title: Geldanamycin reduced brain injury in mouse model of intracerebral hemorrhage.
abstract: 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.
authors: Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
authors: Anatol
authors: A
authors: Manaenko
authors: Nancy
authors: N
authors: Fathali
authors: Shammah
authors: S
authors: Williams
authors: Tim
authors: T
authors: Lekic
authors: John H
authors: JH
authors: Zhang
authors: Jiping
authors: J
authors: Tang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D002543:Cerebral Hemorrhage / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007839:Functional Laterality; D047029:Lactams, Macrocyclic / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors
chemical_list: D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; C001277:geldanamycin