Abstract
This study investigated the effect of geldanamycin post-treatment on the development of secondary brain injury and neurological deficits in a mouse model of intracerebral hemorrhage. CD-1 mice received stereotactic injection of collagenase type VII into the right basal ganglia. Treatment groups were administered 1 mg/kg (low dose) or 10 mg/kg (high dose) of geldanamycin. Mice were euthanized at two time-points: 24 h or 72 h Blood-brain-barrier permeability, brain edema, and neurobehavioral deficits were assessed. Additionally, the effects of geldanamycin on heat shock protein 27 and 72; tumor necrosis factor-alpha and interleukin 1 beta expressions were evaluated.High dose geldanamycin significantly attenuated blood-brain barrier disruption and brain edema after intracerebral hemorrhage. Neurobehavioral outcomes were significantly improved in some parameters by high dose treatment. Molecular results showed a marked increase in heat shock protein 72 expression in ipsilateral brain of geldanamycin treated groups with a reduction in the pro-inflammatory tumor necrosis factor-alpha. Conclusion: Geldanamycin post-treatment is neuroprotective in the mouse model of intracerebral hemorrhage. Geldanamycin administration results in reduction of inflammation, preservation of blood-brain-barrier and amelioration of neurobehavioral deficits after an insult possibly by upregulation of heat shock protein 72. © 2010 Elsevier Ltd.
Original language | English |
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Pages (from-to) | 844-850 |
Number of pages | 7 |
Journal | Neurochemistry International |
Volume | 57 |
Issue number | 7 |
DOIs | |
State | Published - Dec 2010 |
ASJC Scopus Subject Areas
- Cellular and Molecular Neuroscience
- Cell Biology
Keywords
- Edema
- Geldanamycin
- Intracerebral hemorrhage
- Neurobehavior
- Neuroprotection
- Lactams, Macrocyclic/pharmacology
- Up-Regulation/physiology
- Male
- Random Allocation
- Brain Injuries/etiology
- Cerebral Hemorrhage/complications
- HSP72 Heat-Shock Proteins/biosynthesis
- Animals
- HSP70 Heat-Shock Proteins/biosynthesis
- Mice
- Benzoquinones/pharmacology
- Disease Models, Animal