Exploring Neuroprotective Drug Therapies for Intracerebral Hemorrhage

被引:56
作者
Katsuki, Hiroshi [1 ]
机构
[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Chemicopharmacol Sci, Kumamoto 8620973, Japan
基金
日本学术振兴会;
关键词
hemorrhagic stroke; matrix metalloproteinase; heme; peroxisome proliferator-activated receptor; retinoid; BLOOD-BRAIN-BARRIER; ACTIVATED-RECEPTOR-GAMMA; PROTEIN-KINASE PATHWAYS; PRIOR STATIN USE; RAT MODEL; MATRIX METALLOPROTEINASES; HEME OXYGENASE; DEXAMETHASONE TREATMENT; SENSORIMOTOR RECOVERY; REDUCES APOPTOSIS;
D O I
10.1254/jphs.10R05CR
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high mortality and poor prognosis, for which virtually no effective drug therapies are available at present Experimental animal models, based on intrastriatal injection of collagenase or autologous blood, have enabled great advances in elucidation of cellular/molecular events contributing to brain pathogenesis associated with ICH Many lines of evidence indicate that blood constituents, including hemoglobin-derived products as well as proteases such as thrombin, play important roles in the pathogenic events Inflammatory reactions involving neutrophils, activated microglia, and production of proinflammatory cytokines also constitute a critical aspect of pathology leading to neurodegeneration and tissue damage Efforts are continuing to find drugs that potentially alleviate pathological and neurological outcomes of ICH Various drugs that possess antioxidative, anti-inflammatory or neurotrophic/neuroprotective properties have been demonstrated to produce therapeutic effects on ICH animal models Drugs already in clinical use such as minocycline, statins, and several nuclear receptor ligands are among the list of effective drugs, but whether they also show therapeutic efficacy in human ICH patients remains unproven Here, current knowledge of ICH pathogenesis and problems arising with respect to exploration of new drug candidates are discussed
引用
收藏
页码:366 / 378
页数:13
相关论文
共 100 条
  • [1] Temporal profile of matrix metalloproteinases and their inhibitors after spontaneous intracerebral hemorrhage -: Relationship to clinical and radiological outcome
    Alvarez-Sabín, J
    Delgado, P
    Abilleira, S
    Molina, CA
    Arenillas, J
    Ribó, M
    Santamarina, E
    Quintana, M
    Monasterio, J
    Montaner, J
    [J]. STROKE, 2004, 35 (06) : 1316 - 1322
  • [2] Src kinase inhibition improves acute outcomes after experimental intracerebral hemorrhage
    Ardizzone, Timothy D.
    Zhan, Xinhua
    Ander, Brad P.
    Sharp, Frank R.
    [J]. STROKE, 2007, 38 (05) : 1621 - 1625
  • [3] Genomic profiles of damage and protection in human intracerebral hemorrhage
    Carmichael, S. Thomas
    Vespa, Paul M.
    Saver, Jeffery L.
    Coppola, Giovanni
    Geschwind, Daniel H.
    Starkman, Sidney
    Miller, Chad M.
    Kidwell, Chelsea S.
    Liebeskind, David S.
    Martin, Neil A.
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2008, 28 (11) : 1860 - 1875
  • [4] Peroxisome proliferator-activated receptor agonist regulation of glial activation: Relevance to CNS inflammatory disorders
    Drew, Paul D.
    Xu, Jihong
    Storer, Paul D.
    Chavis, Janet A.
    Racke, Michael K.
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2006, 49 (02) : 183 - 189
  • [5] The complement cascade as a therapeutic target in intracerebral hemorrhage
    Ducruet, Andrew F.
    Zacharia, Brad E.
    Hickman, Zachary L.
    Grobelny, Bartosz T.
    Yeh, Mason L.
    Sosunov, Sergey A.
    Connolly, E. Sander, Jr.
    [J]. EXPERIMENTAL NEUROLOGY, 2009, 219 (02) : 398 - 403
  • [6] Effect of statins on intracerebral hemorrhage outcome and recurrence
    FitzMaurice, Emilie
    Wendell, Lauren
    Snider, Ryan
    Schwab, Kristin
    Chanderraj, Rishi
    Kinnecom, Cathrine
    Nandigam, Kaveer
    Rost, Natalia S.
    Viswanathan, Anand
    Rosand, Jonathan
    Greenberg, Steven M.
    Smith, Eric E.
    [J]. STROKE, 2008, 39 (07) : 2151 - 2154
  • [7] Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo
    Fujimoto, S.
    Katsuki, H.
    Ohnishi, M.
    Takagi, M.
    Kume, T.
    Akaike, A.
    [J]. NEUROSCIENCE, 2007, 144 (02) : 694 - 701
  • [8] Thrombin-induced delayed injury involves multiple and distinct signaling pathways in the cerebral cortex and the striatum in organotypic slice cultures
    Fujimoto, S
    Katsuki, H
    Kume, T
    Akaike, A
    [J]. NEUROBIOLOGY OF DISEASE, 2006, 22 (01) : 130 - 142
  • [9] Plasminogen potentiates thrombin cytotoxicity and contributes to pathology of intracerebral hemorrhage in rats
    Fujimoto, Shinji
    Katsuki, Hiroshi
    Ohnishi, Masatoshi
    Takagi, Mikako
    Kume, Toshiaki
    Akaike, Akinori
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2008, 28 (03) : 506 - 515
  • [10] Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage
    Garrett, Matthew C.
    Otten, Marc L.
    Starke, Robert M.
    Komotar, Ricardo J.
    Magotti, Paola
    Lambris, John D.
    Rynkowski, Michal A.
    Connolly, E. Sander
    [J]. BRAIN RESEARCH, 2009, 1298 : 171 - 177