TY - CHAP
T1 - Geldanamycin reduced brain injury in mouse model of intracerebral hemorrhage
AU - Manaenko, Anatol
AU - Fathali, Nancy
AU - Williams, Shammah
AU - Lekic, Tim
AU - Zhang, John H.
AU - Tang, Jiping
N1 - Funding Information:
Acknowledgement This study is partially supported by NIH NS053407 to J.H. Zhang and NS060936 to J. Tang. Conflict of interest statement
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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. © 2011 Springer-Verlag/Wien.
AB - 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. © 2011 Springer-Verlag/Wien.
KW - Geldanamycin
KW - HSP
KW - ICH
KW - Neuroprotection
KW - Male
KW - Brain Edema/drug therapy
KW - Functional Laterality
KW - Cerebral Hemorrhage/complications
KW - Brain/drug effects
KW - Dose-Response Relationship, Drug
KW - Nervous System Diseases/drug therapy
KW - Animals
KW - Brain Injuries/drug therapy
KW - Analysis of Variance
KW - Time Factors
KW - Enzyme Inhibitors/therapeutic use
KW - Lactams, Macrocyclic/therapeutic use
KW - Benzoquinones/therapeutic use
KW - Mice
KW - Disease Models, Animal
UR - https://www.scopus.com/pages/publications/79960692574
UR - https://www.scopus.com/pages/publications/79960692574#tab=citedBy
UR - https://www.mendeley.com/catalogue/7b38037c-c83f-3d6f-bc40-adac9c81515f/
U2 - 10.1007/978-3-7091-0693-8_27
DO - 10.1007/978-3-7091-0693-8_27
M3 - Chapter
C2 - 21725749
SN - 9783709106921
SN - 978-3-7091-2007-1
T3 - Acta Neurochirurgica, Supplementum
SP - 161
EP - 165
BT - Intracerebral Hemorrhage Research
PB - Springer Vienna
ER -