Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood

Christopher P. Turner, S. Scott Panter, Frank R Sharp

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The initial aim of this study was to determine if the HSP70 (the main inducible heat shock protein), HO-1 (heme oxygenase-1, HSP32) and HSP47 (a collagen chaperone) stress proteins were induced in the same focal regions of rat brain following experimental subarachnoid hemorrhage (SAH). The next objective was to determine whether anti-oxidants prevented the stress gene expression in the focal regions. Lysed blood (150 μl) was injected into the subarachnoid space of adult, female Sprague-Dawley rats via the cisterna magna. Animals were sacrificed 24 h later. Immunocytochemistry showed focal regions of stress gene induction in most animals (13/21), HSP70 and HO-1 proteins being expressed in neurons, microglia and astrocytes and HSP47 being expressed in microglia. Co-induction of the same three stress proteins was observed in focal areas in the striatum and cerebellum as well. In the 13 animals with focal regions of stress gene induction there were 8.1 ± 1.8 foci in cortex, 5.5 ± 0.9 foci in striatum, and 11.7 ± 7.3 foci in cerebellum in the brain of each animal. The focal regions of stress gene induction varied in size from 200 μm to 7 mm in diameter. Systemic administration of the tirilazad-like anti-oxidants U101033E (n = 8) and U74389G (n =7) completely blocked stress protein induction in focal brain regions normally produced by cisternal injections of lysed blood. There were fewer drug treated animals (0/15) with focal areas of stress gene induction compared to non-drug (13/21) treated animals following the cisternal lysed blood injections (p < 0.01 using Fisher's probability test). This study shows that anti-oxidants prevent focal regions of injury as assessed by heat shock protein expression in a rat mode of SAH.

Original languageEnglish (US)
Pages (from-to)87-102
Number of pages16
JournalMolecular Brain Research
Volume65
Issue number1
DOIs
StatePublished - Feb 19 1999
Externally publishedYes

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Keywords

  • Anti- oxidant
  • Heat shock protein
  • Heme oxygenase
  • HSP70
  • Intracerebral hemorrhage
  • Oxidative stress
  • Stress protein
  • Stroke
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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