Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage

Anatol Manaenko, Nancy Fathali, Hank Chen, Hidenori Suzuki, Shammah Williams, John H. Zhang, Jiping Tang

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)844-850
Number of pages7
JournalNeurochemistry International
Volume57
Issue number7
DOIs
StatePublished - 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

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