Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke

Madoka Yoshida; Naoki Kato; Takeshi Uemura; Mutsumi Mizoi; Mizuho Nakamura; Ryotaro Saiki; Keisuke Hatano; Kunitomo Sato; Shota Kakizaki; Aya Nakamura; Takuya Ishii; Tohru Terao; Yuichi Murayama; Keiko Kashiwagi; Kazuei Igarashi

doi:10.1016/j.ensci.2017.03.005

Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke

eNeurologicalSci. 2017 Mar 30:7:18-24. doi: 10.1016/j.ensci.2017.03.005. eCollection 2017 Jun.

Authors

Madoka Yoshida¹, Naoki Kato^{2

3}, Takeshi Uemura¹, Mutsumi Mizoi¹, Mizuho Nakamura¹, Ryotaro Saiki¹, Keisuke Hatano^{2

3}, Kunitomo Sato^{2

3}, Shota Kakizaki^{2

3}, Aya Nakamura^{2

3}, Takuya Ishii^{2

3}, Tohru Terao^{2

3}, Yuichi Murayama³, Keiko Kashiwagi⁴, Kazuei Igarashi^{1

5}

Affiliations

¹ Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Chiba, Japan.
² Department of Neurosurgery, Atsugi Municipal Hospital, Atsugi, Kanagawa, Japan.
³ Department of Neurosurgery, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
⁴ Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
⁵ Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Chiba, Japan.

Abstract

Objective: Measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to determine how these biomarkers vary during stroke.

Methods: Levels of PC-Acro, IL-6 and CRP in plasma were measured on day 0, 2, 7 and 14 after the onset of ischemic or hemorrhagic stroke.

Results: After the onset of stroke, the level of PC-Acro in plasma was elevated corresponding to the size of stroke. It returned to near control levels by day 2, and remained similar through day 14. The degree of the decrease in PC-Acro on day 2 was greater when the size of brain infarction or hemorrhage was larger. An increase in IL-6 and CRP occurred after the increase in PC-Acro, and it was well correlated with the size of the injury following infarction or hemorrhage. The results suggest that acrolein becomes a trigger for the production of IL-6 and CRP, as previously observed in a mouse model of stroke and in cell culture systems. The increase in IL-6 and CRP was also correlated with poor outcome judging from mRS.

Conclusion: The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

Keywords: Biomarkers; Brain hemorrhage; Brain infarction; C-reactive protein; CRP, C-reactive protein; IL-6, interleukin-6; Interleukin-6; NIHSS, NIH stroke scale; PC-Acro, protein-conjugated acrolein; Protein-conjugated acrolein (PC-Acro); SBI, silent brain infarction; WMH, white matter hyperintensity; mRS, modified Rankin Scale.