Ischemic transient neurological events identified by immune response to cerebral ischemia.
OBJECTIVE
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(2) 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.
University of California at Davis, MIND Institute, 2805 50th Street, Sacramento, CA 95817, USA. gcjickling@ucdavis.edu
Glen C
GC
Jickling
Xinhua
X
Zhan
Boryana
B
Stamova
Bradley P
BP
Ander
Yingfang
Y
Tian
Dazhi
D
Liu
Shara-Mae
SM
Sison
Piero
P
Verro
S Claiborne
SC
Johnston
Frank R
FR
Sharp
D056704:Adaptive Immunity; D000368:Aged; D002545:Brain Ischemia / Q000097:blood / Q000150:complications / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology; D012313:RNA / Q000097:blood / Q000276:immunology; D020521:Stroke / Q000097:blood / Q000150:complications / Q000276:immunology
D012313:RNA