Improving outcome after stroke: Overcoming the translational roadblock

被引:205
作者
Endres, Matthias [1 ]
Engelhardt, Britta [4 ]
Koistinaho, Jari [7 ]
Lindvall, Olle [8 ]
Meairs, Stephen [2 ]
Mohr, Jay P. [10 ]
Planas, Anna [11 ]
Rothwell, Nancy [12 ]
Schwaninger, Markus [3 ]
Schwab, Martin E. [5 ,6 ]
Vivien, Denis [13 ]
Wieloch, Tadeusz [9 ]
Dirnagl, Ulrich
机构
[1] Charite Univ Med Berlin, Ctr Stroke Res, Dept Neurol, Berlin, Germany
[2] Univ Heidelberg, Klinikum Mannheim, Dept Neurol, D-6800 Mannheim, Germany
[3] Humboldt Univ, Dept Neurol, DE-10098 Berlin, Germany
[4] Univ Bern, Theodor Kocher Inst, Bern, Switzerland
[5] Univ Zurich, Brain Res Inst, Zurich, Switzerland
[6] Swiss Fed Inst Technol, Dept Biol, Zurich, Switzerland
[7] Univ Kuopio, Dept Neurobiol, FIN-70211 Kuopio, Finland
[8] Lund Univ, Wallenberg Neurosci Ctr, Sect Restorat Neurol, Lund, Sweden
[9] Univ Sjukhuset, Wallenberg Neuroctr, Dept Clin Sci, Lund, Sweden
[10] Columbia Univ Coll Phys & Surg, Neurol Inst, New York, NY 10032 USA
[11] IDIBAPS, IIBB CSIC, Dept Brain Ischemia & Neurodegenerat, Barcelona, Spain
[12] Univ Manchester, Fac Life Sci, Manchester, Lancs, England
[13] GIP Cyceron, CNRS, UMR 6232,INSERM, CINAPS,U919,Serine Proteases & Pathophysiol Neuro, Caen, France
基金
英国医学研究理事会;
关键词
neuroprotection; brain ischaemia; stroke treatment;
D O I
10.1159/000118039
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Stroke poses a massive burden of disease, yet we have few effective therapies. The paucity of therapeutic options stands contrary to intensive research efforts. The failure of these past investments demands a thorough re-examination of the pathophysiology of ischaemic brain injury. Several critical areas hold the key to overcoming the translational roadblock: (1) vascular occlusion: current recanalization strategies have limited effectiveness and may have serious side effects; (2) complexity of stroke pathobiology: therapy must acknowledge the 'Janus-faced' nature of many stroke targets and must identify endogenous neuroprotective and repair mechanisms; repair; stroke outcome is modulated by the interaction of the injured brain with the immune system; (4) regeneration: the potential of the brain for reorganization, plasticity and repair after injury is much greater than previously thought; (5) confounding factors, long-term outcome and predictive modelling. These 5 areas are linked on all levels and therefore need to be tackled by an integrative approach and innovative therapeutic strategies. Copyright (c) 2008 S. Karger AG, Basel.
引用
收藏
页码:268 / 278
页数:11
相关论文
共 70 条
  • [1] Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis
    Agrawal, S
    Anderson, P
    Durbeej, M
    van Rooijen, N
    Ivars, F
    Opdenakker, G
    Sorokin, LM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (04) : 1007 - 1019
  • [2] Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke
    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
    Al-Senani, F
    Burgin, S
    Calleja, S
    Campbell, M
    Chen, CI
    Chernyshev, O
    Choi, J
    El-Mitwalli, A
    Felberg, R
    Ford, S
    Garami, Z
    Irr, W
    Grotta, J
    Hall, C
    Iguchi, Y
    Ireland, J
    Labiche, L
    Malkoff, M
    Morgenstern, L
    Noser, E
    Okon, N
    Piriyawat, P
    Robinson, D
    Shaltoni, H
    Shaw, S
    Uchino, K
    Yatsu, F
    Alvarez-Sabín, J
    Arenillas, JF
    Huertas, R
    Molina, C
    Montaner, J
    Ribó, M
    Rubiera, M
    Santamarina, E
    Saqqur, M
    Alchtar, N
    O'Rourke, F
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (21) : 2170 - 2178
  • [3] Interleukin-1 and neuronal injury
    Allan, SM
    Tyrrell, PJ
    Rothwell, NJ
    [J]. NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) : 629 - 640
  • [4] Neuronal replacement from endogenous precursors in the adult brain after stroke
    Arvidsson, A
    Collin, T
    Kirik, D
    Kokaia, Z
    Lindvall, O
    [J]. NATURE MEDICINE, 2002, 8 (09) : 963 - 970
  • [5] Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization
    Asahara, T
    Masuda, H
    Takahashi, T
    Kalka, C
    Pastore, C
    Silver, M
    Kearne, M
    Magner, M
    Isner, JM
    [J]. CIRCULATION RESEARCH, 1999, 85 (03) : 221 - 228
  • [6] CORTICAL EVOKED-POTENTIAL AND EXTRACELLULAR K+ AND H+ AT CRITICAL LEVELS OF BRAIN ISCHEMIA
    ASTRUP, J
    SYMON, L
    BRANSTON, NM
    LASSEN, NA
    [J]. STROKE, 1977, 8 (01) : 51 - 57
  • [7] Equivocal roles of tissue-type plasminogen activator in stroke-induced injury
    Benchenane, K
    López-Atalaya, JP
    Fernández-Monreal, M
    Touzani, O
    Vivien, D
    [J]. TRENDS IN NEUROSCIENCES, 2004, 27 (03) : 155 - 160
  • [8] NMDA and AMPA/kainate glutamate receptors modulate dentate neurogenesis and CA3 synapsin-I in normal and ischemic hippocampus
    Bernabeu, R
    Sharp, FR
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (12) : 1669 - 1680
  • [9] The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury
    Conner, JM
    Chiba, AA
    Tuszynski, MH
    [J]. NEURON, 2005, 46 (02) : 173 - 179
  • [10] Ischemic tolerance and endogenous neuroprotection
    Dirnagl, U
    Simon, RP
    Hallenbeck, JM
    [J]. TRENDS IN NEUROSCIENCES, 2003, 26 (05) : 248 - 254