Neurological Sciences

, Volume 39, Issue 6, pp 1093–1104 | Cite as

Thrombomodulin, alarmin signaling, and copeptin: cross-talk between obesity and acute ischemic stroke initiation and severity in Egyptians

  • Walaa A. Keshk
  • Doaa H. Zineldeen
  • Yasser A. El-heneedy
  • Azza A. Ghali
Original Article


Acute ischemic stroke (AIS) is followed by a strong inflammatory response contributing to brain damage and making early diagnosis and treatment inevitable. Hence, obesity is a state of chronic inflammation with amplified oxidative stress; this study aimed to assess the role played by thrombomodulin (TM)/alarmin signaling pathway and copeptin in AIS initiation and severity in addition to the implication of abnormal body weight. The study was conducted on 50 participants; 30 were patients with AIS (15 overweight/obese and 15 normal weight), 10 were overweight/obese, and 10 were normal weight. Plasma TM, copeptin, high mobility group box1 (HMGB1), and lipocalin 2 (LCN2) levels were immunoassayed. Toll-like receptor 4 (TLR4) mRNA expression was evaluated by real-time PCR, National Institutes of Health Stroke Scale (NIHSS), carotid intima media thickness; atherogenic index and glycemic status were also assessed. TM, copeptin, HMGB1, and LCN2 levels were significantly increased in overweight/obese AIS patients and in AIS patients with NIHSS score ≥ 7 when compared to other groups (p value=, ˂ 0.001*). Receiver operating characteristic (ROC) curve elaborated HMGB-1 and LCN2 as the best biomarker for diagnosis and prediction of AIS severity, respectively. Regression analysis avails LCN2 and TM as best biomarker for AIS severity predication. In conclusion, these results highlighted detrimental role of alarmin signaling with increased adaptive response to block this pathway through TM in addition to increased copeptin level as an acute damage marker and their tight relation to WC not to BMI in AIS which clarify the implication of central adiposity.


Acute ischemic stroke (AIS) NIHSS score Carotid intima media thickness (CIMT) Thrombomodulin High mobility group box-1 (HMGB1) Lipocalin 2 (LCN) Toll-like receptor-4 (TLR4) 



We would like to thank Dr. Zaytoun H. (Radiology Department, Tanta University) for the radiological examinations.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The Ethical Committee of Tanta Faculty of Medicine approved this study (31649).

Supplementary material

10072_2018_3396_MOESM1_ESM.docx (295 kb)
ESM 1 (DOCX 295 kb)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Biochemistry & Molecular Biology, Faculty of MedicineTanta UniversityTantaEgypt
  2. 2.Department of Neuropsychiatry, Faculty of MedicineTanta UniversityTantaEgypt

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