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Ann Clin Transl Neurol. 2019 Aug 10. doi: 10.1002/acn3.50861. [Epub ahead of print]

Blood transcriptomic biomarker as a surrogate of ischemic brain gene expression.

Author information

1
UMR 1078 Genetics, Functional Genomics and Biotechnology, Inserm, Université de Brest, EFS, CHU de Brest, Brest, France.
2
Department of Physiopathology and Imaging of Neurological Disorders, INSERM U1237, University Caen Normandie, GIP Cyceron, Caen, France.
3
GenoSplice Technology, iPEPS ICM, Hôpital Pitié Salpêtrière, Paris, France.
4
Inserm U1078, Université Bretagne Loire Université de Bretagne Occidentale, IBSAM, Laboratoire de Genetique Moleculaire et Histocompatibilité, CHRU de Brest, Hopital Morvan, Brest, France.
5
Neurology and Stroke Department, Centre Hospitalier Régional Universitaire (CHRU), Brest, France.
6
Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest, France.

Abstract

OBJECTIVES:

Blood biomarkers for cerebral tissue ischemia are lacking. The goal was to identify a blood transcriptomic signature jointly identified in the ischemic brain.

METHODS:

A nonhuman primate model with middle cerebral artery (MCA) territory infarction was used to study gene expression by microarray during acute ischemic cerebral stroke in the brain and the blood. Brain samples were collected in the infarcted and contralateral non-infarcted cortex as well as blood samples before and after occlusion. Gene expression was compared between the two brain locations to find differentially expressed genes. The expressions of these genes were then compared in the blood pre- and post-occlusion.

RESULTS:

Hierarchical clustering of brain expression data revealed strong independent clustering of ischemic and nonischemic brain samples. The top five enriched, up-regulated gene sets in the brain were TNF α signaling, apoptosis, P53 pathway, hypoxia, and UV response up. A comparison of differentially expressed genes in the brain and blood revealed a significant overlap of gene expression patterns. Stringent analysis of blood expression data from pre- and post-occlusion samples in each monkey identified nine genes highly differentially expressed in both the brain and the blood. Many of these up-regulated genes belong to pathways involved in cell death and DNA damage repair.

INTERPRETATION:

Common gene expression profile can be identified in the brain and blood and clearly differentiates ischemic from nonischemic conditions. Therefore, specific blood transcriptomic signature may represent a surrogate for brain ischemic gene expression.

PMID:
31400065
DOI:
10.1002/acn3.50861
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