Skip to main content
Erschienen in: Metabolic Brain Disease 2/2015

01.04.2015 | Original Paper

Improving the translation of animal ischemic stroke studies to humans

verfasst von: Glen C. Jickling, Frank R. Sharp

Erschienen in: Metabolic Brain Disease | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Despite testing more than 1,026 therapeutic strategies in models of ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendations and statements of RIGOR from the NIH/NINDS. In this commentary we discuss additional aspects that may be important to improve the translational success of ischemic stroke therapies. These include use of tissue plasminogen activator in animal studies; modeling ischemic stroke heterogeneity in terms of infarct size and cause of human stroke; addressing the confounding effect of anesthesia; use of comparable therapeutic dosage between humans and animals based on biological effect; modeling the human immune system; and developing outcome measures in animals comparable to those used in human stroke trials. With additional study and improved animal modeling of factors involved in human ischemic stroke, we are optimistic that new stroke therapies will be developed.
Literatur
Zurück zum Zitat Abou-Chebl A, Lin R, Hussain MS, Jovin TG, Levy EI, Liebeskind DS, Yoo AJ, Hsu DP, Rymer MM, Tayal AH, Zaidat OO, Natarajan SK, Nogueira RG, Nanda A, Tian M, Hao Q, Kalia JS, Nguyen TN, Chen M, Gupta R (2010) Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multicenter study. Stroke J Cereb Circ 41(6):1175–1179. doi:10.1161/STROKEAHA.109.574129 CrossRef Abou-Chebl A, Lin R, Hussain MS, Jovin TG, Levy EI, Liebeskind DS, Yoo AJ, Hsu DP, Rymer MM, Tayal AH, Zaidat OO, Natarajan SK, Nogueira RG, Nanda A, Tian M, Hao Q, Kalia JS, Nguyen TN, Chen M, Gupta R (2010) Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multicenter study. Stroke J Cereb Circ 41(6):1175–1179. doi:10.​1161/​STROKEAHA.​109.​574129 CrossRef
Zurück zum Zitat Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, Hurn P, Liebeskind DS, Nogueira RG, Saver JL, Consortium SV (2011) Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke J Cereb Circ 42(9):2645–2650. doi:10.1161/STROKEAHA.111.618850 CrossRef Albers GW, Goldstein LB, Hess DC, Wechsler LR, Furie KL, Gorelick PB, Hurn P, Liebeskind DS, Nogueira RG, Saver JL, Consortium SV (2011) Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies. Stroke J Cereb Circ 42(9):2645–2650. doi:10.​1161/​STROKEAHA.​111.​618850 CrossRef
Zurück zum Zitat Bailey EL, Wardlaw JM, Graham D, Dominiczak AF, Sudlow CL, Smith C (2011b) Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol 37(7):711–726. doi:10.1111/j.1365-2990.2011.01170.x CrossRefPubMed Bailey EL, Wardlaw JM, Graham D, Dominiczak AF, Sudlow CL, Smith C (2011b) Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol 37(7):711–726. doi:10.​1111/​j.​1365-2990.​2011.​01170.​x CrossRefPubMed
Zurück zum Zitat Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke J Cereb Circ 27(9):1616–1622, discussion 1623CrossRef Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke J Cereb Circ 27(9):1616–1622, discussion 1623CrossRef
Zurück zum Zitat Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA, Interventional Management of Stroke IIII (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. New Engl J Med 368(10):893–903. doi:10.1056/NEJMoa1214300 CrossRefPubMedCentralPubMed Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, Jauch EC, Jovin TG, Yan B, Silver FL, von Kummer R, Molina CA, Demaerschalk BM, Budzik R, Clark WM, Zaidat OO, Malisch TW, Goyal M, Schonewille WJ, Mazighi M, Engelter ST, Anderson C, Spilker J, Carrozzella J, Ryckborst KJ, Janis LS, Martin RH, Foster LD, Tomsick TA, Interventional Management of Stroke IIII (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. New Engl J Med 368(10):893–903. doi:10.​1056/​NEJMoa1214300 CrossRefPubMedCentralPubMed
Zurück zum Zitat Chapman DF, Lyden P, Lapchak PA, Nunez S, Thibodeaux H, Zivin J (2001) Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model. Stroke J Cereb Circ 32(3):748–752CrossRef Chapman DF, Lyden P, Lapchak PA, Nunez S, Thibodeaux H, Zivin J (2001) Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model. Stroke J Cereb Circ 32(3):748–752CrossRef
Zurück zum Zitat Davis MJ, Menon BK, Baghirzada LB, Campos-Herrera CR, Goyal M, Hill MD, Archer DP, Calgary Stroke P (2012) Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology 116(2):396–405. doi:10.1097/ALN.0b013e318242a5d2 CrossRefPubMed Davis MJ, Menon BK, Baghirzada LB, Campos-Herrera CR, Goyal M, Hill MD, Archer DP, Calgary Stroke P (2012) Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology 116(2):396–405. doi:10.​1097/​ALN.​0b013e318242a5d2​ CrossRefPubMed
Zurück zum Zitat Fearon P, McArthur KS, Garrity K, Graham LJ, McGroarty G, Vincent S, Quinn TJ (2012) Prestroke modified rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting. Stroke J Cereb Circ 43(12):3184–3188. doi:10.1161/STROKEAHA.112.670422 CrossRef Fearon P, McArthur KS, Garrity K, Graham LJ, McGroarty G, Vincent S, Quinn TJ (2012) Prestroke modified rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting. Stroke J Cereb Circ 43(12):3184–3188. doi:10.​1161/​STROKEAHA.​112.​670422 CrossRef
Zurück zum Zitat Feuerstein GZ, Zaleska MM, Krams M, Wang X, Day M, Rutkowski JL, Finklestein SP, Pangalos MN, Poole M, Stiles GL, Ruffolo RR, Walsh FL (2008) Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 28(1):217–219. doi:10.1038/sj.jcbfm.9600516 CrossRef Feuerstein GZ, Zaleska MM, Krams M, Wang X, Day M, Rutkowski JL, Finklestein SP, Pangalos MN, Poole M, Stiles GL, Ruffolo RR, Walsh FL (2008) Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 28(1):217–219. doi:10.​1038/​sj.​jcbfm.​9600516 CrossRef
Zurück zum Zitat Fisher M, Albers GW, Donnan GA, Furlan AJ, Grotta JC, Kidwell CS, Sacco RL, Wechsler LR, Stroke Therapy Academic Industry Roundtable IV (2005) Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable. Stroke J Cereb Circ 36(8):1808–1813. doi:10.1161/01.STR.0000173403.60553.27 CrossRef Fisher M, Albers GW, Donnan GA, Furlan AJ, Grotta JC, Kidwell CS, Sacco RL, Wechsler LR, Stroke Therapy Academic Industry Roundtable IV (2005) Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable. Stroke J Cereb Circ 36(8):1808–1813. doi:10.​1161/​01.​STR.​0000173403.​60553.​27 CrossRef
Zurück zum Zitat Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH, Group S (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke J Cereb Circ 40(6):2244–2250. doi:10.1161/STROKEAHA.108.541128 CrossRef Fisher M, Feuerstein G, Howells DW, Hurn PD, Kent TA, Savitz SI, Lo EH, Group S (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke J Cereb Circ 40(6):2244–2250. doi:10.​1161/​STROKEAHA.​108.​541128 CrossRef
Zurück zum Zitat Fox JG (1985) Laboratory-animal medicine changes and challenges. Cornell Vet 75(1):159–170PubMed Fox JG (1985) Laboratory-animal medicine changes and challenges. Cornell Vet 75(1):159–170PubMed
Zurück zum Zitat Gakuba C, Gauberti M, Mazighi M, Defer G, Hanouz JL, Vivien D (2011) Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation. Stroke J Cereb Circ 42(10):2947–2949. doi:10.1161/STROKEAHA.111.620468 CrossRef Gakuba C, Gauberti M, Mazighi M, Defer G, Hanouz JL, Vivien D (2011) Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation. Stroke J Cereb Circ 42(10):2947–2949. doi:10.​1161/​STROKEAHA.​111.​620468 CrossRef
Zurück zum Zitat Gelb AW, Bayona NA, Wilson JX, Cechetto DF (2002) Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 96(5):1183–1190CrossRefPubMed Gelb AW, Bayona NA, Wilson JX, Cechetto DF (2002) Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 96(5):1183–1190CrossRefPubMed
Zurück zum Zitat Ginsberg MD, Palesch YY, Hill MD, Martin RH, Moy CS, Barsan WG, Waldman BD, Tamariz D, Ryckborst KJ, Alias, Neurological Emergencies Treatment Trials I (2013) High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurol 12(11):1049–1058. doi:10.1016/S1474-4422(13)70223-0 CrossRefPubMedCentralPubMed Ginsberg MD, Palesch YY, Hill MD, Martin RH, Moy CS, Barsan WG, Waldman BD, Tamariz D, Ryckborst KJ, Alias, Neurological Emergencies Treatment Trials I (2013) High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurol 12(11):1049–1058. doi:10.​1016/​S1474-4422(13)70223-0 CrossRefPubMedCentralPubMed
Zurück zum Zitat Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D, E Investigators (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. New Engl J Med 359(13):1317–1329. doi:10.1056/NEJMoa0804656 CrossRefPubMed Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D, E Investigators (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. New Engl J Med 359(13):1317–1329. doi:10.​1056/​NEJMoa0804656 CrossRefPubMed
Zurück zum Zitat Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 28(12):1877–1891. doi:10.1038/jcbfm.2008.91 CrossRef Hainsworth AH, Markus HS (2008) Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 28(12):1877–1891. doi:10.​1038/​jcbfm.​2008.​91 CrossRef
Zurück zum Zitat Head BP, Patel P (2007) Anesthetics and brain protection. Curr Opin Anaesthesiol 20(5):395–399CrossRefPubMed Head BP, Patel P (2007) Anesthetics and brain protection. Curr Opin Anaesthesiol 20(5):395–399CrossRefPubMed
Zurück zum Zitat Henninger N, Sicard KM, Schmidt KF, Bardutzky J, Fisher M (2006) Comparison of ischemic lesion evolution in embolic versus mechanical middle cerebral artery occlusion in Sprague Dawley rats using diffusion and perfusion imaging. Stroke J Cereb Circ 37(5):1283–1287. doi:10.1161/01.STR.0000217223.72193.98 CrossRef Henninger N, Sicard KM, Schmidt KF, Bardutzky J, Fisher M (2006) Comparison of ischemic lesion evolution in embolic versus mechanical middle cerebral artery occlusion in Sprague Dawley rats using diffusion and perfusion imaging. Stroke J Cereb Circ 37(5):1283–1287. doi:10.​1161/​01.​STR.​0000217223.​72193.​98 CrossRef
Zurück zum Zitat Hossmann KA (2012) The two pathophysiologies of focal brain ischemia: implications for translational stroke research. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 32(7):1310–1316. doi:10.1038/jcbfm.2011.186 CrossRef Hossmann KA (2012) The two pathophysiologies of focal brain ischemia: implications for translational stroke research. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 32(7):1310–1316. doi:10.​1038/​jcbfm.​2011.​186 CrossRef
Zurück zum Zitat Hsia AW, Sachdev HS, Tomlinson J, Hamilton SA, Tong DC (2003) Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter? Neurology 61(1):71–75CrossRefPubMed Hsia AW, Sachdev HS, Tomlinson J, Hamilton SA, Tong DC (2003) Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter? Neurology 61(1):71–75CrossRefPubMed
Zurück zum Zitat Huybrechts KF, Caro JJ (2007) The Barthel Index and modified Rankin Scale as prognostic tools for long-term outcomes after stroke: a qualitative review of the literature. Curr Med Res Opin 23(7):1627–1636. doi:10.1185/030079907X210444 CrossRefPubMed Huybrechts KF, Caro JJ (2007) The Barthel Index and modified Rankin Scale as prognostic tools for long-term outcomes after stroke: a qualitative review of the literature. Curr Med Res Opin 23(7):1627–1636. doi:10.​1185/​030079907X210444​ CrossRefPubMed
Zurück zum Zitat Jickling GC, Xu H, Stamova B, Ander BP, Zhan X, Tian Y, Liu D, Turner RJ, Mesias M, Verro P, Khoury J, Jauch EC, Pancioli A, Broderick JP, Sharp FR (2010) Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol 68(5):681–692. doi:10.1002/ana.22187 CrossRefPubMedCentralPubMed Jickling GC, Xu H, Stamova B, Ander BP, Zhan X, Tian Y, Liu D, Turner RJ, Mesias M, Verro P, Khoury J, Jauch EC, Pancioli A, Broderick JP, Sharp FR (2010) Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol 68(5):681–692. doi:10.​1002/​ana.​22187 CrossRefPubMedCentralPubMed
Zurück zum Zitat Karatas H, Erdener SE, Gursoy-Ozdemir Y, Gurer G, Soylemezoglu F, Dunn AK, Dalkara T (2011) Thrombotic distal middle cerebral artery occlusion produced by topical FeCl(3) application: a novel model suitable for intravital microscopy and thrombolysis studies. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 31(6):1452–1460. doi:10.1038/jcbfm.2011.8 CrossRef Karatas H, Erdener SE, Gursoy-Ozdemir Y, Gurer G, Soylemezoglu F, Dunn AK, Dalkara T (2011) Thrombotic distal middle cerebral artery occlusion produced by topical FeCl(3) application: a novel model suitable for intravital microscopy and thrombolysis studies. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 31(6):1452–1460. doi:10.​1038/​jcbfm.​2011.​8 CrossRef
Zurück zum Zitat Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL, MR Investigators (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. New Engl J Med 368(10):914–923. doi:10.1056/NEJMoa1212793 CrossRefPubMedCentralPubMed Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, Feng L, Meyer BC, Olson S, Schwamm LH, Yoo AJ, Marshall RS, Meyers PM, Yavagal DR, Wintermark M, Guzy J, Starkman S, Saver JL, MR Investigators (2013) A trial of imaging selection and endovascular treatment for ischemic stroke. New Engl J Med 368(10):914–923. doi:10.​1056/​NEJMoa1212793 CrossRefPubMedCentralPubMed
Zurück zum Zitat Kirsch JR, Traystman RJ, Hurn PD (1996) Anesthetics and cerebroprotection: experimental aspects. Int Anesthesiol Clin 34(4):73–93CrossRefPubMed Kirsch JR, Traystman RJ, Hurn PD (1996) Anesthetics and cerebroprotection: experimental aspects. Int Anesthesiol Clin 34(4):73–93CrossRefPubMed
Zurück zum Zitat Koerner IP, Brambrink AM (2006) Brain protection by anesthetic agents. Curr Opin Anaesthesiol 19(5):481–486CrossRefPubMed Koerner IP, Brambrink AM (2006) Brain protection by anesthetic agents. Curr Opin Anaesthesiol 19(5):481–486CrossRefPubMed
Zurück zum Zitat Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RJ, Fillit H, Finkelstein R, Fisher M, Gendelman HE, Golub RM, Goudreau JL, Gross RA, Gubitz AK, Hesterlee SE, Howells DW, Huguenard J, Kelner K, Koroshetz W, Krainc D, Lazic SE, Levine MS, Macleod MR, McCall JM, Moxley RT 3rd, Narasimhan K, Noble LJ, Perrin S, Porter JD, Steward O, Unger E, Utz U, Silberberg SD (2012) A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490(7419):187–191. doi:10.1038/nature11556 CrossRefPubMedCentralPubMed Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RJ, Fillit H, Finkelstein R, Fisher M, Gendelman HE, Golub RM, Goudreau JL, Gross RA, Gubitz AK, Hesterlee SE, Howells DW, Huguenard J, Kelner K, Koroshetz W, Krainc D, Lazic SE, Levine MS, Macleod MR, McCall JM, Moxley RT 3rd, Narasimhan K, Noble LJ, Perrin S, Porter JD, Steward O, Unger E, Utz U, Silberberg SD (2012) A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490(7419):187–191. doi:10.​1038/​nature11556 CrossRefPubMedCentralPubMed
Zurück zum Zitat Lansberg MG, Lee J, Christensen S, Straka M, De Silva DA, Mlynash M, Campbell BC, Bammer R, Olivot JM, Desmond P, Davis SM, Donnan GA, Albers GW (2011) RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study. Stroke J Cereb Circ 42(6):1608–1614. doi:10.1161/STROKEAHA.110.609008 CrossRef Lansberg MG, Lee J, Christensen S, Straka M, De Silva DA, Mlynash M, Campbell BC, Bammer R, Olivot JM, Desmond P, Davis SM, Donnan GA, Albers GW (2011) RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study. Stroke J Cereb Circ 42(6):1608–1614. doi:10.​1161/​STROKEAHA.​110.​609008 CrossRef
Zurück zum Zitat Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, Wilder MJ, Lutsep HL, Czartoski TJ, Bernstein RA, Chang CW, Warach S, Fazekas F, Inoue M, Tipirneni A, Hamilton SA, Zaharchuk G, Marks MP, Bammer R, Albers GW, investigators Ds (2012) MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 11(10):860–867. doi:10.1016/S1474-4422(12)70203-X CrossRefPubMedCentralPubMed Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, Wilder MJ, Lutsep HL, Czartoski TJ, Bernstein RA, Chang CW, Warach S, Fazekas F, Inoue M, Tipirneni A, Hamilton SA, Zaharchuk G, Marks MP, Bammer R, Albers GW, investigators Ds (2012) MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 11(10):860–867. doi:10.​1016/​S1474-4422(12)70203-X CrossRefPubMedCentralPubMed
Zurück zum Zitat Lapchak PA, Araujo DM, Pakola S, Song D, Wei J, Zivin JA (2002a) Microplasmin: a novel thrombolytic that improves behavioral outcome after embolic strokes in rabbits. Stroke J Cereb Circ 33(9):2279–2284CrossRef Lapchak PA, Araujo DM, Pakola S, Song D, Wei J, Zivin JA (2002a) Microplasmin: a novel thrombolytic that improves behavioral outcome after embolic strokes in rabbits. Stroke J Cereb Circ 33(9):2279–2284CrossRef
Zurück zum Zitat Lapchak PA, Araujo DM, Song D, Wei J, Zivin JA (2002b) Neuroprotective effects of the spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) in a rabbit small clot embolic stroke model: combination studies with the thrombolytic tissue plasminogen activator. Stroke J Cereb Circ 33(5):1411–1415CrossRef Lapchak PA, Araujo DM, Song D, Wei J, Zivin JA (2002b) Neuroprotective effects of the spin trap agent disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) in a rabbit small clot embolic stroke model: combination studies with the thrombolytic tissue plasminogen activator. Stroke J Cereb Circ 33(5):1411–1415CrossRef
Zurück zum Zitat Liou SY, Stringer F, Hirayama M (2012) The impact of pharmacogenomics research on drug development. Drug Metab Pharmacokinet 27(1):2–8CrossRefPubMed Liou SY, Stringer F, Hirayama M (2012) The impact of pharmacogenomics research on drug development. Drug Metab Pharmacokinet 27(1):2–8CrossRefPubMed
Zurück zum Zitat Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J Off Publ Fed Am Soc Exp Biol 22(3):659–661. doi:10.1096/fj.07-9574LSF Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J Off Publ Fed Am Soc Exp Biol 22(3):659–661. doi:10.​1096/​fj.​07-9574LSF
Zurück zum Zitat Rosell A, Agin V, Rahman M, Morancho A, Ali C, Koistinaho J, Wang X, Vivien D, Schwaninger M, Montaner J (2013) Distal occlusion of the middle cerebral artery in mice: are we ready to assess long-term functional outcome? Transl Stroke Res 4(3):297–307. doi:10.1007/s12975-012-0234-1 CrossRefPubMed Rosell A, Agin V, Rahman M, Morancho A, Ali C, Koistinaho J, Wang X, Vivien D, Schwaninger M, Montaner J (2013) Distal occlusion of the middle cerebral artery in mice: are we ready to assess long-term functional outcome? Transl Stroke Res 4(3):297–307. doi:10.​1007/​s12975-012-0234-1 CrossRefPubMed
Zurück zum Zitat Russell JC, Proctor SD (2006) Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis. Cardiovasc Pathol Off J Soc Cardiovasc Pathol 15(6):318–330. doi:10.1016/j.carpath.2006.09.001 CrossRef Russell JC, Proctor SD (2006) Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis. Cardiovasc Pathol Off J Soc Cardiovasc Pathol 15(6):318–330. doi:10.​1016/​j.​carpath.​2006.​09.​001 CrossRef
Zurück zum Zitat Saver JL, Albers GW, Dunn B, Johnston KC, Fisher M, Consortium SV (2009) Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke J Cereb Circ 40(7):2594–2600. doi:10.1161/STROKEAHA.109.552554 CrossRef Saver JL, Albers GW, Dunn B, Johnston KC, Fisher M, Consortium SV (2009) Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke J Cereb Circ 40(7):2594–2600. doi:10.​1161/​STROKEAHA.​109.​552554 CrossRef
Zurück zum Zitat Singh SS (2006) Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Current Drug Metab 7(2):165–182CrossRef Singh SS (2006) Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Current Drug Metab 7(2):165–182CrossRef
Zurück zum Zitat Stamova B, Xu H, Jickling G, Bushnell C, Tian Y, Ander BP, Zhan X, Liu D, Turner R, Adamczyk P, Khoury JC, Pancioli A, Jauch E, Broderick JP, Sharp FR (2010) Gene expression profiling of blood for the prediction of ischemic stroke. Stroke J Cereb Circ 41(10):2171–2177. doi:10.1161/STROKEAHA.110.588335 CrossRef Stamova B, Xu H, Jickling G, Bushnell C, Tian Y, Ander BP, Zhan X, Liu D, Turner R, Adamczyk P, Khoury JC, Pancioli A, Jauch E, Broderick JP, Sharp FR (2010) Gene expression profiling of blood for the prediction of ischemic stroke. Stroke J Cereb Circ 41(10):2171–2177. doi:10.​1161/​STROKEAHA.​110.​588335 CrossRef
Zurück zum Zitat Stroke Therapy Academic Industry R, II (2001) Recommendations for clinical trial evaluation of acute stroke therapies. Stroke J Cereb Circ 32(7):1598–1606CrossRef Stroke Therapy Academic Industry R, II (2001) Recommendations for clinical trial evaluation of acute stroke therapies. Stroke J Cereb Circ 32(7):1598–1606CrossRef
Zurück zum Zitat Takano K, Tatlisumak T, Bergmann AG, Gibson DG 3rd, Fisher M (1997) Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats. J Neurol Sci 153(1):8–11CrossRefPubMed Takano K, Tatlisumak T, Bergmann AG, Gibson DG 3rd, Fisher M (1997) Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats. J Neurol Sci 153(1):8–11CrossRefPubMed
Zurück zum Zitat Tang Y, Lu A, Aronow BJ, Sharp FR (2001) Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. Ann Neurol 50(6):699–707CrossRefPubMed Tang Y, Lu A, Aronow BJ, Sharp FR (2001) Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. Ann Neurol 50(6):699–707CrossRefPubMed
Zurück zum Zitat Tang Y, Xu H, Du X, Lit L, Walker W, Lu A, Ran R, Gregg JP, Reilly M, Pancioli A, Khoury JC, Sauerbeck LR, Carrozzella JA, Spilker J, Clark J, Wagner KR, Jauch EC, Chang DJ, Verro P, Broderick JP, Sharp FR (2006) Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 26(8):1089–1102. doi:10.1038/sj.jcbfm.9600264 CrossRef Tang Y, Xu H, Du X, Lit L, Walker W, Lu A, Ran R, Gregg JP, Reilly M, Pancioli A, Khoury JC, Sauerbeck LR, Carrozzella JA, Spilker J, Clark J, Wagner KR, Jauch EC, Chang DJ, Verro P, Broderick JP, Sharp FR (2006) Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 26(8):1089–1102. doi:10.​1038/​sj.​jcbfm.​9600264 CrossRef
Zurück zum Zitat Verbeuren TJ (2006) Experimental models of thrombosis and atherosclerosis. Therapie 61(5):379–387CrossRefPubMed Verbeuren TJ (2006) Experimental models of thrombosis and atherosclerosis. Therapie 61(5):379–387CrossRefPubMed
Zurück zum Zitat Wang L, Jing W, Hang YN (2008) Glutamate-induced c-Jun expression in neuronal PC12 cells: the effects of ketamine and propofol. J Neurosurg Anesthesiol 20(2):124–130CrossRefPubMed Wang L, Jing W, Hang YN (2008) Glutamate-induced c-Jun expression in neuronal PC12 cells: the effects of ketamine and propofol. J Neurosurg Anesthesiol 20(2):124–130CrossRefPubMed
Zurück zum Zitat Zhao H, Collier JM, Quah DM, Purvis T, Bernhardt J (2010) The modified Rankin Scale in acute stroke has good inter-rater-reliability but questionable validity. Cerebrovasc Dis 29(2):188–193. doi:10.1159/000267278 CrossRefPubMed Zhao H, Collier JM, Quah DM, Purvis T, Bernhardt J (2010) The modified Rankin Scale in acute stroke has good inter-rater-reliability but questionable validity. Cerebrovasc Dis 29(2):188–193. doi:10.​1159/​000267278 CrossRefPubMed
Zurück zum Zitat Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA (1985) Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science 230(4731):1289–1292CrossRefPubMed Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA (1985) Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science 230(4731):1289–1292CrossRefPubMed
Metadaten
Titel
Improving the translation of animal ischemic stroke studies to humans
verfasst von
Glen C. Jickling
Frank R. Sharp
Publikationsdatum
01.04.2015
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 2/2015
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-014-9499-2

Weitere Artikel der Ausgabe 2/2015

Metabolic Brain Disease 2/2015 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.