The Search for Neuroprotective Strategies in Stroke

American Journal of Neuroradiology

Volumn 25, Issue 2, 2004, Pages 181-194

  Danton, Gary H ^a   Dietrich, W Dalton ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (5 CHLORO 2 METHOXYPHENYL) 3 FLUORO 2,3 DIHYDRO 6 TRIFLUOROMETHYL 1H INDOL 2 ONE; 3,3 BIS(3 FLUOROPHENYL) N METHYLPROPYLAMINE; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; 4 PHOSPHONOMETHYLPIPECOLIC ACID; 6,7,8,9 TETRAHYDRO 9 (2 MORPHOLINOETHYL) 2,4 BIS(1 PYRROLIDINYL) 5H PYRIMIDO[4,5 B]INDOLE; [1,2,3,4 TETRAHYDRO 7 (1H IMIDAZOL 1 YL) 6 NITRO 2,3 DIOXO 1 QUINOXALINYL]ACETIC ACID; AMPA RECEPTOR AGONIST; ANTIINFLAMMATORY AGENT; APTIGANEL; BAY 367620; BB 1101; CALCIUM CHANNEL BLOCKING AGENT; DANTROLENE; DISUFENTON SODIUM; DIZOCILPINE; ELIPRODIL; EMOPAMIL; FIBRINOLYTIC AGENT; FLUNARIZINE; FOSPHENYTOIN SODIUM; GLUTAMATE RECEPTOR ANTAGONIST; GPI 5232; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; KB R7785; MAGNESIUM; MATRIX METALLOPROTEINASE INHIBITOR; MDL 74180; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROPROTECTIVE AGENT; NIMODIPINE; NORPHENAZONE; POTASSIUM CHANNEL STIMULATING AGENT; RILUZOLE; SCAVENGER; SIPATRIGINE; SODIUM CHANNEL BLOCKING AGENT; TISSUE PLASMINOGEN ACTIVATOR; TRAXOPRODIL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BRAIN BLOOD FLOW; BRAIN ISCHEMIA; CEREBROVASCULAR DISEASE; CLINICAL RESEARCH; CLINICAL TRIAL; DISEASE MODEL; DRUG EFFECT; DRUG EFFICACY; FIBRINOLYTIC THERAPY; HUMAN; INDUCED HYPOTHERMIA; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; PHYSICIAN; REVIEW; SIDE EFFECT; STROKE;

ANIMALS; BRAIN ISCHEMIA; CELL SURVIVAL; CEREBROVASCULAR ACCIDENT; CLINICAL TRIALS; DISEASE MODELS, ANIMAL; HUMANS; INFARCTION, MIDDLE CEREBRAL ARTERY; NEURONS; NEUROPROTECTIVE AGENTS;

EID: 1242339543     PISSN: 01956108     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (161)

1. Markgraf CG, Kraydieh S, Prado R, Watson BD, Dietrich WD, Ginsberg MD. Comparative histopathologic consequences of photothrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistar rats. Stroke 1993;24:286-292; discussion 292-293
2. Dictrich WD, Busto R, Bethca JR. Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats. Exp Neurol 1999;158:444-450
3. Dietrich WD, Nakayama H, Watson BD, Kanemitsu H. Morphological consequences of early reperfusion following thrombotic or mechanical occlusion of the rat middle cerebral artery. Acta Neuropathol (Berl) 1989;78:605-614
4. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. Middle cerebral artery occlusion in the rat by intraluminal suture: neurological and pathological evaluation of an improved model. Stroke 1996;27:1616-1622; discussion 1623
5. Watson BD, Dietrich WD, Prado R, Ginsberg MD. Argon laser-induced arterial photothrombosis: characterization and possible application to therapy of arteriovenous malformations. J Neurosurg 1987;66:748-754
6. Watson BD, Prado R, VeJoso A, Brunschwig JP, Dietrich WD. Cerebral blood flow restoration and reperfusion injury after ultraviolet laser-facilitated middle cerebral artery recanalization in rat thrombotic stroke. Stroke 2002;33:428-434
7. Danton GH, Prado R, Truettner J, Watson BD, Dietrich WD. Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats. J Cereb Blood Flow Metab 2002;22:612-619
8. Danton GH, Prado R, Watson BD, Dietrich WD. Temporal profile of enhanced vulnerability of the postthrombotic brain to secondary embolic events. Stroke 2002;33:1113-1119
9. Stagliano NE, Zhao W, Prado R, Dewanjee MK, Ginsberg MD, Dictrich WD. The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab 1997;17:1182-1190
10. Kidwell CS, Liebeskind DS, Starkman S, Saver JL. Trends in acute ischemic stroke trials through the 20th century. Stroke 2001;32:1349-1359
11. Faden AI. Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol 2002;15:707-712
12. Faden AI. Neuroprotection and traumatic brain injury: the search continues. Arch Neurol 2001;58:1553-1555
13. Gladstone DJ, Black SE, Hakim AM. Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions. Stroke 2002;33:2123-2136
14. Xiong L, Zheng Y, Wu M, et al. Preconditioning with isoflurane produces dosedependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats. Anesth Analg 2003;96:233-237
15. Kawaguchi M, Kimbro JR, Drummond JC, Cole DJ, Kelly PJ, Patel PM. Isoflurane delays but does not prevent cerebral infarction in rats subjected to focal ischemia. Anesthesiology 2000;92:1335-1342
16. Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999;30:2752-2758
17. Boast CA, Gerhardt SC, Pastor G, Lehmann J, Etienne PE, Liebman JM. The N-methyl-D-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils. Brain Res 1988;442:345-348
18. Perez-Pinzon MA, Maier CM, Yoon EJ, Sun GH, Giffard RG, Steinberg GK. Correlation of CGS 19755 neuroprotection against in vitro excitotoxicity and focal cerebral ischemia. J Cereb Blood Flow Metab 1995;15:865-876
19. Grotta J, Clark W, Coull B, et al. Safety and tolerability of the glutamate antagonist CGS 19755 (selfotel) in patients with acute ischemic stroke: results of a phase IIa randomized trial. Stroke 1995;26:602-605
20. Davis SM, Lees KR, Albers GW, et al. Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 2000;31:347-354
21. Dawson DA, Wadsworth G, Palmer AM. A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke. Brain Res 2001;892:344-350
22. Lees KR. Prospects for improved neuroprotection trials in stroke. In: Cerebrovascular Disease. United Kingdom: Cambridge University Press, 2002:430-433
23. Grotta JC. Acute stroke therapy at the millennium: consummating the marriage between the laboratory and bedside: the Feinberg lecture. Stroke 1999;30:1722-1728
24. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587
25. Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS 11): Second European-Australasian Acute Stroke Study Investigators. Lancet 1998;352:1245-1251
26. Astrup J, Siesjo BK, Symon L. Thresholds in cerebral ischemia: the ischemic penumbra. Stroke 1981;12:723-725
27. Takagi K, Ginsberg MD, Globus MY, et al. Changes in amino acid neurotransmitters and cerebral blood flow in the ischemic penumbral region following middle cerebral artery occlusion in the rat: correlation with histopathology. J Cereb Blood Flow Metab 1993;13:575-585
28. Sharp FR, Lu A, Tang Y, Millhorn DE. Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab 2000;20:1011-1032
29. Wang CX, Todd KG, Yang Y, Gordon T, Shuaib A. Patency of cerebral microvessels after focal embolic stroke in the rat. J Cereb Blood Flow Metab 2001;21:413-421
30. Dictrich WD, Prado R, Watson BD, Busto R, Ginsberg MD. Hemodynamic consequences of common carotid artery thrombosis and thrombogenically activated blood in rats. J Cereb Blood Flow Metab 1991;11:957-965
31. Dietrich WD, Danton G, Hopkins AC, Prado R. Thromboembolic events predispose the brain to widespread cerebral infarction after delayed transient global ischemia in rats. Stroke 1999;30:855-861; discussion 862
32. Schlaug G, Benfield A, Baird AE, et al. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 1999;53:1528-1537
33. Baron JC. Mapping the ischaemic penumbra with PET: a new approach. Brain 2001;124:2-4
34. Heiss WD. Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab 2000;20:1276-1293
35. Hakim AM, Evans AC, Berger L, et al. The effect of nimodipine on the evolution of human cerebral infarction studied by PET. J Cereb Blood Flow Metab 1989;9:523-534
36. Baron JC. Mapping the ischaemic penumbra with PET: implications for acute stroke treatment. Cerebrovasc Dis 1999;9:193-201
37. Heiss WD, Kracht LW, Thiel A, Grond M, Pawlik G. Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia. Brain 2001;124:20-29
38. Yao H, Markgraf CG, Dietrich WD, Prado R, Watson BD, Ginsberg MD. Glutamate antagonist MK-801 attenuates incomplete but not complete infarction in thrombotic distal middle cerebral artery occlusion in Wistar rats. Brain Res 1994;642:117-122
39. Lin B, Dietrich WD, Ginsberg MD, Globus MY, Busto R. MK-801 (dizocilpine) protects the brain from repeated normothermic global ischemic insults in the rat. J Cereb Blood Flow Metab 1993;13:925-932
40. Yam PS, Dunn LT, Graham DI, Dewar D, McCulloch J. NMDA receptor blockade fails to alter axonal injury in focal cerebral ischemia. J Cereb Blood Flow Metab 2000;20:772-779
41. McCracken E, Fowler JH, Dewar D, Morrison S, McCulloch J. Grey matter and white matter ischemic damage is reduced by the competitive AMPA receptor antagonist, SPD 502. J Cereb Blood Flow Metab 2002;22:1090-1097
42. Hurn PD, Macrae IM. Estrogen as a neuroprotectant in stroke. J Cereb Blood Flow Metab 2000;20:631-652
43. Li K, Futrell N, Tovar S, Wang LC, Wang DZ, Schultz LR. Gender influences the magnitude of the inflammatory response within embolic cerebral infarcts in young rats. Stroke 1996;27:498-503
44. Hall ED, Pazara KE, Linseman KL. Sex differences in postischemic neuronal necrosis in gerbils. J Cereb Blood Flow Metab 1991;11:292-298
45. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD. Gender-linked brain injury in experimental stroke. Stroke 1998;29:159-165; discussion 166
46. Bramlett HM, Dietrich WD. Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J Neurotrauma 2001;18:891-900
47. Hawk T, Zhang YQ, Rajakumar G, Day AL, Simpkins JW. Testosterone increases and estradiol decreases middle cerebral artery occlusion lesion size in male rats. Brain Res 1998;796:296-298
48. Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative - a randomized trial. JAMA 2003;289:2673-2684
49. Suzuki T, Bramlett H, Dietrich W. The importance of gender on the beneficial effects of posttraumatic hypothermia. Exp Neurol 2004; in press
50. Baird AE, Dambrosia J, Janket S, et al. A three-item scale for the early prediction of stroke recovery. Lancet 2001;357:2095-2099
51. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy: ASPECTS Study Group - Alberta Stroke Programme Early CT Score. Lancet 2000;355:1670-1674
52. Schaefer PW, Ozsunar Y, He J, et al. Assessing tissue viability with MR diffusion and perfusion imaging. AJNR Am J Neuroradiol 2003;24:436-443
53. Stagliano NE, Dietrich WD, Prado R, Green EJ, Busto R. The role of nitric oxide in the pathophysiology of thromboembolic stroke in the rat. Brain Res 1997;759:32-40
54. Markgraf CG, Green EJ, Hurwitz BE, et al. Sensorimotor and cognitive consequences of middle cerebral artery occlusion in rats. Brain Res 1992;575:238-246
55. Duncan PW, Jorgensen HS, Wade DT. Outcome measures in acute stroke trials: a systematic review and some recommendations to improve practice. Stroke 2000;31:1429-1438
56. Warach S. New imaging strategies for patient selection for thrombolytic and neuroprotective therapies. Neurology 2001;57:S48-52
57. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in mammalian central nervous system. J Cereb Blood Flow Metab 2003;23:513-530
58. Wassmann H, Greiner C, Hulsmann S, et al. Hypothermia as cerebroprotective measure: experimental hypoxic exposure of brain slices and clinical application in critically reduced cerebral perfusion pressure. Neurol Res 1998;20(suppl 1):S61-65
59. Taylor CP, Meldrum BS. Na+ channels as targets for neuroprotective drugs. Trends Pharmacol Sci 1995;16:309-316
60. Ovbiagele B, Kidwell CS, Starkman S, Saver JL. Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep 2003;3:9-20
61. Jain KK. Neuroprotection in cerebrovascular disease. Expert Opin Investig Drugs 2000;9:695-711
62. Nakayama H, Dietrich WD, Watson BD, Busto R, Ginsberg MD. Photothrombotic occlusion of rat middle cerebral artery: histopathological and hemodynamic sequelae of acute recanalization. J Cereb Blood Flow Metab 1988;8:357-366
63. Clark WM, Lutsep HL. Medical treatment strategies: intravenous thrombolysis, neuronal protection, and anti-reperfusion injury agents. Neuroimaging Clin N Am 1999;9:465-473
64. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255-266
65. Rataud J, Debarnot F, Mary V, Pratt J, Stutzmann JM. Comparative study of voltage-sensitive sodium channel blockers in focal ischaemia and electric convulsions in rodents. Neurosci Lett 1994;172:19-23
66. Taft WC, Clifton GL, Blair RE, DeLorenzo RJ. Phenytoin protects against ischemia-produced neuronal cell death. Brain Res 1989;483:143-148
67. Pratt J, Rataud J, Bardot F, et al. Neuroprotective actions of riluzole in rodent models of global and focal cerebral ischaemia. Neurosci Lett 1992;140:225-230
68. Smith SE, Hodges H, Sowinski P, et al. Long-term beneficial effects of BW619C89 on neurological deficit, cognitive deficit and brain damage after middle cerebral artery occlusion in the rat. Neuroscience 1997;77:1123-1135
69. Gribkoff VK, Starrett JE Jr, Dworetzky SI, et al. Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels. Nat Med 2001;7:471-477
70. Muir KW, Holzapfel L, Lees KR. Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis 2000;10:431-436
71. Jensen BS. BMS-204352: a potassium channel opener developed for the treatment of stroke. CNS Drug Rev 2002;8:353-360
72. Mackay KB. BMS-204352 (Bristol Myers Squibb). Curr Opin Investig Drugs 2001;2:820-823
73. Horn J, Limburg M. Calcium antagonists for ischemic stroke: a systematic review. Stroke 2001;32:570-576
74. Lin BW, Dietrich WD, Busto R, Ginsberg MD. (S)-emopamil protects against global ischemic brain injury in rats. Stroke 1990;21:1734-1739
75. Nakayama H, Ginsberg MD, Dietrich WD. (S)-emopamil, a novel calcium channel blocker and serotonin S2 antagonist, markedly reduces infarct size following middle cerebral artery occlusion in the rat. Neurology 1988;38:1667-1673
76. Bielenberg GW, Beck T. The effects of dizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat. Brain Res 1991;552:338-342
77. Vibulsresth S, Dietrich WD, Busto R, Ginsberg MD. Failure of nimodipine to prevent ischemic neuronal damage in rats. Stroke 1987;18:210-216
78. Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer HJ. A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med 1988;318:203-207
79. Sze KH, Sim TC, Wong E, Cheng S, Woo J. Effect of nimodipine on memory after cerebral infarction. Acta Neurol Scand 1998;97:386-392
80. Gelmers HJ. The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurol Scand 1984;69:232-239
81. Martinez-Vila E, Guillen F, Villanueva JA, et al. Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction. Stroke 1990;21:1023-1028
82. Franke CL, Palm R, Dalby M, et al. Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands. Acta Neurol Scand 1996;93:56-60
83. Limburg M, Hijdra A. Flunarizine in acute ischemic stroke: a pilot study. Eur Neurol 1990;30:121-122
84. Frandsen A, Schousboe A. Dantrolene prevents glutamate cytotoxicity and Ca2+ release from intracellular stores in cultured cerebral cortical neurons. J Neurochem 1991;56:1075-1078
85. Hong SJ, Chiou GC. Effects of intracellular calcium reduction by dantrolene on prevention/treatment of ischemic stroke. J Cardiovasc Pharmacol Ther 1998;3:299-304
86. Zhang L, Andou Y, Masuda S, Mitani A, Kataoka K. Dantrolene protects against ischemic, delayed neuronal death in gerbil brain. Neurosci Lett 1993;158:105-108
87. Kross J, Fleischer JE, Milde JH, Gronert GA. No dantrolene protection in a dog model of complete cerebral ischaemia. Neurol Res 1993;15:37-40
88. Nakamura K, Hatakeyama T, Furuta S, Sakaki S. The role of early Ca2+ influx in the pathogenesis of delayed neuronal death after brief forebrain ischemia in gerbils. Brain Res 1993;613:181-192
89. Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 1997;49:S66-69
90. Buchan AM, Slivka A, Xue D. The effect of the NMDA receptor antagonist MK-801 on cerebral blood flow and infarct volume in experimental focal stroke. Brain Res 1992;574:171-177
91. Dirnagl U, Tanabe J, Polsinelli W. Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat. Brain Res 1990;527:62-68
92. Suzuki Y, Takagi Y, Nakamura R, Hashimoto K, Umemura K. Ability of NMDA and non-NMDA receptor antagonists to inhibit cerebral ischemic damage in aged rats. Brain Res 2003;964:116-120
93. Green EJ, Pazos AJ, Dietrich WD, et al. Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats. Brain Res 1995;702:145-152
94. Yao H, Ginsberg MD, Watson BD, et al. Failure of MK-801 to reduce infarct volume in thrombotic middle cerebral artery occlusion in rats. Stroke 1993;24:864-870; discussion 870-871
95. Auer RN, Coupland SG, Jason GW, et al. Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia. Mol Chem Neuropathol 1996;29:193-210
96. Kermer P, Klocker N, Bahr M. Neuronal death after brain injury: models, mechanisms, and therapeutic strategies in vivo. Cell Tissue Res 1999;298:383-395
97. Pitsikas N, Brambilla A, Besozzi C, et al. Effects of cerestat and NBQX on functional and morphological outcomes in rat focal cerebral ischemia. Pharmacol Biochem Behav 2001;68:443-447
98. Dyker AG, Edwards KR, Fayad PB, Hormes JT, Lees KR. Safety and tolerability study of aptiganel hydrochloride in patients with an acute ischemic stroke. Stroke 1999;30:2038-2042
99. Yang Y, Li Q, Yang T, Hussain M, Shuaib A. Reduced brain infarct volume and improved nenrological ontcome by inhibition of the NR2B subunit of NMDA receptors by using CP101, 606-27 alone and in combination with rt-PA in a thromboembolic stroke model in rats. J Neurosurg 2003;98:397-403
100. Di X, Bullock R, Watson J, et al. Effect of CP101, 606, a novel NR2B subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage off cytotoxic brain edema after middle cerebral artery occlusion in the feline brain. Stroke 1997;28:2244-2251
101. Bullock MR, Merchant RE, Carmack CA, et al. An open-label study of CP-101, 606 in subjects with a severe traumatic head injury or spontaneous intracerebral hemorrhage. Ann N Y Acad Sci 1999;890:51-58
102. Davis SM, Albers GW, Diener HC, Lees KR, Norris J. Termination of Acute Stroke Studies Involving Selfotel Treatment: ASSIST Steering Committed (abstract). Lancet 1997;349:32
103. Mueller AL, Artman LD, Balandrin MF, et al. NPS 1506, a novel NMDA receptor antagonist and neuroprotectant: review of preclinical and clinical studies. Ann N Y Acad Sci 1999;890:450-457
104. Takahashi M, Ni JW, Kawasaki-Yatsugi S, et al. Neuroprotective efficacy of YM872, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, after permanent middle cerebral artery occlusion in rats. J Pharmacol Exp Ther 1998;287:559-566
105. Kawasaki-Yatsugi S, Ichiki C, Yatsugi S, et al. Neuroprotective effects of an AMPA receptor antagonist YM872 in a rat transient middle cerebral artery occlusion model. Neuropharmacology 2000;39:211-217
106. Suzuki M, Sasamata M, Miyata K. Neuroprotective effects of YM872 coadministered with t-PA in a rat embolic stroke model. Brain Res 2003;959:169-172
107. Williams AJ, Lu XM, Slusher B, Tortella FC. Electroencephalogram analysis and neuroprotective profile of the N-acetylated-alpha-linked acidic dipeptidase inhibitor, GPI5232, in normal and brain-injured rats. J Pharmacol Exp Ther 2001;299:48-57
108. Tortella FC, Lin Y, Ved H, Slusher BS, Dave JR. Neuroprotection produced by the NAALADase inhibitor 2-PMPA in rat cerebellar neurons. Eur J Pharmacol 2000;402:31-37
109. Vornov JJ, Wozniak K, Lu M, et al. Blockade of NAALADase: a novel neuroprotective strategy based on limiting glutamate and elevating NAAG. Ann N Y Acad Sci 1999;890:400-405
110. Slusher BS, Vornov JJ, Thomas AG, et al. Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury. Nat Med 1999;5:1396-1402
111. Flor PJ, Battaglia G, Nicoletti F, Gasparini F, Bruno V. Neuroprotective activity of metabotropic glutamate receptor ligands. Adv Exp Med Biol 2002;513:197-223
112. De Vry J, Horvath E, Schreiber R. Neuroprotective and behavioral effects of the selective metabotropic glutamate mGlu(1) receptor antagonist BAY 36-7620. Eur J Pharmacol 2001;428:203-214
113. Muir KW. Magnesium in stroke treatment. Postgrad Med J 2002;78:641-645
114. Schwartz-Bloom RD, Sah R. ā-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 2001;77:353-371
115. Lyden P, Shuaib A, Ng K, et al. Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results. Stroke 2002;33:122-128
116. Danton G, Watson BD, Prado R, Dietric WD. Endothelium-targeted pharmacotherapeutics for the treatment of stroke. Curr Opin Investig Drugs 2002;3:896-904
117. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271:C1424-1437
118. Kontos HA. Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke 2001;32:2712-2716
119. Hall ED, Andrus PK, Smith SL, et al. Neuroprotective efficacy of microvascularly-localized versus brain-penetrating antioxidants. Acta Neurochir Suppl (Wien) 1996;66:107-113
120. Cao X, Phillis JW. á-Phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia. Brain Res 1994;644:267-272
121. Marshall JW, Duffin KJ, Green AR, Ridley RM. NXY-059, a free radical-trapping agent, substantially lessens the functional disability resulting from cerebral ischemia in a primate species. Stroke 2001;32:190-198
122. Tirilazad International Steering Committee. Tirilazad mesylate in acute ischemic stroke: a systematic review. Stroke 2000;31:2257-2265
123. Di Mascio R, Marchioli R, Tognoni G. Cholesterol reduction and stroke occurrence: an overview of randomized clinical trials. Cerebrovasc Dis 2000;10:85-92
124. Blauw GJ, Lagaay AM, Smelt AH, Westendorp RG. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 1997;28:946-950
125. Gorelick PB, Sacco RL, Smith DB, et al. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. JAMA 1999;281:1112-1120
126. Szucs TD. Pharmaco-economic aspects of lipid-lowering therapy: is it worth the price? Eur Heart J 1998;19(suppl M):M22-28
127. Vaughan CJ, Delanty N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 1999;30:1969-1973
128. Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 2001;32:980-986
129. Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol 2003;62:127-136
130. Zhang R, Chopp M, Zhang Z, Jiang N, Powers C. The expression of P- and E-selectins in three models of middle cerebral artery occlusion. Brain Res 1998;785:207-214
131. Okada Y, Copeland BR, Mori E, Tung MM, Thomas WS, del Zoppo GJ. P-selectin and intercellular adhesion molecule-1 expression after focal brain ischemia and reperfusion. Stroke 1994;25:202-211
132. Goussev AV, Zhang Z, Anderson DC, Chopp M. P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat. J Neurol Sci 1998;161:16-22
133. Connolly ES Jr, Winfree CJ, Prestigiacomo CJ, et al. Exacerbation of cerebral injury in mice that express the P-selectin gene: identification of P-selectin blockade as a new target for the treatment of stroke. Circ Res 1997;81:304-310
134. Zhang RL, Chopp M, Jiang N, et al. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 1995;26:1438-1442; discussion 1443
135. Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology 2001;57:1428-1434
136. Furuya K, Takeda H, Azhar S, et al. Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine antihuman intercellular adhesion molecule-1 antibody: a bedside-to-bench study. Stroke 2001;32:2665-2674
137. Jiang X, Namura S, Nagata I. Matrix metalloproteinase inhibitor KB-R7785 attenuates brain damage resulting from permanent focal cerebral ischemia in mice. Neurosci Lett 2001;305:41-44
138. Rosenberg GA, Estrada EY, Dencoff JE. Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 1998;29:2189-2195
139. Lapchak PA, Chapman DF, Zivin JA. Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke. Stroke 2000;31:3034-3040
140. Sumii T, Lo EH. Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 2002;33:831-836
141. Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 2001;93:178-193
142. Busto R, Dietrich WD, Globus MY, Valdes I, Scheinberg P, Ginsberg MD. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 1987;7:729-738
143. Green EJ, Dietrich WD, van Dijk F, et al. Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats. Brain Res 1992;580:197-204
144. Leonov Y, Sterz F, Safar P, et al. Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab 1990;10:57-70
145. Chen H, Chopp M, Zhang ZG, Garcia JH. The effect of hypothermia on transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1992;12:621-628
146. Barone FC, Feuerstein GZ, White RF. Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 1997;21:31-44
147. Onesti ST, Baker CJ, Sun PP, Solomon RA. Transient hypothermia reduces focal ischemic brain injury in the rat. Neurosurgery 1991;29:369-373
148. Zhang ZG, Chopp M, Chen H. Duration dependent post-ischemic hypothermia alleviates cortical damage after transient middle cerebral artery occlusion in the rat. J Neurol Sci 1993;117:240-244
149. Coimbra C, Wieloch T. Moderate hypothermia mitigates neuronal damage in the rat brain when initiated several hours following transient cerebral ischemia. Acta Neuropathol (Berl) 1994;87:325-331
150. Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556-563
151. Kammersgaard LP, Rasmussen BH, Jorgensen HS, Reith J, Weber U, Olsen TS. Feasibility and safety of inducing modest hypothermia in awake patients with acute stroke through surface cooling: a case-control study - the Copenhagen Stroke Study. Stroke 2000;31:2251-2256
152. Marion DW, White MJ. Treatment of experimental brain injury with moderate hypothermia and 21-aminosteroids. J Neurotrauma 1996;13:139-147
153. Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29:2461-2466
154. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-563
155. Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest (Published erratum appears in N Engl J Med 2002;346:1756.). N Engl J Med 2002;346:549-556
156. Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest (Published erratum appears in N Engl J Med 2002;346:1756.). N Engl J Med 2002;346:549-556
157. Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA. Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 2001;32:2033-2035
158. Steiner T, Friede T, Aschoff A, Schellinger PD, Schwab S, Hacke W. Effect and feasibility of controlled rewarming after moderate hypothermia in stroke patients with malignant infarction of the middle cerebral artery. Stroke 2001;32:2833-2835
159. Berger C, Schabitz WR, Georgiadis D, Steiner T, Aschoff A, Schwab S. Effects of hypothermia on excitatory amino acids and metabolism in stroke patients: a microdialysis study. Stroke 2002;33:519-524
160. Georgiadis D, Schwarz S, Kollmar R, Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 2001;32:2550-2553
161. Dietrich WD. Temperature changes and ischemic stroke. In: Fisher M, Bogousslavsky J, eds. Current Review of Cerebrovascular Disease. Philadelphia, Pa: Current Medicine, Inc.; 2001:45-55