar : PubMed/NCBI
31	Pébay A, Toutant M, Prémont J, et al: Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades. Eur J Neurosci. 13:2067–2076. 2001.PubMed/NCBI
32	McVerry BJ and Garcia JG: In vitro and in vivo modulation of vascular barrier integrity by sphingosine 1-phosphate: mechanistic insights. Cell Signal. 17:131–139. 2005. View Article : Google Scholar : PubMed/NCBI
33	Altay O, Hasegawa Y, Sherchan P, et al: Isoflurane delays the development of early brain injury after subarachnoid hemorrhage through sphingosine-related pathway activation in mice. Crit Care Med. 40:1908–1913. 2012. View Article : Google Scholar
34	Overman JJ, Clarkson AN, Wanner IB, et al: A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke. Proc Natl Acad Sci USA. 109:E2230–E2239. 2012. View Article : Google Scholar : PubMed/NCBI
35	Sobel RA: Ephrin A receptors and ligands in lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol. 15:35–45. 2005. View Article : Google Scholar : PubMed/NCBI
36	Bodmer D, Vaughan KA, Zacharia BE, Hickman ZL and Connolly ES: The molecular mechanisms that promote edema after intracerebral hemorrhage. Transl Stroke Res. 3(Suppl 1): 52–61. 2012. View Article : Google Scholar : PubMed/NCBI
37	Baeten KM and Akassoglou K: Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke. Dev Neurobiol. 71:1018–1039. 2011. View Article : Google Scholar : PubMed/NCBI
38	Abbott NJ, Patabendige AA, Dolman DE, Yusof SR and Begley DJ: Structure and function of the blood-brain barrier. Neurobiol Dis. 37:13–25. 2010. View Article : Google Scholar