重症外傷性脳損傷の転帰予測因子としての脳脊髄液中のアポトーシス．観察的研究

Apoptosis in cerebrospinal fluid as outcome predictors in severe traumatic brain injury: An observational study.

• Wenqing Jiang
• Peng Jin
• Wenfeng Wei
• Wei Jiang

抄録

外傷性脳損傷（TBI）は、その高い死亡率と罹患率の高さから、重要な研究課題となっています。本研究では、アポトーシスとグラスゴーアウトカムスケール（GOS）との関連を解析し、TBI転帰のバイオマーカーとしてのアポトーシスの可能性を検討した。2018年1月から2019年12月までの間に、江蘇大学付属武進病院脳神経外科にて重症TBI患者を募集した。対照群として健常者を募集した。脳脊髄液（CSF）中のカスパーゼ-3、チトクロームc、sFas、カスパーゼ-9の濃度を酵素結合免疫吸着アッセイ（ELISA）で分析した。GOSと臨床変数である年齢，性別，Glasgow Coma Scale（GCS）スコア，頭蓋内圧（ICP），脳灌流圧（CPP），コンピュータ断層撮影（CT）所見，およびアポトーシス因子との関連をロジスティック回帰法を用いて検討した．TBI群のカスパーゼ-3、チトクロームc、sFas、カスパーゼ-9は対照群に比べて有意に高値を示した（P"Zs_200A"<"Zs_200A".05）。ロジスティック回帰の結果、ICPとカスパーゼ-3はTBI後6カ月時点の転帰の有意な予測因子であった（P"Zs_200A"<"Zs_200A".05）。AUCはICPが0.925、カスパーゼ-3が0.888であった。我々は，重症TBI後の患者のCSFにおいて，カスパーゼ-3，シトクロムC，sFas，カスパーゼ-9が有意に増加していることを示し，さらに，ICPとカスパーゼ-3が有意に増加していることを明らかにした．さらに、ICPとcaspase-3は別々の因子ではなく、併用した方が転帰予測の信頼性が高いことを明らかにした。

Traumatic brain injury (TBI), due to its high mortality and morbidity, is an important research topic. Apoptosis plays a pathogenic role in a series of neurological disorders, from neurodegenerative diseases to acute neurological lesions.In this study, we analyzed the association between apoptosis and the Glasgow Outcome Scale (GOS), to examine the potential of apoptosis as a biomarker for a TBI outcome. Patients with severe TBI were recruited at the Department of Neurosurgery, Wujin Hospital Affiliated with Jiangsu University, between January 2018 and December 2019. As a control group, healthy subjects were recruited. The concentrations of caspase-3, cytochrome c, sFas, and caspase-9 in the cerebrospinal fluid (CSF) were analyzed by enzyme-linked immunosorbent assay (ELISA). The association between the GOS and the clinical variables age, sex, initial Glasgow Coma Scale (GCS) score, intracranial pressure (ICP), cerebral perfusion pressure (CPP), initial computed tomography (CT) findings, and apoptotic factors was determined using logistic regression. The area under the receiver operator characteristic (ROC) curve (AUC), and thus the sensitivity and specificity of each risk factor, were obtained.The levels of caspase-3, cytochrome c, sFas, and caspase-9 in the TBI group were significantly higher than those in the control group (P < .05). The logistic regression results showed that ICP and caspase-3 were significant predictors of outcome at 6 months post-TBI (P < .05). The AUC was 0.925 and 0.888 for ICP and caspase-3, respectively. However, the AUC for their combined prediction was 0.978, with a specificity and sensitivity of 96.0% and 95.2%, respectively, showing that the combined prediction was more reliable than that of the 2 separate factors.We demonstrated that caspase-3, cytochrome C, sFas, and caspase-9 were significantly increased in the CSF of patients following severe TBI. Furthermore, we found that ICP and caspase-3 were more reliable for outcome prediction in combination, rather than separately.