Manaenko Anatol, Fathali Nancy, Williams Shammah, Lekic Tim, Zhang John H, Tang Jiping
Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
Acta Neurochir Suppl. 2011;111:161-5. doi: 10.1007/978-3-7091-0693-8_27.
We investigated the effect of the heat shock protein inducer geldanamycin on the development of secondary brain injury after ICH in mice. The effect of the drug at two different concentrations was evaluated at two time points: 24 and 72 h after ICH induction. In the first part of this study, a total of 30 male CD-1 mice were randomly divided into four groups: one sham group and three ICH groups. ICH animals received either an intraperitoneal injection of vehicle or geldanamycin (1 or 10 mg/kg). Neurological deficits and brain water content were evaluated 24 h after ICH. In the second part of this study, the effect of a high concentration of geldanamycin was evaluated 72 h after ICH. Neurological deficits were evaluated by the Garcia neuroscoring, wire hanging and beam balance tests. For estimation of brain water content, the "wet/dry weight" method was used. We demonstrated that administration of geldanamycin (10 mg/kg) ameliorated ICH-induced increase of brain water content significantly in both parts of the study. Geldanamycin improved the neurological outcome according to performance on Garcia and beam balance tests in the 72 h part of this study. Geldanamycin-induced induction of heat shock protein after ICH has a neuroprotective effect and may be a therapeutic target for ICH.
我们研究了热休克蛋白诱导剂格尔德霉素对小鼠脑出血后继发性脑损伤发展的影响。在脑出血诱导后的两个时间点(24小时和72小时)评估了该药物在两种不同浓度下的作用。在本研究的第一部分,总共30只雄性CD-1小鼠被随机分为四组:一组假手术组和三组脑出血组。脑出血动物接受腹腔注射溶剂或格尔德霉素(1或10毫克/千克)。在脑出血后24小时评估神经功能缺损和脑含水量。在本研究的第二部分,在脑出血后72小时评估高浓度格尔德霉素的作用。通过加西亚神经评分、悬线和横梁平衡试验评估神经功能缺损。为了估计脑含水量,采用了“湿/干重”法。我们证明,在本研究的两个部分中,给予格尔德霉素(10毫克/千克)均能显著改善脑出血诱导的脑含水量增加。根据本研究72小时部分的加西亚和横梁平衡试验结果,格尔德霉素改善了神经功能结局。脑出血后格尔德霉素诱导的热休克蛋白具有神经保护作用,可能是脑出血的一个治疗靶点。