Pre-clinical to Clinical Translational Failures and Current Status of Clinical Trials in Stroke Therapy: A Brief Review.
STAIR criteria
Stroke
cerebral ischemia
clinical trials
neuroprotection
pathophysiology
pharmacotherapy
pre-clinical studies
Journal
Current neuropharmacology
ISSN: 1875-6190
Titre abrégé: Curr Neuropharmacol
Pays: United Arab Emirates
ID NLM: 101157239
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
09
2019
revised:
31
10
2019
accepted:
28
12
2019
pubmed:
15
1
2020
medline:
2
6
2021
entrez:
15
1
2020
Statut:
ppublish
Résumé
In stroke (cerebral ischemia), despite continuous efforts both at the experimental and clinical level, the only approved pharmacological treatment has been restricted to tissue plasminogen activator (tPA). Stroke is the leading cause of functional disability and mortality throughout worldwide. Its pathophysiology starts with energy pump failure, followed by complex signaling cascade that ultimately ends in neuronal cell death. Ischemic cascade involves excessive glutamate release followed by raised intracellular sodium and calcium influx along with free radicals' generation, activation of inflammatory cytokines, NO synthases, lipases, endonucleases and other apoptotic pathways leading to cell edema and death. At the pre-clinical stage, several agents have been tried and proven as an effective neuroprotectant in animal models of ischemia. However, these agents failed to show convincing results in terms of efficacy and safety when the trials were conducted in humans following stroke. This article highlights the various agents which have been tried in the past but failed to translate into stroke therapy along with key points that are responsible for the lagging of experimental success to translational failure in stroke treatment.
Identifiants
pubmed: 31934841
pii: CN-EPUB-103645
doi: 10.2174/1570159X18666200114160844
pmc: PMC7457423
doi:
Substances chimiques
Neuroprotective Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
596-612Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
J Pharmacol Exp Ther. 1998 Nov;287(2):559-66
pubmed: 9808681
J Neurol Sci. 2006 Nov 15;249(2):101-9
pubmed: 17005205
Dev Neurorehabil. 2015;18(5):330-5
pubmed: 24088023
Stroke. 1981 Nov-Dec;12(6):723-5
pubmed: 6272455
Curr Cardiol Rep. 2012 Dec;14(6):761-6
pubmed: 22922833
Rom J Intern Med. 2008;46(1):3-8
pubmed: 19157265
JAMA. 2001 Dec 5;286(21):2673-82
pubmed: 11730442
Stroke. 2009 Feb;40(2):626-31
pubmed: 19095969
Eur J Pharmacol. 1997 Oct 1;336(1):7-14
pubmed: 9384248
Eur J Neurol. 2009 May;16(5):569-75
pubmed: 19236467
Stroke. 2009 Dec;40(12):e647-56
pubmed: 19834012
Neuropharmacology. 1996 Jun;35(6):689-93
pubmed: 8887977
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):2007-12
pubmed: 9050895
Cochrane Database Syst Rev. 2016 Oct 04;10:CD009622
pubmed: 27701753
Stroke. 1990 May;21(5):721-5
pubmed: 2339451
Cerebrovasc Dis. 2009;27(5):485-92
pubmed: 19321945
Cerebrovasc Dis. 2011;32(1):65-71
pubmed: 21613787
Stroke. 1998 May;29(5):1020-30
pubmed: 9596253
Curr Drug Targets CNS Neurol Disord. 2005 Apr;4(2):119-20
pubmed: 15857296
Brain Res. 1996 Nov 25;741(1-2):153-9
pubmed: 9001717
Eur Neurol. 2008;59(1-2):4-14
pubmed: 17917451
Am J Cardiol. 1985 Jan 25;55(3):144B-148B
pubmed: 2578724
J Stroke. 2017 Sep;19(3):286-294
pubmed: 29037005
Stroke. 2003 Feb;34(2):482-7
pubmed: 12574564
Neurology. 1997 Nov;49(5 Suppl 4):S66-9
pubmed: 9371155
Neurology. 2001 Oct 23;57(8):1428-34
pubmed: 11673584
Sci Rep. 2019 Feb 19;9(1):2287
pubmed: 30783142
Stroke. 1989 May;20(5):604-8
pubmed: 2655184
Stroke. 2003 Nov;34(11):2543-8
pubmed: 14563972
Int J Stroke. 2017 Jun;12(4):377-382
pubmed: 28345429
Stroke. 1998 Jan;29(1):12-7
pubmed: 9445321
Neurochem Int. 2016 Jun;96:24-31
pubmed: 27103167
Brain Res. 2007 Oct 24;1176:143-50
pubmed: 17904110
Nat Med. 2001 Apr;7(4):471-7
pubmed: 11283675
Lancet Neurol. 2017 Mar;16(3):217-226
pubmed: 28229893
Acta Neurochir Suppl. 1999;73:45-50
pubmed: 10494340
J Neurochem. 2009 Aug;110(4):1226-40
pubmed: 19549282
Brain Res. 1993 Dec 31;632(1-2):346-50
pubmed: 7908601
J Pharmacol Exp Ther. 1996 Nov;279(2):748-58
pubmed: 8930180
Stroke. 2001 Nov;32(11):2665-74
pubmed: 11692032
Brain Res. 2001 Jan 5;888(1):150-157
pubmed: 11146061
Ann N Y Acad Sci. 1995 Sep 15;765:317-8
pubmed: 7486628
Stroke. 1997 Dec;28(12):2338-46
pubmed: 9412611
Stroke. 2018 May;49(5):1210-1216
pubmed: 29567761
Ann Neurol. 2019 Jan;85(1):125-136
pubmed: 30450637
CNS Drug Rev. 2003 Fall;9(3):253-62
pubmed: 14530797
J Cereb Blood Flow Metab. 1988 Jun;8(3):436-9
pubmed: 2966804
Cerebrovasc Dis. 2001;11 Suppl 1:60-70
pubmed: 11244202
Stroke. 1988 Aug;19(8):1020-6
pubmed: 3400100
Life Sci. 1985 Oct 21;37(16):1475-82
pubmed: 2995747
Cochrane Database Syst Rev. 2012 May 16;(5):CD001928
pubmed: 22592678
Brain Res. 2001 Feb 16;892(1):70-7
pubmed: 11172750
Cerebrovasc Dis. 2000 May-Jun;10(3):165-9
pubmed: 10773641
Circulation. 2007 May 1;115(17):2323-30
pubmed: 17438148
Biomed Res Int. 2018 Oct 16;2018:3706047
pubmed: 30410928
Stroke. 2001 Feb;32(2):553-60
pubmed: 11157196
Brain Res. 2001 Aug 3;909(1-2):46-50
pubmed: 11478919
Stroke. 2002 Jan;33(1):147-52
pubmed: 11779904
J Cell Mol Med. 2011 Aug;15(8):1645-87
pubmed: 20015202
Brain Res. 2007 Nov 21;1181:83-92
pubmed: 17920569
Exp Transl Stroke Med. 2013 Apr 25;5(1):6
pubmed: 23618347
Stroke. 2008 Jun;39(6):1774-8
pubmed: 18403736
Stroke. 2001 Oct;32(10):2433-8
pubmed: 11588338
N Engl J Med. 2007 Aug 9;357(6):562-71
pubmed: 17687131
Stroke. 2016 Nov;47(11):2874-2876
pubmed: 27758945
Acta Neurol Scand. 1996 Jan;93(1):56-60
pubmed: 8825274
NeuroRx. 2004 Jan;1(1):36-45
pubmed: 15717006
Stroke. 1995 Aug;26(8):1438-42; discussion 1443
pubmed: 7631350
Stroke. 2005 Apr;36(4):880-90
pubmed: 15731473
CNS Drugs. 2014 Oct;28(10):929-38
pubmed: 25160686
Life Sci. 1994;55(25-26):2125-34
pubmed: 7997071
Stroke. 1989 Oct;20(10):1383-90
pubmed: 2799870
J Cereb Blood Flow Metab. 1993 Nov;13(6):925-32
pubmed: 8408318
Eur Neurol. 1998 Aug;40(2):78-83
pubmed: 9693236
J Pharmacol Exp Ther. 2001 Feb;296(2):312-21
pubmed: 11160612
J Neurochem. 2001 Apr;77(2):353-71
pubmed: 11299298
Thromb Res. 1999 May 15;94(4):227-34
pubmed: 10336238
Expert Opin Emerg Drugs. 2007 Mar;12(1):97-112
pubmed: 17355216
Neuroscience. 1997 Apr;77(4):1123-35
pubmed: 9130792
Stroke. 2016 Sep;47(9):2355-9
pubmed: 27462118
Stroke. 2000 Jun;31(6):1234-9
pubmed: 10835438
Curr Drug Targets CNS Neurol Disord. 2005 Feb;4(1):51-61
pubmed: 15723613
Stroke. 2004 Jan;35(1):179-84
pubmed: 14657453
Stroke. 1989 Sep;20(9):1143-9
pubmed: 2672425
Stroke. 2009 Dec;40(12):3796-803
pubmed: 19875736
Biomol Ther (Seoul). 2017 Mar 1;25(2):149-157
pubmed: 27530114
Stroke. 1997 May;28(5):1060-5
pubmed: 9158650
Stroke. 1997 Feb;28(2):428-32
pubmed: 9040701
Cerebrovasc Dis. 1998 May-Jun;8(3):172-81
pubmed: 9619701
Stroke. 2002 May;33(5):1424-7
pubmed: 11988626
J Neurochem. 1996 Jan;66(1):421-4
pubmed: 8522983
J Neuroinflammation. 2018 Jul 3;15(1):195
pubmed: 29970193
Medicine (Baltimore). 2016 Mar;95(13):e3186
pubmed: 27043681
Med Sci Monit Basic Res. 2013 Jan 28;19:37-45
pubmed: 23353570
Ann N Y Acad Sci. 1995 Sep 15;765:328-9
pubmed: 7486634
Pathophysiology. 2010 Jun;17(3):197-218
pubmed: 20074922
Oxid Med Cell Longev. 2015;2015:964518
pubmed: 26576229
Neurosci Lett. 2001 Jun 1;305(1):41-4
pubmed: 11356303
Stroke. 2001 Aug;32(8):1906-11
pubmed: 11486124
Cochrane Database Syst Rev. 2002;(1):CD001924
pubmed: 11869612
Science. 1989 Jun 16;244(4910):1360-2
pubmed: 2660263
Stroke. 2009 Apr;40(4):1082-90
pubmed: 19211488
Circulation. 2015 Sep 22;132(12):1104-1112
pubmed: 26202811
N Engl J Med. 1995 Dec 14;333(24):1581-7
pubmed: 7477192
Brain Res. 1991 May 10;548(1-2):242-7
pubmed: 1678297
Lancet. 2012 Jul 28;380(9839):349-57
pubmed: 22691567
Pharmacology. 2013;92(5-6):324-34
pubmed: 24356194
Stroke. 2012 Mar;43(3):630-6
pubmed: 22282884
Exp Ther Med. 2015 Jul;10(1):133-138
pubmed: 26170924
Brain Res. 2000 Apr 17;862(1-2):59-62
pubmed: 10799669
Stroke. 2008 Jan;39(1):87-99
pubmed: 18032739
CMAJ. 2015 Sep 8;187(12):887-93
pubmed: 26243819
Neuroreport. 1993 Sep 30;4(12):1339-42
pubmed: 7903166
Stroke. 2002 Mar;33(3):831-6
pubmed: 11872911
J Neurochem. 2012 Oct;123(2):217-25
pubmed: 22845688
J Neurosci. 2000 May 1;20(9):3175-81
pubmed: 10777781
Ann N Y Acad Sci. 1995 Sep 15;765:315-6
pubmed: 7486627
Mol Neurodegener. 2011 Jan 25;6(1):11
pubmed: 21266064
Brain Res. 1992 Mar 6;574(1-2):171-7
pubmed: 1386274
Stroke. 2014 Dec;45(12):3618-24
pubmed: 25378424
Neuron. 2015 Jul 15;87(2):297-309
pubmed: 26182415
Stroke. 1984 Jul-Aug;15(4):679-85
pubmed: 6464060
Stroke. 2019 Mar;50(3):652-658
pubmed: 30741623
Eur J Pharmacol. 1998 Jul 3;352(1):29-35
pubmed: 9718264
Br J Pharmacol. 2007 Aug;151(8):1377-84
pubmed: 17603558
Neurosci Lett. 2016 Oct 28;633:7-13
pubmed: 27589890
Stroke. 1999 Jan;30(1):21-8
pubmed: 9880383
J Stroke Cerebrovasc Dis. 2016 Aug;25(8):1984-96
pubmed: 27234918
eNeuro. 2018 Apr 18;5(2):
pubmed: 29766045
J Neurol Sci. 2011 Feb 15;301(1-2):66-70
pubmed: 21094956
Stroke. 2000 Sep;31(9):2257-65
pubmed: 10978061
CNS Drug Rev. 2002 Winter;8(4):353-60
pubmed: 12481191
Br J Pharmacol. 2002 Jan;135(1):103-12
pubmed: 11786485
Stroke. 2003 Jun;34(6):1533-8
pubmed: 12738895
Int J Neurosci. 2015;125(12):918-23
pubmed: 25375267
Stroke. 1988 Apr;19(4):447-54
pubmed: 3363573
Curr Neuropharmacol. 2017;15(6):815-830
pubmed: 27964703
Brain Sci. 2013 Sep 23;3(3):1395-414
pubmed: 24961534
Brain Res. 2000 Nov 10;883(1):41-50
pubmed: 11063986
Expert Rev Cardiovasc Ther. 2010 Apr;8(4):593-603
pubmed: 20397832
J Neurosci. 2015 Jan 21;35(3):1250-9
pubmed: 25609639
Stroke. 2001 Feb;32(2):570-6
pubmed: 11157199
Neurol Res. 2014 Jan;36(1):65-9
pubmed: 24074041
Curr Med Res Opin. 2002;18 Suppl 2:s9-13
pubmed: 12365832
J Neurointerv Surg. 2014 Mar;6(2):91-5
pubmed: 23468538
CNS Drug Rev. 2002 Winter;8(4):337-52
pubmed: 12481190
Genes (Basel). 2017 Feb 27;8(3):
pubmed: 28264471
Stroke. 2003 Jul;34(7):1790-5
pubmed: 12805500
J Exp Stroke Transl Med. 2009 Jan 1;2(2):2-27
pubmed: 20369026
J Cereb Blood Flow Metab. 2005 Apr;25(4):451-9
pubmed: 15674237
Pharmacol Biochem Behav. 2001 Mar;68(3):443-7
pubmed: 11325397
CNS Drug Rev. 2005 Winter;11(4):379-402
pubmed: 16614737
Stroke. 2007 Feb;38(2):388-94
pubmed: 17204689
Exp Neurol. 2000 Feb;161(2):733-9
pubmed: 10686092
Biomed Res Int. 2017;2017:4863079
pubmed: 28286764
Neural Regen Res. 2014 Dec 1;9(23):2026-8
pubmed: 25657711
Brain Sci. 2015 Apr 30;5(2):165-77
pubmed: 25942688