New goals in ischemic stroke therapy: The experimental approach - Harmonizing science with practice

Cerebrovascular Diseases

Volumn 20, Issue SUPPL. 2, 2005, Pages 159-168

  Alonso De Leciñana, María ^a   Díez Tejedor, Exuperio ^b   Gutierrez, María ^b   Guerrero, Sandra ^b   Carceller, Fernando ^b   Roda, Jose María ^b  

^a HOSPITAL RAMÓN Y CAJAL   (Spain)

^b HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

Author keywords

Animal models; Experimental brain ischemia; Neuroprotection; Neurorestoration; Stroke therapy

Indexed keywords

6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; [1,2,3,4 TETRAHYDRO 7 (1H IMIDAZOL 1 YL) 6 NITRO 2,3 DIOXO 1 QUINOXALINYL]ACETIC ACID; ABCIXIMAB; ALTEPLASE; AMINO ACID RECEPTOR BLOCKING AGENT; ANTIBODY; ARGATROBAN; CALCIUM ANTAGONIST; CASPASE INHIBITOR; CD18 ANTIBODY; CITICOLINE; CLOMETHIAZOLE; CYCLOHEXIMIDE; DESMOTEPLASE; DIZOCILPINE; EPTIFIBATIDE; FIBRINOGEN RECEPTOR ANTAGONIST; FIBRINOLYTIC AGENT; LUBELUZOLE; NEUROPROTECTIVE AGENT; TIRILAZAD; UNCLASSIFIED DRUG;

BLOOD CLOT LYSIS; BRAIN INFARCTION; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CLINICAL RESEARCH; CONFERENCE PAPER; COST EFFECTIVENESS ANALYSIS; DRUG EFFICACY; FIBRINOLYTIC THERAPY; HUMAN; METHODOLOGY; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REPERFUSION; STEM CELL TRANSPLANTATION; CLINICAL TRIAL; RESEARCH; REVIEW; SPECIES DIFFERENCE;

BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CLINICAL TRIALS; HUMANS; RESEARCH; SPECIES SPECIFICITY; THROMBOLYTIC THERAPY;

EID: 33644796139     PISSN: 10159770     EISSN: None     Source Type: Journal    
DOI: 10.1159/000089370     Document Type: Conference Paper

References (100)

1. Siesjö BK: Pathophysiology and treatment of focal cerebral ischemia. I. Pathophysiology. J Neurosurg 1992;77:169-184.
2. Siesjö BK: Pathophysiology and treatment of focal cerebral ischemia. II. Mechanisms of damage and treatment. J Neurosurg 1992;77:337-354.
3. García JH, Wagner S, Liu KF, Hu XJ: Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 1995;26:627-635.
4. Astrup J, Siesjö BK, Symon L: Threshold in cerebral ischemia. The ischemic penumbra. Stroke 1981;12:723-727.
5. Hossmann KA: Viability thresholds and the penumbra of focal ischemia. Ann Neurol 1994;36:557-565.
6. Baron JC: Perfusion thresholds in human cerebral ischemia: historical perspective and therapeutic implications. Cerebrovasc Dis 2001;11(suppl 1):2-8.
7. Ginsberg MD: Injury mechanisms in the ischemic penumbra. Approaches to neuroprotection in acute ischemic stroke. Cerebrovasc Dis 1997;7(suppl 2):7-12.
8. Castillo J, Álvarez-Sabín J, Dávalos A, Díez-Tejedor E: Lizasoain I, Martínez-Vila E, Vivancos J, Zarranz JJ: Consensus review. Pharmacological neuroprotection in cerebral ischemia: is it still a therapeutic option? Neurología 2003;18:368-384.
9. Martínez-Vila E, Sieira PI: Current status and perspectives of neuroprotection in ischemic stroke treatment. Cerebrovasc Dis 2001;11(suppl 1):60-70.
10. The Internet Stroke Center: Washington University in St Louis. Clinical Trials Directory. http://www.strokecenter.org/trials/index_cats.htm.
11. Indredavik B, Bakke F, Solberg R, Rokseth R, Haaheim LL, Holme I: Benefit of a stroke unit: a randomized controlled trial. Stroke 1991;22:1026-1031.
12. Stroke Unit Trialist's Collaboration: Organised inpatient (stroke unit) care for stroke. The Cochrane Library, issue 2, 2003. Oxford: Update Software.
13. The National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587.
14. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P: Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998;352:1245-1251.
15. Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, Broderick JP, et al: Early stroke treatment associated with better outcome: the NINDS rt-PA Stroke Study. Neurology 2000;55:1649-1655.
16. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, et al, ATLANTIS Trials Investigators, ECASS Trials Investigators, NINDS rt-PA Study Group Investigators: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768-774.
17. Mohr JP, Orgogozo JM, Hennerici M: Meta-analysis of oral nimodipine trials in acute ischemic stroke. Cererbovasc Dis 1994;4:197-203.
18. Horn J, Limburg M, Vermeulen M: VENUS-Very Early Nimodipine Use in Stroke: final results from a randomized placebo-controlled trial. Cerebrovasc Dis 1999;9(suppl 1):127.
19. Muir KW, Lees KR: Excitatory amino acid antagonists for acute stroke. Cochrane Database Syst Rev 2003;(3):CD001244.
20. Gandolfo C, Sandercock P, Conti M: Lubeluzole for acute ischaemic stroke. Cochrane Database Syst Rev 2002;(1):CD001924.
21. Muir KW, Lees KR, Ford I, Davis S, Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators: Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 2004;363:439-445.
22. Ogawa A, Yoshimoto T, Kikuchi H, Sano K, Saito I, Yamaguchi T, Yasuhara H: EBSELEN in acute middle cerebral artery occlusion: a placebo-controlled, double-blind clinical trial. Cerebrovasc Dis 1999;9:112-118.
23. Ricci S, Celani MG, Cantisani AT, Righetti E: Piracetam for acute ischaemic stroke. Cochrane Database Syst Rev 2002;(4):CD000419.
24. Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, vanErven PM, Ahswood T, for the CLASS Study Group: Clomethiazole Acute Stroke Study (CLASS). Results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 1999;30:21-28.
25. Lyden P, Shuaib A, Lerin K and the Clomethiazole Acute Stroke Study Collaborative Group: The Clomethiazole Acute Stroke Study in ischemic stroke (CLASS I). Final results. Stroke 2002;35:122-129.
26. Clark WM, Warach SJ, Pettigrew LC, Gammans RE, Sabounjian LA: A randomized dose-response trial of citicoline in acute ischemic stroke patients. Neurology 1997;49:671-678.
27. Clark WM, Williams BJ, Selzer KA, Zweifler RM, Sabounjian LA, Gammans RE: A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Citicoline Stroke Study Group. Stroke 1999;30:2592-2597.
28. Clark WM, Weschler LR, Sabounjian LA, Schwiderski UE, for the Citicoline Stroke Study Group: A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001;57:1595-1602.
29. Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian LA, et al: Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 2000;48:713-722.
30. Dávalos A, Castillo J, Alvarez-Sabin J, Secades JJ, Mercader J, López S, Cobo E, Warach S, Sherman D, Clark WM, Lozano R: Oral citicoline in acute ischemic stroke. An individual patient data pooling analysis of clinical trials. Stroke 2002;33:2850-2857.
31. Alonso de Leciñana M, Díez-Tejedor E, Carceller F: Cerebral ischemia: from animal studies to clinical practice. Should the methods be reviewed? Cerebrovasc Dis 2001;11(suppl 1):20-30.
32. Gladstone DJ, Black SE, Hakim AM, for the Heart and Stroke Foundation of Ontario Centre of Excellence in Stroke Recovery: Toward wisdom from failure. Lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 2002;33:2123-2136.
33. Fisher M, Brott TG: Emerging therapies for acute ischemic stroke. New therapies on trial. Stroke 2003;34:359-361.
34. Grotta JC: Acute stroke therapy at the millennium: consummating the marriage between the laboratory and the bedside. The Feinberg lecture. Stroke 1999;30:1722-1728.
35. Fisher M, for the Stroke Therapy Academis Industry Roundtable: Recommendations for advancing development of acute stroke therapies. Stroke Therapy Academic Industry Roundtable 3. Stroke 2003;34:1539-1546.
36. McCann UD, Ricaurte GA: Caveat emptor: Editors beware. Neuropsycopharmacology 2001;24:333-334.
37. Ransom BR, Acharya AB, Goldberg MP: Molecular pathophysiology of white matter anoxic-ischemic injury; in Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds): Stroke: Pathophysiology, Diagnosis and Management. Philadelphia, Churchill Livingstone, 2004, pp 867-881.
38. Tamura A, Graham DI, McCulloch J, Teasdale GM: Focal cerebral ischemia in the rat. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1981;1:53-60.
39. Roda JM, Carceller F, Diez-Tejedor E, Avendaño C: Reduction of infarct size by intra-arterial nimodipine administered at reperfusion in a rat model of partially reversible brain focal ischemia. Stroke 1995;26:1888-1892.
40. Koizumi J, Yoshida Y, Nakazawa T, Oneda G: Experimental studies of ischemic brain edema 1. A new experimental model of cerebral embolism in rats in which recirculation can be reintroduced in the ischemic area. Jpn J Stroke 1986;8:1-8.
41. Overgaard K, Sereghy T, Boysen G, Pedersen H, Hoyer S, Diemer NH: A rat model of reproducible cerebral infarction using thrombotic blood clot emboli. J Cereb Blood Flow Metab 1992;12:484-490.
42. Alonso de Leciñana M, Díez-Tejedor E, Carceller F, Vega A, Roda JM: Advantages of associate inhibitors of ischemia reperfusion injury to intravenous thrombolysis for treatment of focal cerebral ischemia. Description of an experimental model. Rev Neurol 1996;24:207-213.
43. Jonas S, Aiyagari V, Vieira D, Figueroa M: The failure of neuronal protective agents versus the success of thrombolysis for the treatment of ischemic stroke. The predictive value of animal models. Ann NY Acad Sci 2001;939:257-267.
44. Heiss WD, Thiel A, Ground M, Graf R: Which targets are relevant for therapy of acute ischemic stroke? Stroke 1999;30:1486-1489.
45. Sobrado M, López M, Carceller F, García A, Roda JM: Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia. Neuroscience 2003;118:107-113.
46. Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R: CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 2002;42:846-854.
47. Corbett D, Nurse S: The problem of assessing affective neuroprotection in experimental cerebral ischemia. Prog Neurobiol 1998;54:531-548.
48. Rogers DC, Campbell CA, Stretton JL, Mackay KB: Correlation between motor impairment and infarct volume after permanent and transient middle cerebral artery occlusion in the rat. Stroke 1997;28:2060-2066.
49. Yonemori F, Yamaguchi T, Yamada H, Tamura A: Evaluation of a motor deficit after chronic focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1998;18:1099-1106.
50. Virley D, Beech JS, Smart SC, Williams SCR, Hodges H, Hunter AJ: A temporal MRI assessment of neuropathology after transient middle cerebral artery occlusion in the rat: correlation with behaviour. J Cereb Blood Flow Metab 2000;20:563-582.
51. Zhang L, Chen J, Li Y, Zhang ZG, Chopp M: Quantitative measurement of motor and somatosensory impairments in mild (30 min) and severe (2 h) transient middle cerebral artery occlusion in rats. J Neuol Sci 2000;174:141-146.
52. García JH, Liu KF, Ho KL: Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 1995;26:636-643.
53. Colbourne F, Li H, Buchan AM, Clemens JA: Continuing postischemic neuronal death in CAl: influence of ischemic duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 1999;30:662-668.
54. Zukin RS, Jover T, Yokota H, Calderone A, Simonescu M, Lau G: Molecular and cellular mechanisms of ischemia induced neuronal death; in Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds): Stroke: Pathophysiology, Diagnosis and Management. Philadelphia, Churchill Livingstone, 2004, pp 829-854.
55. Dyker AG, Lees KR: Duration of neuroprotective treatment for ischemic stroke. Stroke 1998;29:593-603.
56. Albers GW, Golberg MP, Choi DW: Do NMDA antagonists prevent neuronal injury? Yes. Arch Neurol 1992;49:418-420.
57. Iadecola C, Cho S, Feuerstein GZ, Hallenbeck J: Cerebral ischemia and inflammation; in Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds): Stroke: Pathophysiology, Diagnosis and Management. Philadelphia, Churchill Livingstone, 2004, pp 883-893.
58. Dalkara T, Moskowitz MA: Apoptosis in cerebral ischemia; in Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds): Stroke: Pathophysiology, Diagnosis and Management. Philadelphia, Churchill Livingstone, 2004, pp 855-866.
59. Schramm P, Schellinger PD, Klotz E, Kallenberg K, Fiebach JB, Külkens S, Heiland S, Knauth M, Sartor K: Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion weighted imaging and diffusion weighted imaging in patients with acute stroke of less than 6 h duration. Stroke 2004;35:1652-1658.
60. DEFUSE Study: Diffusion-weighted imaging Evaluation For Understanding Stroke Evolution. http://www.strokecenter.org/trials/updates.aspx.
61. Butcher KS, for the EPITHET Investigators: EPITHET: Echoplanar Imaging Thrombolysis Evaluation Trial. Presented at Clinical Trials session, 28th International Stroke Conference. Phoenix, Arizona, February 2003. http://www.astn.org.au/epithet/.
62. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S, DIAS Study Group: The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005;36:66-73.
63. Furlan A, for the DEDAS study group: Dose escalation study of desmoteplase in acute ischemic stroke (DEDAS). Presented at the 2005 International Stroke Conference. February 2005. http://www.strokecenter.org/ trials/TrialDetail.aspx?tid=470.
64. Alexandrov AV, Grotta JC: Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology 2002;59:862-867.
65. Adams HP, Brott T, Furlan AJ, Gómez CR, Grotta J, Helgason CM, Kwiatowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W: Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the stroke council, AHA. Stroke 1996;27:1711-1718.
66. Levy DE, Brott TG, Haley EC Jr, Marler JR, Sheppard GL, Barsan W, Broderick JP: Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke. Stroke 1994;25:291-297.
67. Lewandowsky CA, Frankel M, Tomsick TA, Broderick J, Frey J, Clark W, Starkman S, Grotta J, Spilker J, Khoury J, Brott T and the EMS Brinding Trial Investigators: Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke. Emergency Management of Stroke (EMS) Bridging Trial. Stroke 1999;30:2598-2605.
68. Tomsick T, Broderick P, Pancioli AM, Jauch E, Woo D, Kissela BM, Kanter D, Spilker J, Carrozzella J, Ernst T, Gaskill-Shipley M, Cornelius R: Combined IV-IA treatment in major acute ischemic stroke. Stroke 2002;35:359.
69. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moye LA, Hill MD, Wojner AW, CLOTBUST Investigators: Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004;351:2170-2178.
70. Starkman S, on behalf of the MERCI investigators: Results of the combined MERCI I-II (Mechanical Embolus Removal in Cerebral Ischemia) Trials. Stroke 2004;35:240.
71. Morris DC, Mitsias P, Silver B, Zhang Li, Daley S, Lewandowski C, Patel S, Lu M, Ford H: Abciximab and rt-PA in Acute Ischemic Stroke Treatment. Presented at the Ongoing Clinical Trials session, 28th International Stroke Conference, Phoenix, Arizona, February 2003. http://www.strokecenter.org/trials/ TrialDetail.aspx?tid=481.
72. The Clear Stroke Trial Investigators, Pancioli AM, Brodericl JP: Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke: The CLEAR Stroke Trial. Presented at the Ongoing Clinical Trials session, 29th International Stroke Conference. San Diego, California, 2004. http://www.strokecenter.org/trials/TrialDetail.aspx?tid=478.
73. th International Stroke Conference. San Diego, California, 2004. http://www.strokecenter.org/trials/TrialDetail.aspx?tid=566.
74. Lapchak PA, Chapman DF, Zivin JA: Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke. Stroke 2000;31:3034-3040.
75. Overgaard K, Sereghy T, Pedersen H, Boysen G: Neuroprotection with NBQX and thrombolysis with rt-PA in rat embolic stroke model. Neurol Res 1993;15:344-349.
76. Sereghy T, Overgaard K, Boysen G: Neuroprotection by excitatory aminoacid antagonist augments the benefit of thrombolysis in embolic stroke in rats. Stroke 1993;24:1702-1708.
77. Meden P, Overgaard K, Pedersen H, Boysen G: Effect of early treatment with tirilazad (U7400F) combined with delayed thrombolytic therapy in rat embolic stroke. Cerebrovasc Dis 1996;6:141-148.
78. Andersen M, Overgaard K, Meden P, Boysen G: Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 1999;30:1464-1471.
79. Zivin J, Mazzarella V: Tissue plasminogen activator plus glutamate antagonists improves outcome after embolic stroke. Arch Neurol 1991;48:1235-1238.
80. Zhang RL, Zhang ZG, Chopp M: Increased therapeutic efficacy with rt-PA and anti-CD18 antibody treatment of stroke in the rtA. Neurology 1999;52:273-279.
81. Grotta J, for the Combination Therapy Stroke Trial Investigators: Combination therapy stroke trial: recombinant tissue plasminogen activator with/without lubeluzole. Cerebrovasc Dis 2001;12:258-263.
82. Lyden P, Jacoby M, Schim J, Albers G, Mazzeo P, Ashwood T, Nordlund A, Odergren T: The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. Neurology 2001;57:1199-1205.
83. Peterson C, Prince HC, Williams B, Tempel D, Grotta JC: ARTIST+: AMPA Receptor Antagonist Treatment in Ischemic Stroke Trial, YM872 + Alteplase. Presented at the Ongoing Clinical Trials Session, 27th International Stroke Conference. San Antonio, Texas, February 2002. http://www.strokecenter.org/ trials/TrialDetail.aspx?tid=253.
84. Gutierrez M, Alonso de Leciñana M, Roda JM, Carceller F, Diez Tejedor E: Effect of citicoline, iv thrombolysis (rtPA) and its combination in an experimental model of embolic ischemic stroke in rat. Neurologia 2003;18:534.
85. Díez Tejedor E, Gutierrez M, Carceller F, Roda JM, Alonso de Leciñana M: Treatment with reperfusion and neuroprotection with low and high dose of citicoline in an experimental model focal cerebral ischemia. Which is the best? Cerebrovasc Dis 2004;17(suppl 5):67.
86. Onal MZ, Tatlisumak T, Sandage BW, Fisher M: Synergistic effects of citicoline and MK 801 in temporary experimental focal ischemia in rats. Stroke 1997;28:1065.
87. Uematsu D, Araki N, Greenberg JH, Sladky J, Reivich M: Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. Neurology 1991;41:88-94.
88. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Releu HJ: Neuroprotective effects of combination therapy with tirilazad and magnesium in rats subjected to reversible focal cerebral ischemia. Neurosurgery 1999;44:163-171.
89. Schabitz WR, Li F, Irie K, Sandage BW, Locke KW, Fisher M: Synergistic effects of a combination of low dose bFGF and citicoline after temporary experimental focal ischemia. Stroke 1999;30:427-432.
90. Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Baethmann A, Releu HJ: Combination drug therapy and mild hypothermia: a promising treatment strategy for reversible focal cerebral ischemia. Stroke 1999;30:1891-1899.
91. Linnik MD, Zobrist RH, Hatfield MD: Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats. Stroke 1993;24:2004-2008.
92. Ma J, Qiu J, Hirt L, Dalkara T, Moskowitz MA: Synergistic protective effect of caspase inhibitors and bFGF against brain injury induced by transient focal ischemia. Br J Pharmacol 2001;133:345-350.
93. Du C, Hu R, Csernansky CA, Liu XZ, Hsu CY, Choi DW: Additive neuroprotective effects of dextrorfan and cycloheximide in rats subjected to transient focal cerebral ischemia. Brain Res 1996;718:233-236.
94. Lee RG, van Donkelaar P: Mechanisms underlying functional recovery following stroke. Can J Neurol Sci 1995;22:257-263.
95. Li Y, Chen J, Chopp M: Cell proliferation and differentiation from ependymal, subependymal and choroid plexus in response to stroke in rats. J Neurol Sci 2002;193:137-146.
96. Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M: Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001;32:1005-1011.
97. Li Y, Chen J, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M: Human marrow stromal cell therapy for stroke in rat. Neurotrophins and functional recovery. Neurology 2002;59:514-523.
98. Li Y, Chen J, Wang L, Lu M, Chopp M: Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001;56:1666-1672.
99. Modo M, Stroemer RP, Tang E, Patel S, Hodges H: Effects of implantation site of stem cell grafts on behavioral recovery from stroke damage. Stroke 2002;33:2270-2278.
100. Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M, Reitman MA, Bynum L: Transplantation of cultured human neuronal cells for patients with stroke. Neurology 2000;55:565-569.