TY - JOUR
T1 - The acute phase serum zinc concentration is a reliable biomarker for predicting the functional outcome after spinal cord injury
AU - Kijima, Ken
AU - Kubota, Kensuke
AU - Hara, Masamitsu
AU - Kobayakawa, Kazu
AU - Yokota, Kazuya
AU - Saito, Takeyuki
AU - Yoshizaki, Shingo
AU - Maeda, Takeshi
AU - Konno, Daijiro
AU - Matsumoto, Yoshihiro
AU - Nakashima, Yasuharu
AU - Okada, Seiji
N1 - Funding Information:
This study was supported by JSPS KAKENHI Grant Number JP18K16680 (K.K.); a Grant-in-Aid for Scientific Research (B) ( 16H05450 ) (S.O.); Challenging Exploratory Research from the Ministry of Education, Science, and Sports ( 16K15668 ) (S.O.); AMED under Grant Number 19gm6210003h0002 (S.O.); and research foundations from the general insurance association of Japan (K.K.). The funders had no role in the study design, data collection, data analysis, interpretation, writing of the report.
Publisher Copyright:
© 2019 The Authors
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ebiom.2019.03.003
DO - 10.1016/j.ebiom.2019.03.003
M3 - Article
C2 - 30902739
AN - SCOPUS:85063040232
SN - 2352-3964
VL - 41
SP - 659
EP - 669
JO - EBioMedicine
JF - EBioMedicine
ER -