title: Exploring neuroprotective drug therapies for intracerebral hemorrhage.
abstract: 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.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan. hkatsuki@gpo.kumamoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D016207:Cytokines / Q000502:physiology; D015195:Drug Design; D016166:Free Radical Scavengers; D005971:Glutamates / Q000502:physiology; D006418:Heme / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D020782:Matrix Metalloproteinases / Q000502:physiology; D008911:Minocycline; D018696:Neuroprotective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D013917:Thrombin / Q000502:physiology
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D005971:Glutamates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D018696:Neuroprotective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D006418:Heme; D013917:Thrombin; D020782:Matrix Metalloproteinases; D008911:Minocycline