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
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