Katsuki Hiroshi, Hijioka Masanori
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University.
Biol Pharm Bull. 2017;40(5):564-568. doi: 10.1248/bpb.b16-01013.
Intracerebral hemorrhage (ICH) is a neurological disorder frequently accompanied by severe dysfunction. Critical pathogenic events leading to poor prognosis should be identified for the development of novel effective therapies for ICH. Here we focus on the injury of the axonal tract, particularly of the internal capsule, with reference to its contribution to ICH pathology and potential therapeutic interventions in addition to its cellular mechanisms. Studies on human ICH patients and rodent models of ICH suggest that invasion of hematoma into the internal capsule greatly worsens the severity of post-ICH symptoms. A blood-derived protease thrombin may play an important role in the acute phase of axonal tract injury in the internal capsule that includes compromised axonal transport and fragmentation of axonal structures. Several agents such as clioquinol, melatonin and Am80 (a retinoic acid receptor agonist) have been shown to produce therapeutic effects on rodent models of ICH associated with injury of the internal capsule. In the course of examinations on the effect of Am80, we obtained evidence for the involvement of CXCL2, a neutrophil chemotactic factor, in the pathogenesis of ICH. Accordingly, we also refer to the potential roles of infiltrating neutrophils and inflammatory responses in axonal tract injury and resultant neurological dysfunction in ICH.
脑出血（ICH）是一种常伴有严重功能障碍的神经系统疾病。为了开发针对脑出血的新型有效疗法，应确定导致预后不良的关键致病事件。在此，我们聚焦于轴突束损伤，尤其是内囊的损伤，探讨其对脑出血病理的影响、潜在治疗干预措施及其细胞机制。对脑出血患者和啮齿动物脑出血模型的研究表明，血肿侵入内囊会极大地加重脑出血后症状的严重程度。血液来源的蛋白酶凝血酶可能在内囊轴突束损伤的急性期起重要作用，这包括轴突运输受损和轴突结构碎片化。几种药物，如氯碘羟喹、褪黑素和Am80（一种视黄酸受体激动剂），已被证明对与内囊损伤相关的啮齿动物脑出血模型具有治疗作用。在研究Am80的作用过程中，我们获得了证据，表明中性粒细胞趋化因子CXCL2参与了脑出血的发病机制。因此，我们还探讨了浸润性中性粒细胞和炎症反应在脑出血轴突束损伤及由此导致的神经功能障碍中的潜在作用。
