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Transcriptional regulation of inflammatory and extracellular matrix-regulating genes in experimental subarachnoid cerebral arteries following hemorrhage in rats

Författare

Summary, in English

Object. Subarachnoid hemorrhage (SAH) results in the expression of inflammatory and extracellular matrix (ECM)related genes and various G protein-coupled receptors. In the present study, the authors evaluated the time course and sequence of the transduction pathways, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase-1 and 2 (ERK1/2), and associated transcription factor activation as well as gene regulation and associated protein levels. Methods. Subarachnoid hemorrhage was induced in rats by injecting 250 mu l of blood into the suprachiasmatic cistern, and gene regulation in the cerebral arteries was examined at various points in time following SAH by using quantitative polymerase chain reaction (PCR) and immunohistochemistry. Results. Immunohistochemical findings demonstrated that SAH phosphorylates and activates p38 and ERK1/2 as well as the downstream transcription factors Elk-1 and activating transcription factor-2. The pattern of activation consists of a rapid phase within the first few hours and a late phase that occurs from 24 to 48 hours. Activation is followed by an increase in the transcription of the inflammatory and ECM-related genes (IL6, TNF alpha, IL1 beta, CXCL1, CXCL2, CCL20, MMP8, MMP9, MMP13, and iNOS), as demonstrated using real-time PCR. For MMP13 and iNOS, the changes in transcription were translated into functional proteins, as revealed on immunohistochemistry. Conclusions. Activation of the p38 and ERK1/2 signaling pathways and their downstream transcription factors can explain the increase in the transcription of the genes studied. This increase and the subsequent augmentation in protein levels suggest that the inflammatory response may in part explain the remodeling that occurs in cerebral arteries following SAH.

Publiceringsår

2007

Språk

Engelska

Sidor

1015-1022

Publikation/Tidskrift/Serie

Journal of Neurosurgery

Volym

107

Issue

5

Dokumenttyp

Artikel i tidskrift

Förlag

American Association of Neurosurgeons

Ämne

  • Other Clinical Medicine

Nyckelord

  • 5-HT1B RECEPTOR
  • UP-REGULATION
  • VASOSPASM
  • EXPRESSION
  • BRAIN
  • APOPTOSIS
  • CYTOKINES
  • MODELS
  • CELLS
  • BLOOD-FLOW
  • mitogen-activated protein kinase
  • extracellular matrix
  • inflammation
  • subarachnoid hemorrhage

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 0022-3085