The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury

Ken Kijima, Kensuke Kubota, Masamitsu Hara, Kazu Kobayakawa, Kazuya Yokota, Takeyuki Saito, Shingo Yoshizaki, Takeshi Maeda, Daijiro Konno, Yoshihiro Matsumoto, Yasuharu Nakashima, Seiji Okada

Research output: Contribution to journalArticle

Abstract

Background: Spinal cord injury (SCI) is a devastating disorder for which the accurate prediction of the functional prognosis is urgently needed. Due to the lack of reliable prediction methods, the acute evaluation of SCI severity and therapeutic intervention efficacy is extremely difficult, presenting major obstacles to the development of acute SCI treatment. We herein report a novel method for accurately predicting the functional prognosis using the acute-phase serum zinc concentration after SCI. Methods: We produced experimental animal SCI models with different prognoses and examined the relationship among the SCI severity, functional outcome, and acute-phase serum zinc concentration. We also examined whether we could predict the functional prognosis by evaluating the serum zinc concentration within 72 h after SCI in a human prospective study. Findings: In a mouse model, the acute serum zinc concentrations decreased in proportion to SCI severity and the serum zinc concentrations at 12 h after SCI accurately predicted the functional prognosis. We clarified the mechanism underlying this serum zinc proportional decrease, showing that activated monocytes took up zinc from blood-serum and then infiltrated the lesion area in a severity-dependent manner. A non-linear regression analysis of 38 SCI patients showed that the serum zinc concentrations in the acute-phase accurately predicted the long-term functional outcome (R 2 = 0·84) more accurately than any other previously reported acute-phase biomarkers. Interpretation: The acute-phase serum zinc concentration could be a useful biomarker for predicting the functional prognosis. This simple method will allow for more objective clinical trials and the development of patient-tailored treatment for SCI.

Original languageEnglish
Pages (from-to)659-669
Number of pages11
JournalEBioMedicine
Volume41
DOIs
Publication statusPublished - Mar 1 2019

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Biomarkers
Spinal Cord Injuries
Zinc
Serum
Patient treatment
Regression analysis
Monocytes
Animals
Blood
Therapeutics
Regression Analysis
Clinical Trials
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury. / Kijima, Ken; Kubota, Kensuke; Hara, Masamitsu; Kobayakawa, Kazu; Yokota, Kazuya; Saito, Takeyuki; Yoshizaki, Shingo; Maeda, Takeshi; Konno, Daijiro; Matsumoto, Yoshihiro; Nakashima, Yasuharu; Okada, Seiji.

In: EBioMedicine, Vol. 41, 01.03.2019, p. 659-669.

Research output: Contribution to journalArticle

Kijima, Ken ; Kubota, Kensuke ; Hara, Masamitsu ; Kobayakawa, Kazu ; Yokota, Kazuya ; Saito, Takeyuki ; Yoshizaki, Shingo ; Maeda, Takeshi ; Konno, Daijiro ; Matsumoto, Yoshihiro ; Nakashima, Yasuharu ; Okada, Seiji. / The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury. In: EBioMedicine. 2019 ; Vol. 41. pp. 659-669.
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AU - Yokota, Kazuya

AU - Saito, Takeyuki

AU - Yoshizaki, Shingo

AU - Maeda, Takeshi

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