Ischemic transient neurological events identified by immune response to cerebral ischemia

Glen C. Jickling, Xinhua Zhan, Boryana Stamova, Bradley Ander, Yingfang Tian, Da Liu, Shara Mae Sison, Piero Verro, S. Claiborne Johnston, Frank R Sharp

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.

Original languageEnglish (US)
Pages (from-to)1006-1012
Number of pages7
JournalStroke
Volume43
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Brain Ischemia
Transient Ischemic Attack
Stroke
Ischemia
Genes
Immune System
RNA
Genetic Association Studies
Granulocytes
B-Lymphocytes
Sensitivity and Specificity

Keywords

  • gene expression
  • immune response
  • ischemia
  • ischemic stroke
  • TIA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Ischemic transient neurological events identified by immune response to cerebral ischemia. / Jickling, Glen C.; Zhan, Xinhua; Stamova, Boryana; Ander, Bradley; Tian, Yingfang; Liu, Da; Sison, Shara Mae; Verro, Piero; Johnston, S. Claiborne; Sharp, Frank R.

In: Stroke, Vol. 43, No. 4, 04.2012, p. 1006-1012.

Research output: Contribution to journalArticle

Jickling, Glen C. ; Zhan, Xinhua ; Stamova, Boryana ; Ander, Bradley ; Tian, Yingfang ; Liu, Da ; Sison, Shara Mae ; Verro, Piero ; Johnston, S. Claiborne ; Sharp, Frank R. / Ischemic transient neurological events identified by immune response to cerebral ischemia. In: Stroke. 2012 ; Vol. 43, No. 4. pp. 1006-1012.
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T1 - Ischemic transient neurological events identified by immune response to cerebral ischemia

AU - Jickling, Glen C.

AU - Zhan, Xinhua

AU - Stamova, Boryana

AU - Ander, Bradley

AU - Tian, Yingfang

AU - Liu, Da

AU - Sison, Shara Mae

AU - Verro, Piero

AU - Johnston, S. Claiborne

AU - Sharp, Frank R

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N2 - Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.

AB - Background and Purpose-Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. Methods-Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change ≥1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). Results-Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD scores. Conclusions-A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated.

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KW - ischemia

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KW - TIA

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