Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage

Paul Matz, Christopher Turner, Philip R. Weinstein, Stephen M. Massa, S. Scott Panter, Frank R Sharp

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The heme released following subarachnoid hemorrhage is metabolized by heme-oxygenase (HO) to biliverdin and carbon monoxide (CO) with the release of iron. The HO reaction is important since heme may contribute to vasospasm and increase oxidative stress in cells. HO is comprised of at least two isozymes, HO-2 and HO-1. HO-1, also known as heat shock protein HSP32, is inducible by many factors including heme and heat shock. HO-2 does not respond to these stresses. To begin to examine HO activity following subarachnoid hemorrhage (SAH), the expression of HO-1 and HO-2 was investigated after experimental SAH in adult rats. Immunocytochemistry for HO-1, HO-2 and HSP70 proteins was performed at 1, 2, 3 and 4 days after injections of lysed blood, whole blood, oxyhemoglobin and saline into the cisterna magna. A large increase in HO-1 immunoreactivity was seen in cells throughout brain following injections of lysed blood, whole blood, and oxyhemoglobin but not saline. Lysed blood, whole blood and oxyhemoglobin induced HO-1 in all of the cortex, hippocampus, striatum, thalamus, forebrain white matter and in cerebellar cortex. HO-1 immunoreactivity was greatest in those regions adjacent to the basal subarachnoid cisterns where blood and oxyhemoglobin concentrations were likely highest. Double immunofluorescence studies showed the HO-1 positive cells to be predominately microglia, though HO-1 was induced in some astrocytes. HO-1 expression resolved by 48 h. HO-2 immunoreactivity was abundant but did not change following injections of blood. A generalized induction of HSP70 heat shock protein was not observed following injections of lysed blood, whole blood, oxyhemoglobin, or saline. These results suggest that HO-1 is induced in microglia throughout rat brain as a general, parenchymal response to the presence of oxyhemoglobin in the subarachnoid space and not as a stress response. This microglial HO-1 response could be protective against the lipid peroxidation and vasospasm induced by hemoglobin, by increasing heme clearance and iron sequestration, and enhancing the production of the antioxidant bilirubin.

Original languageEnglish (US)
Pages (from-to)211-222
Number of pages12
JournalBrain Research
Volume713
Issue number1-2
DOIs
StatePublished - Mar 25 1996
Externally publishedYes

Fingerprint

Heme Oxygenase-1
Subarachnoid Hemorrhage
Neuroglia
Oxyhemoglobins
Brain
Heme Oxygenase (Decyclizing)
Heme
Injections
Microglia
Iron
Biliverdine
Cisterna Magna
Subarachnoid Space
Cerebellar Cortex
HSP70 Heat-Shock Proteins
Carbon Monoxide
Prosencephalon
Heat-Shock Proteins
Thalamus
Bilirubin

Keywords

  • bilirubin
  • heat shock protein
  • heme-oxygenase
  • hemoglobin
  • stress protein
  • subarachnoid hemorrhage

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage. / Matz, Paul; Turner, Christopher; Weinstein, Philip R.; Massa, Stephen M.; Panter, S. Scott; Sharp, Frank R.

In: Brain Research, Vol. 713, No. 1-2, 25.03.1996, p. 211-222.

Research output: Contribution to journalArticle

Matz, Paul ; Turner, Christopher ; Weinstein, Philip R. ; Massa, Stephen M. ; Panter, S. Scott ; Sharp, Frank R. / Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage. In: Brain Research. 1996 ; Vol. 713, No. 1-2. pp. 211-222.
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