脑损伤生物标记物研究进展_Journal of Epilepsy

Authors：

索桂海 ^1,2 ,  汤继宏 ¹

1. ;
2. ;

Corresponding author：

汤继宏, Email: tjhzsh@126.com

Keywords：

脑损伤; 生物标记物; 研究进展

DOI：

10.7507/2096-0247.20190062

Video：

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脑损伤是临床常见病、多发病，可导致脑瘫、癫痫、精神运动发育迟缓等后遗症及各种功能障碍，严重影响患者的生活质量。脑损伤病因复杂，临床表现常缺乏特异性，临床常用的脑电图、影像学检查等方法又存在一定的局限性及滞后性，因此临床医生在判断脑损伤部位、严重程度时面临较大困难。体液生物标记物水平在脑损伤后早期即发生变化，这些生物标记物能预测早期脑损伤、鉴定脑损伤区域、评估预后，临床意义重大，受到广大科研工作者及临床医师的重视。文章对目前正在研究的相对具有较好应用前景的脑损伤生物标志物进行相关综述。

Citation： 索桂海, 汤继宏. 脑损伤生物标记物研究进展. Journal of Epilepsy, 2019, 5(5): 382-385. doi: 10.7507/2096-0247.20190062 Copy

1.	Mouhieddine TH, Houjeiri LE, Sabra M, et al. CNS Trauma Biomarkers and Surrogate Endpoints Pipeline from Bench to Bedside[M] // Brain Neurotrauma Molecular, Neuropsychological, and Rehabilitation Aspects. Edition 1. Florida: CRC Press, 2015: 275-288.
2.	Louis ED, Ma K, Babij R, et al. Neurofilament protein levels: quantitative analysis in essential tremor cerebellar cortex. Neurosci Lett, 2012, 518(1): 49-54.
3.	Dyakin VV, Chen Y, Branch CA, et al. The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models. NeuroImage, 2010, 51(3): 1098-1105.
4.	Michael K, Teunissen CE, Markus O, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol, 2018, 14(10): 577-589.
5.	Gattringer T, Pinter D, Enzinger C, et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology, 2017, 89(20): 2108-2114.
6.	Tiedt S, Duering M, Barro C, et al. Serum neurofilament light a biomarker of neuroaxonal injury after ischemic stroke. Neurology, 2018, 91(14): 1338-1347.
7.	Pujol-Calderon F, Portelius E, Zetterberg H, et al. Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke. Neurosci lett, 2019, 698: 58-63.
8.	Evers KS, Atkinson A, Barro C, et al. Neurofilament as neuronal injury blood marker in preeclampsia. Hypertension, 2018, 71(6): 1178-1184.
9.	De Schaepdryver M, Jeromin A, Gille B, et al. Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. JNeurol Neurosurg Psychiatry, 2018, 89(4): 367-373.
10.	AndersonKJ, Scheff SW, Miller KM, et al. The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. J Neurotrauma, 2008, 25(9): 1079-1085.
11.	Singh A, Kumar B, Ali S, et al. Phosphorylated neurofilament heavy: a potential blood biomarker to evaluate the severity of acute spinal cord injuries in adults. Int J Crit Illn Inj Sci, 2017, 7(4): 212-217.
12.	Yang Z, Zhu T, Mondello S, et al. Serum-based phosphoneurofilament-heavy protein as theranostic biomarker in three models of traumatic brain injury: an operation brain trauma therapy study, J. Neurotrauma, 2019, 36(2): 348-359.
13.	Martinez-Morillo E, Childs C, Garcia BP, et al. Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury. Clin Chem Lab Med, 2015, 53(10): 1575-1584.
14.	Guingab-Cagmat JD, Cagmat EB, Hayes RL, et al. Integration of proteomics, bioinformatics, and systems biology in traumatic brain injury biomarker discovery. Front Neurol, 2013, 4: 61.
15.	Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders. Drug News Perspect, 2007, 20(6): 365-370.
16.	Mondello S, Kobeissy F, Vestri A, et al. Serum concentrations of ubiquitin C-terminal hydrolase-L1 and glial gibrillary acidic protein after pediatric traumatic brain injury. Sci Rep, 2016, 6: 28203.
17.	蒋曙红, 王金秀, 张一鸣, 等. 亚低温治疗对缺血性脑病新生儿血清神经质酸性蛋白和泛素羟基末端水解酶L1的影响. 中国当代儿科杂志, 2014, 16(12): 1193-1196.
18.	Massaro AN, Wu YW, Bammler TK, et al. Plasma biomarkers of brain injury in neonatal hypoxic-ischemic encephalopathy. J Pediatr, 2018, 194: 67-75.
19.	Guingab-Cagmat JD, Cagmat EB, Hayes RL, et al. Integration of proteomics, bioinformatics, and systems biology in traumatic brain injury biomarker discovery. FrontNeurol, 2013, 4: 61.
20.	Papa L, Rosenthal K, Silvestri F, et al. Evaluation of alpha-II-spectrin breakdown products as potential biomarkers for early recognition and severity of aneurysmal subarachnoid hemorrhage. Sci Rep, 2018, 8(1): 13308.
21.	Cardali S, Maugeri R. Detection of alpha II-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci, 2006, 50(2): 25-31.
22.	Mondello S, Robicsek SA, GabrielliA, et al. AlphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma, 2010, 27(7): 1203-1213.
23.	Imam SS, Gad GI, Aterf SH, et al. Gord blood brain derived neurotrophic factor: diagnostic and prognostic marker in full-term newborns with perinatal asphyxia. Biol Sci, 2009, 12: 1498-1504.
24.	Korley FK, Diaz-Arrastia R, Wu AHB, et al. Circulating brain derived neurotrophic factor has diagnostic and prognostic value in traumatic brain injury. JNeurotrauma, 2016, 33(2): 215-225.
25.	Ismail AM, Babers GM, Rehany MAE. Brain-derived neurotrophic factor in sera of breastfed epileptic infants and in breastmilk of their mothers. Breastfeed Med, 2015, 10(5): 277-282.
26.	Chen NC, Chuang YC, Huang CW, et al. Interictal serum brain-derived neurotrophic factor level reflects white matter integrity, epilepsy severity, and cognitive dysfunction in chronic temporal lobe epilepsy. Epilepsy Behav, 2016, 59: 147-154.
27.	Florio P, Perrone S, Luisi S, et al. Increased plasma concentrations of activin a redict intraventricular hemorrhage in preterm newborns. Clin Chem, 2006, 52(8): 1516-1521.
28.	Dong XQ, Yu WH, Zhu Q, et al. Changes in plasma thrombospondin-1 concentrations following acute intracerebral hemorrhage. Clin Chim Acta, 2015, 450: 349-355.
29.	赵新玲, 陶然, 杨园, 等. 血小板反应蛋白1(THBS-1)与急性缺血性脑卒中诊断和预后的相关性研究. 华中科技大学学报(医学版), 2018, 49(5): 564-567.
30.	Ji Q, Ji Y, Peng J, et al. Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One, 2016, 11(9): e0163645.
31.	Zhou J, Chen L, Chen B, et al. Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol, 2018, 18(1): 198.
32.	Werner JK, Stevens RD. Traumatic brain injury: recent advances in plasticity and regeneration. Curr Opin Neurol, 2015, 28(6): 565-573.
33.	Lv H, Wang Q, Wu S, et al. Neonatal hypoxic Ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid. Clin Chim Acta, 2015, 450: 282-297.
34.	Hua YJ, Tang ZY, Tu K, et al. Identification and target prediction of miRNAs specifically expressed on rat neural tissue. BMC Genomics, 2012, 10: 214-220.
35.	Chen F, Du Y, Esposito E, et al. Effects of focal cerebral ischemia on exosomal versus serum miR126. Transl Stroke Res, 2015, 6(6): 1-7.
36.	金雅, 肖珮, 赵青, 等. miRNA-210在新生儿窒息早期外周血中差异表达的分析. 广东医科大学学报, 2018, 36(5): 564-567.
37.	Weiss JB, Eisenhardt SU, Stark GB, et al. MicroRNAs in ischemia-reperfusion injury. Am J Cardiovasc Dis, 2012, 2: 237-247.
38.	Di Pietro V, Ragusa M, Davies D, et al. MicroRNAs as novel biomarkers for the diagnosis and prognosis of mild and severe traumatic brain injury. JNeurotrauma, 2017, 34(11): 1948-1956.
39.	Zhou J, Zhang J. Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. MolMedRep, 2014, 10(2): 971-976.

1. Mouhieddine TH, Houjeiri LE, Sabra M, et al. CNS Trauma Biomarkers and Surrogate Endpoints Pipeline from Bench to Bedside[M] // Brain Neurotrauma Molecular, Neuropsychological, and Rehabilitation Aspects. Edition 1. Florida: CRC Press, 2015: 275-288.
2. Louis ED, Ma K, Babij R, et al. Neurofilament protein levels: quantitative analysis in essential tremor cerebellar cortex. Neurosci Lett, 2012, 518(1): 49-54.
3. Dyakin VV, Chen Y, Branch CA, et al. The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models. NeuroImage, 2010, 51(3): 1098-1105.
4. Michael K, Teunissen CE, Markus O, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol, 2018, 14(10): 577-589.
5. Gattringer T, Pinter D, Enzinger C, et al. Serum neurofilament light is sensitive to active cerebral small vessel disease. Neurology, 2017, 89(20): 2108-2114.
6. Tiedt S, Duering M, Barro C, et al. Serum neurofilament light a biomarker of neuroaxonal injury after ischemic stroke. Neurology, 2018, 91(14): 1338-1347.
7. Pujol-Calderon F, Portelius E, Zetterberg H, et al. Neurofilament changes in serum and cerebrospinal fluid after acute ischemic stroke. Neurosci lett, 2019, 698: 58-63.
8. Evers KS, Atkinson A, Barro C, et al. Neurofilament as neuronal injury blood marker in preeclampsia. Hypertension, 2018, 71(6): 1178-1184.
9. De Schaepdryver M, Jeromin A, Gille B, et al. Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. JNeurol Neurosurg Psychiatry, 2018, 89(4): 367-373.
10. AndersonKJ, Scheff SW, Miller KM, et al. The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. J Neurotrauma, 2008, 25(9): 1079-1085.
11. Singh A, Kumar B, Ali S, et al. Phosphorylated neurofilament heavy: a potential blood biomarker to evaluate the severity of acute spinal cord injuries in adults. Int J Crit Illn Inj Sci, 2017, 7(4): 212-217.
12. Yang Z, Zhu T, Mondello S, et al. Serum-based phosphoneurofilament-heavy protein as theranostic biomarker in three models of traumatic brain injury: an operation brain trauma therapy study, J. Neurotrauma, 2019, 36(2): 348-359.
13. Martinez-Morillo E, Childs C, Garcia BP, et al. Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury. Clin Chem Lab Med, 2015, 53(10): 1575-1584.
14. Guingab-Cagmat JD, Cagmat EB, Hayes RL, et al. Integration of proteomics, bioinformatics, and systems biology in traumatic brain injury biomarker discovery. Front Neurol, 2013, 4: 61.
15. Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders. Drug News Perspect, 2007, 20(6): 365-370.
16. Mondello S, Kobeissy F, Vestri A, et al. Serum concentrations of ubiquitin C-terminal hydrolase-L1 and glial gibrillary acidic protein after pediatric traumatic brain injury. Sci Rep, 2016, 6: 28203.
17. 蒋曙红, 王金秀, 张一鸣, 等. 亚低温治疗对缺血性脑病新生儿血清神经质酸性蛋白和泛素羟基末端水解酶L1的影响. 中国当代儿科杂志, 2014, 16(12): 1193-1196.
18. Massaro AN, Wu YW, Bammler TK, et al. Plasma biomarkers of brain injury in neonatal hypoxic-ischemic encephalopathy. J Pediatr, 2018, 194: 67-75.
19. Guingab-Cagmat JD, Cagmat EB, Hayes RL, et al. Integration of proteomics, bioinformatics, and systems biology in traumatic brain injury biomarker discovery. FrontNeurol, 2013, 4: 61.
20. Papa L, Rosenthal K, Silvestri F, et al. Evaluation of alpha-II-spectrin breakdown products as potential biomarkers for early recognition and severity of aneurysmal subarachnoid hemorrhage. Sci Rep, 2018, 8(1): 13308.
21. Cardali S, Maugeri R. Detection of alpha II-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci, 2006, 50(2): 25-31.
22. Mondello S, Robicsek SA, GabrielliA, et al. AlphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma, 2010, 27(7): 1203-1213.
23. Imam SS, Gad GI, Aterf SH, et al. Gord blood brain derived neurotrophic factor: diagnostic and prognostic marker in full-term newborns with perinatal asphyxia. Biol Sci, 2009, 12: 1498-1504.
24. Korley FK, Diaz-Arrastia R, Wu AHB, et al. Circulating brain derived neurotrophic factor has diagnostic and prognostic value in traumatic brain injury. JNeurotrauma, 2016, 33(2): 215-225.
25. Ismail AM, Babers GM, Rehany MAE. Brain-derived neurotrophic factor in sera of breastfed epileptic infants and in breastmilk of their mothers. Breastfeed Med, 2015, 10(5): 277-282.
26. Chen NC, Chuang YC, Huang CW, et al. Interictal serum brain-derived neurotrophic factor level reflects white matter integrity, epilepsy severity, and cognitive dysfunction in chronic temporal lobe epilepsy. Epilepsy Behav, 2016, 59: 147-154.
27. Florio P, Perrone S, Luisi S, et al. Increased plasma concentrations of activin a redict intraventricular hemorrhage in preterm newborns. Clin Chem, 2006, 52(8): 1516-1521.
28. Dong XQ, Yu WH, Zhu Q, et al. Changes in plasma thrombospondin-1 concentrations following acute intracerebral hemorrhage. Clin Chim Acta, 2015, 450: 349-355.
29. 赵新玲, 陶然, 杨园, 等. 血小板反应蛋白1(THBS-1)与急性缺血性脑卒中诊断和预后的相关性研究. 华中科技大学学报(医学版), 2018, 49(5): 564-567.
30. Ji Q, Ji Y, Peng J, et al. Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One, 2016, 11(9): e0163645.
31. Zhou J, Chen L, Chen B, et al. Increased serum exosomal miR-134 expression in the acute ischemic stroke patients. BMC Neurol, 2018, 18(1): 198.
32. Werner JK, Stevens RD. Traumatic brain injury: recent advances in plasticity and regeneration. Curr Opin Neurol, 2015, 28(6): 565-573.
33. Lv H, Wang Q, Wu S, et al. Neonatal hypoxic Ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid. Clin Chim Acta, 2015, 450: 282-297.
34. Hua YJ, Tang ZY, Tu K, et al. Identification and target prediction of miRNAs specifically expressed on rat neural tissue. BMC Genomics, 2012, 10: 214-220.
35. Chen F, Du Y, Esposito E, et al. Effects of focal cerebral ischemia on exosomal versus serum miR126. Transl Stroke Res, 2015, 6(6): 1-7.
36. 金雅, 肖珮, 赵青, 等. miRNA-210在新生儿窒息早期外周血中差异表达的分析. 广东医科大学学报, 2018, 36(5): 564-567.
37. Weiss JB, Eisenhardt SU, Stark GB, et al. MicroRNAs in ischemia-reperfusion injury. Am J Cardiovasc Dis, 2012, 2: 237-247.
38. Di Pietro V, Ragusa M, Davies D, et al. MicroRNAs as novel biomarkers for the diagnosis and prognosis of mild and severe traumatic brain injury. JNeurotrauma, 2017, 34(11): 1948-1956.
39. Zhou J, Zhang J. Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. MolMedRep, 2014, 10(2): 971-976.

Journal of Epilepsy

脑损伤生物标记物研究进展

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