WONOEP评价：癫痫的分子和细胞生物标记物_Journal of Epilepsy

Authors：

WalkerLauren E , JanigroDamir , HeinemannUwe , 江欣玥 , 慕洁

Corresponding author：

Keywords：

炎症; 血脑屏障; 高迁移率组框1(HMGB1); S100B; 脑源性神经营养因子; 胰岛素样生长因子

DOI：

10.7507/2096-0247.20170041

Video：

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外周生物标志物具有许多潜在用途，可用于癫痫的治疗、预测、预后和药物安全监视作用。目前为止，虽然多个候选标记物在研究中，但还没有单一的外周生物标记物已经证明有效。文章中讨论的重点领域，包括炎症、血脑屏障功能障碍、氧化还原改变、代谢、激素和生长因子。

Citation： WalkerLauren E, JanigroDamir, HeinemannUwe, 江欣玥, 慕洁. WONOEP评价：癫痫的分子和细胞生物标记物. Journal of Epilepsy, 2017, 3(3): 267-275. doi: 10.7507/2096-0247.20170041 Copy

1.	Hulka B. Overview of biological markers. In Hulka BS, Ja G, Barbara S Hulka, Timothy C Wilcosky, Jack D. Griffith(Ed) Biological markersin epidemiology. New York: Oxford University Press, 1990: 3-15.
2.	Biomarkers Definitions Working G. Biomarkers and surrogate endpoints: preferred definitions and conceptual frame work. Clin Pharmacol Ther, 2001, 69(7): 89-95.
3.	Marchi N, Granata T, Janigro D. Inflammatory pathways of seizure disorders. Trends Neurosci, 2014, 37(9): 55-65.
4.	Janigro D. Are you in or out Leukocyte, ion, and neurotransmitter perme ability across the epileptic blood-brain barrier. Epilepsia, 2012, 53(Suppl 1): 26-34.
5.	Marchi N, Granata T, Freri E, et al. Efficacy of anti-inflammatory therapyin a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS ONE, 2011, 42(6): e18200.
6.	Hulkkonen J, Koskikallio E, Rainesalo S, et al. The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients. Epilepsy Res, 2004, 59(3): 199-205.
7.	Maroso M, Balosso S, Ravizza T, et al. Interleukin-1beta biosynthesis in hibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neuro therapeutics, 2011, 8(1): 304-315.
8.	Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol, 2011, 7(2): 31-40.
9.	Lehtimaki KA, Liimatainen S, Peltola J, et al.The serum level of interleukin-6 in patients with intellectual disability and refractory epilepsy. Epilepsy Res, 2011, 95(8): 184-187.
10.	Mao LY, Ding J, Peng WF, et al. Interictal interleukin-17A levels areelevated and correlate with seizure severity of epilepsy patients. Epilepsia, 2013, 54(2): e142-145.
11.	Diamond ML, Ritter AC, Failla MD, et al. IL-1beta associations with posttraumatic epilepsy development: a genetics and biomarker cohortstudy. Epilepsia, 2014, 55(6): 1109-1119.
12.	Wathen C, Janigro D. IL-1beta associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia, 2014, 55(2): 1313.
13.	Maroso M, Balosso S, Ravizza T, et al. Toll-like receptor 4 and high mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med, 2010, 16(2): 413-419.
14.	Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol, 2011, 29(1): 139-162.
15.	Yang H, Lundback P, Ottosson L, et al. Redox modification of cysteine residues regulates the cytokine activity of high mobility groupbox-1(HMGB1).Mol Med, 2012, 18(3): 250-259.
16.	Zurolo E, Iyer A, Maroso M, et al.Activation of Toll-like receptor, RAGE and HMGB1 signaling in malformations of cortical development. Brain, 2011, 134(7): 1015-1032.
17.	Schiraldi M, Raucci A, Munoz LM, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med, 2012, 209(5): 551-563.
18.	Balosso S, Liu J, Bianchi ME, et al. Disulfide-containing high mobility group box-1 promotes N-Methyl-d-aspartate receptor function and excitotoxicity by activating toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal, 2014, 21(12): 1726-1740.
19.	Pilzweger C, Holdenrieder S. Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases. Diagnostics (Basel), 2015, 5(3): 219-253.
20.	Musumeci D, Roviello GN, Montesarchio D. An overview on HMGB1inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacol The, 2014, 141(3): 347-357.
21.	Fregni R, De Poli A. Convulsive state produced by various types of shock; conduct of three barriers (blood-aqueous, blood-labyrinthinefluids, and blood-liquor [spinal fluid]) with reference to some convulsivestates. AMA Arch Otolaryngol, 1954, 60(10): 149-153.
22.	Klatzo I, Piraux A, Laskowski EJ. The relationship between edema, blood-brain-barrier and tissue elements in a local brain injury. J Neuropathol Exp Neurol, 1958, 17(2): 548-564.
23.	Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia, 2006, 47(10): 1761-1774.
24.	de Vries HE, Kooij G, Frenkel D, et al. Inflammatory events at blood brain barrier in neuro inflammatory and neurodegenerative disorders: implications for clinical disease. Epilepsia, 2012, 53(Suppl 6): 45-52.
25.	Seiffert E, Dreier JP, Ivens S, et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci, 2004, 24(3): 7829-7836.
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27.	Tomkins O, Feintuch A, Benifla M, et al.Blood-brain barrier break down following traumatic brain injury: a possible role in post traumatic epilepsy. Cardiovasc Psychiatry Neurol, 2011, 20(5): 765923.
28.	Raabe A, Schmitz AK, Pernhorst K, et al. Cliniconeuro pathologic correlations show astroglial albumin storage as a common factor in epileptogenic vascular lesions. Epilepsia, 2012, 53(4): 539-548.
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32.	Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption. Epilepsia, 2007, 48(9): 732-742.
33.	Rigau V, Morin M, Rousset MC, et al.Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain, 2007, 130(8): 1942-1956.
34.	Dombrowski SM, Desai SY, Marroni M, et al. Over expression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia, 2001, 42(9): 1501-1506.
35.	Ghosh C, Puvenna V, Gonzalez-Martinez J, et al. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: a synergistic role in neurological diseases. Curr Drug Metab, 2011, 12(4): 742-749.
36.	Cornford EM, Hyman S, Cornford ME, et al. Interictal seizure resections show two configurations of endothelial Glut1 glucose transporter in the human blood-brain barrier. J Cereb Blood Flow Metab, 1998, 18(5): 26-42.
37.	Kapural M, Krizanac-Bengez L, Barnett G, et al. Serum S-100 beta as a possible marker of blood-brain barrier disruption. Brain Res, 2002, 940(3): 102-104.
38.	Marchi N, Cavaglia M, Fazio V, et al.Peripheral markers of blood brain barrier damage. Clin Chim Acta, 2004, 342(11): 1-12.
39.	Hoffmann A, Bredno J, Wendland MF, et al. Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology. Stroke, 2011, 42(5): 2054-2060.
40.	Blyth BJ, Farhavar A, Gee C, et al. Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma, 2009, 26(8): 1497-1507.
41.	Unden L, Calcagnile O, Unden J, et al. Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults. BMC Med, 2015, 13(2): 292.
42.	Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma, 2010, 27(3): 1529-1540.
43.	Biberthaler P, Mussack T, Kanz KG, et al. Identification of high-risk patients after minor craniocerebral trauma. Measurement of nerve tissue protein S 100. Unfallchirurg, 2004, 107(12): 197-202.
44.	Li J, Yu C, Sun Y, et al. Serum ubiquity in c-terminal hydrolase L1 as abiomarker for traumatic brain injury: a systematic review and metaanalysis. Am J Emerg Med, 2015, 33(2): 1191-1196.
45.	Heidari K, Vafaee A, Rastekenari AM, et al. S100B protein as ascreening tool for computed tomography findings after mild traumaticbrain injury systematic review and meta-analysis. Brain Inj, 2015, 11(7): 1-12.
46.	Bernardi S, Trimble MR, Frackowiak RS, et al. An interictal study ofpartial epilepsy using positron emission tomography and the oxygen-15 inhalation technique. J Neurol Neurosurg Psychiatry, 1983, 46(7): 473-477.
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48.	Schuchmann S, Kovacs R, Kann O, et al. Monitoring NAD(P)H autofluorescence to assess mitochondrial metabolic functions in rat hippocampal-entorhinal cortex slices. Brain Res Brain Res Protoc, 2001, 7(2): 267-276.
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52.	Patel M, Li QY, Chang LY, et al. Activation of NADPH oxidase and extra cellular superoxide production in seizure-induced hippo campal damage. J Neurochem, 2005, 92(3): 123-131.
53.	Kovac S, Domijan AM, Walker MC, et al. Seizure activity results in calcium-and mitochondria-independent ROS production via NADPH and xanthine oxidase activation. Cell Death Dis, 2014, 5(2): e1442.
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56.	Patel M, Liang LP, Roberts LJ. Enhanced hippocampal F2-isoprostaneformation following kainate-induced seizures. J Neurochem, 2001, 79(3): 1065-1070.
57.	Grosso S, Longini M, Rodriguez A, et al. Oxidative stress in children affected by epileptic encephalopathies. J Neurol Sci, 2011, 300(8): 103-106.
58.	Tanuma N, Miyata R, Nakajima K, et al. Changes in cerebro spinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures. Mediators Inflamm, 2014, 101(4): 564091.
59.	Mueller SG, Trabesinger AH, Boesiger P, et al. Brain glutathione levels in patients with epilepsy measured by in vivo H-MRS. Neurology, 2001, 57(4): 1422-1427.
60.	Liang LP, Patel M. Seizure-induced changes in mitochondrial redox status. Free Radic Biol Med, 2006, 40(2): 316-322.
61.	Heischmann SQK, Cruickshank-Quinn C, Liang LP, et al. Metabolic changes in rat plasma and hippocampus in the kainic acid model of acquired epilepsy determined by LC-MS metabolomics analysis. American Epilepsy Society Abstracts, 2014.
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1. Hulka B. Overview of biological markers. In Hulka BS, Ja G, Barbara S Hulka, Timothy C Wilcosky, Jack D. Griffith(Ed) Biological markersin epidemiology. New York: Oxford University Press, 1990: 3-15.
2. Biomarkers Definitions Working G. Biomarkers and surrogate endpoints: preferred definitions and conceptual frame work. Clin Pharmacol Ther, 2001, 69(7): 89-95.
3. Marchi N, Granata T, Janigro D. Inflammatory pathways of seizure disorders. Trends Neurosci, 2014, 37(9): 55-65.
4. Janigro D. Are you in or out Leukocyte, ion, and neurotransmitter perme ability across the epileptic blood-brain barrier. Epilepsia, 2012, 53(Suppl 1): 26-34.
5. Marchi N, Granata T, Freri E, et al. Efficacy of anti-inflammatory therapyin a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS ONE, 2011, 42(6): e18200.
6. Hulkkonen J, Koskikallio E, Rainesalo S, et al. The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients. Epilepsy Res, 2004, 59(3): 199-205.
7. Maroso M, Balosso S, Ravizza T, et al. Interleukin-1beta biosynthesis in hibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neuro therapeutics, 2011, 8(1): 304-315.
8. Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol, 2011, 7(2): 31-40.
9. Lehtimaki KA, Liimatainen S, Peltola J, et al.The serum level of interleukin-6 in patients with intellectual disability and refractory epilepsy. Epilepsy Res, 2011, 95(8): 184-187.
10. Mao LY, Ding J, Peng WF, et al. Interictal interleukin-17A levels areelevated and correlate with seizure severity of epilepsy patients. Epilepsia, 2013, 54(2): e142-145.
11. Diamond ML, Ritter AC, Failla MD, et al. IL-1beta associations with posttraumatic epilepsy development: a genetics and biomarker cohortstudy. Epilepsia, 2014, 55(6): 1109-1119.
12. Wathen C, Janigro D. IL-1beta associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia, 2014, 55(2): 1313.
13. Maroso M, Balosso S, Ravizza T, et al. Toll-like receptor 4 and high mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med, 2010, 16(2): 413-419.
14. Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol, 2011, 29(1): 139-162.
15. Yang H, Lundback P, Ottosson L, et al. Redox modification of cysteine residues regulates the cytokine activity of high mobility groupbox-1(HMGB1).Mol Med, 2012, 18(3): 250-259.
16. Zurolo E, Iyer A, Maroso M, et al.Activation of Toll-like receptor, RAGE and HMGB1 signaling in malformations of cortical development. Brain, 2011, 134(7): 1015-1032.
17. Schiraldi M, Raucci A, Munoz LM, et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med, 2012, 209(5): 551-563.
18. Balosso S, Liu J, Bianchi ME, et al. Disulfide-containing high mobility group box-1 promotes N-Methyl-d-aspartate receptor function and excitotoxicity by activating toll-like receptor 4-dependent signaling in hippocampal neurons. Antioxid Redox Signal, 2014, 21(12): 1726-1740.
19. Pilzweger C, Holdenrieder S. Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases. Diagnostics (Basel), 2015, 5(3): 219-253.
20. Musumeci D, Roviello GN, Montesarchio D. An overview on HMGB1inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacol The, 2014, 141(3): 347-357.
21. Fregni R, De Poli A. Convulsive state produced by various types of shock; conduct of three barriers (blood-aqueous, blood-labyrinthinefluids, and blood-liquor [spinal fluid]) with reference to some convulsivestates. AMA Arch Otolaryngol, 1954, 60(10): 149-153.
22. Klatzo I, Piraux A, Laskowski EJ. The relationship between edema, blood-brain-barrier and tissue elements in a local brain injury. J Neuropathol Exp Neurol, 1958, 17(2): 548-564.
23. Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia, 2006, 47(10): 1761-1774.
24. de Vries HE, Kooij G, Frenkel D, et al. Inflammatory events at blood brain barrier in neuro inflammatory and neurodegenerative disorders: implications for clinical disease. Epilepsia, 2012, 53(Suppl 6): 45-52.
25. Seiffert E, Dreier JP, Ivens S, et al. Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci, 2004, 24(3): 7829-7836.
26. Gorter JA, van Vliet EA, Aronica E. Status epilepticus, blood-brain barrier disruption, inflammation, and epileptogenesis. Epilepsy Behav, 2015, 49(5): 13-16.
27. Tomkins O, Feintuch A, Benifla M, et al.Blood-brain barrier break down following traumatic brain injury: a possible role in post traumatic epilepsy. Cardiovasc Psychiatry Neurol, 2011, 20(5): 765923.
28. Raabe A, Schmitz AK, Pernhorst K, et al. Cliniconeuro pathologic correlations show astroglial albumin storage as a common factor in epileptogenic vascular lesions. Epilepsia, 2012, 53(4): 539-548.
29. Marchi N, Granata T, Ghosh C, et al. Blood-brain barrier dysfunction and epilepsy: pathophysiologic role and therapeutic approaches. Epilepsia, 2012, 53(11): 1877-1886.
30. Penfield W. Carpenter lecture: the influence of the diencephalon and hypophysis upon general autonomic function. Bull NY Acad Med, 1933, 9(2): 613-637.
31. Janigro D, Leaman SM, Stanness KA. Dynamic modeling of the blood brain barrier: a novel tool for studies of drug delivery to the brain. Pharm Sci Technolo Today, 1999, 2(1): 7-12.
32. Marchi N, Angelov L, Masaryk T, et al. Seizure-promoting effect of blood-brain barrier disruption. Epilepsia, 2007, 48(9): 732-742.
33. Rigau V, Morin M, Rousset MC, et al.Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain, 2007, 130(8): 1942-1956.
34. Dombrowski SM, Desai SY, Marroni M, et al. Over expression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia, 2001, 42(9): 1501-1506.
35. Ghosh C, Puvenna V, Gonzalez-Martinez J, et al. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: a synergistic role in neurological diseases. Curr Drug Metab, 2011, 12(4): 742-749.
36. Cornford EM, Hyman S, Cornford ME, et al. Interictal seizure resections show two configurations of endothelial Glut1 glucose transporter in the human blood-brain barrier. J Cereb Blood Flow Metab, 1998, 18(5): 26-42.
37. Kapural M, Krizanac-Bengez L, Barnett G, et al. Serum S-100 beta as a possible marker of blood-brain barrier disruption. Brain Res, 2002, 940(3): 102-104.
38. Marchi N, Cavaglia M, Fazio V, et al.Peripheral markers of blood brain barrier damage. Clin Chim Acta, 2004, 342(11): 1-12.
39. Hoffmann A, Bredno J, Wendland MF, et al. Validation of in vivo magnetic resonance imaging blood-brain barrier permeability measurements by comparison with gold standard histology. Stroke, 2011, 42(5): 2054-2060.
40. Blyth BJ, Farhavar A, Gee C, et al. Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma, 2009, 26(8): 1497-1507.
41. Unden L, Calcagnile O, Unden J, et al. Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults. BMC Med, 2015, 13(2): 292.
42. Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma, 2010, 27(3): 1529-1540.
43. Biberthaler P, Mussack T, Kanz KG, et al. Identification of high-risk patients after minor craniocerebral trauma. Measurement of nerve tissue protein S 100. Unfallchirurg, 2004, 107(12): 197-202.
44. Li J, Yu C, Sun Y, et al. Serum ubiquity in c-terminal hydrolase L1 as abiomarker for traumatic brain injury: a systematic review and metaanalysis. Am J Emerg Med, 2015, 33(2): 1191-1196.
45. Heidari K, Vafaee A, Rastekenari AM, et al. S100B protein as ascreening tool for computed tomography findings after mild traumaticbrain injury systematic review and meta-analysis. Brain Inj, 2015, 11(7): 1-12.
46. Bernardi S, Trimble MR, Frackowiak RS, et al. An interictal study ofpartial epilepsy using positron emission tomography and the oxygen-15 inhalation technique. J Neurol Neurosurg Psychiatry, 1983, 46(7): 473-477.
47. Henry TR, Engel J Jr, Mazziotta JC. Clinical evaluation of interictal fluorine-18-fluorodeoxyglucose PET in partial epilepsy. J Nucl Med, 1993, 34(8): 1892-1898.
48. Schuchmann S, Kovacs R, Kann O, et al. Monitoring NAD(P)H autofluorescence to assess mitochondrial metabolic functions in rat hippocampal-entorhinal cortex slices. Brain Res Brain Res Protoc, 2001, 7(2): 267-276.
49. Denton RM, Mc Cormack JG. The calcium sensitive dehydrogenases of vertebrate mitochondria. Cell Calcium, 1986, 7(2): 377-386.
50. Flynn JM, Czerwieniec GA, Choi SW, et al. Proteogenomics of synaptosomal mitochondrial oxidative stress. Free Radic Biol Med, 2012, 53(8): 1048-1060.
51. Malkov A, Ivanov AI, Popova I, et al. Reactive oxygen species initiatea metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression. J Cereb Blood Flow Metab, 2014, 34(6): 1540-1549.
52. Patel M, Li QY, Chang LY, et al. Activation of NADPH oxidase and extra cellular superoxide production in seizure-induced hippo campal damage. J Neurochem, 2005, 92(3): 123-131.
53. Kovac S, Domijan AM, Walker MC, et al. Seizure activity results in calcium-and mitochondria-independent ROS production via NADPH and xanthine oxidase activation. Cell Death Dis, 2014, 5(2): e1442.
54. Dalle-Donne I, Rossi R, Colombo R, et al. Biomarkers of oxidative damage in human disease. Clin Chem, 2006, 52(1): 601-623.
55. Liang LP, Ho YS, Patel M. Mitochondrial superoxide production in kainate-induced hippocampal damage. Neuroscience, 2000, 101(2): 563-570.
56. Patel M, Liang LP, Roberts LJ. Enhanced hippocampal F2-isoprostaneformation following kainate-induced seizures. J Neurochem, 2001, 79(3): 1065-1070.
57. Grosso S, Longini M, Rodriguez A, et al. Oxidative stress in children affected by epileptic encephalopathies. J Neurol Sci, 2011, 300(8): 103-106.
58. Tanuma N, Miyata R, Nakajima K, et al. Changes in cerebro spinal fluid biomarkers in human herpesvirus-6-associated acute encephalopathy/febrile seizures. Mediators Inflamm, 2014, 101(4): 564091.
59. Mueller SG, Trabesinger AH, Boesiger P, et al. Brain glutathione levels in patients with epilepsy measured by in vivo H-MRS. Neurology, 2001, 57(4): 1422-1427.
60. Liang LP, Patel M. Seizure-induced changes in mitochondrial redox status. Free Radic Biol Med, 2006, 40(2): 316-322.
61. Heischmann SQK, Cruickshank-Quinn C, Liang LP, et al. Metabolic changes in rat plasma and hippocampus in the kainic acid model of acquired epilepsy determined by LC-MS metabolomics analysis. American Epilepsy Society Abstracts, 2014.
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