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Updated: May 31, 2026
Autologous Blood Injection to Model Spontaneous Intracerebral Hemorrhage in Mice
Published on: August 24, 2011
Geldanamycin reduced brain injury in mouse model of intracerebral hemorrhage
Anatol Manaenko1, Nancy Fathali, Shammah Williams
1Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
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.
Insights
Geldanamycin, a heat shock protein inducer, reduced brain swelling and improved neurological function in mice after intracerebral hemorrhage (ICH). This suggests geldanamycin offers neuroprotection and is a potential therapeutic target for ICH.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Intracerebral hemorrhage (ICH) causes secondary brain injury.
- Heat shock proteins (HSPs) play a role in cellular protection.
- Geldanamycin is an inducer of HSPs.
Purpose of the Study:
- To investigate the neuroprotective effects of geldanamycin in a mouse model of ICH.
- To evaluate the impact of geldanamycin on brain edema and neurological deficits post-ICH.
Main Methods:
- Mice with ICH were treated with vehicle or geldanamycin (1 or 10 mg/kg).
- Neurological deficits were assessed using Garcia neuroscoring, wire hanging, and beam balance tests.
- Brain water content was measured using the wet/dry weight method at 24 and 72 hours post-ICH.
Main Results:
- Geldanamycin (10 mg/kg) significantly reduced ICH-induced brain water content at both 24 and 72 hours.
- Geldanamycin administration improved neurological outcomes in Garcia and beam balance tests at 72 hours.
- HSP induction by geldanamycin correlated with neuroprotection.
Conclusions:
- Geldanamycin demonstrates significant neuroprotective effects in an ICH mouse model.
- Reducing brain edema and improving neurological function are key benefits observed.
- Targeting HSP induction with geldanamycin represents a promising therapeutic strategy for ICH.
