STAT3 and NFκB activation precedes glial reactivity in the excitotoxically injured young cortex but not in the corresponding distal thalamic nuclei

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

Abstract

In this study we evaluated the activation of the cytokine and growth factor responsive transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) after different grades of neural damage in the immature rat brain using double immunocytochemical techniques and electron microscopy. Following neocortical N-methyl-D-aspartate induced excitotoxic cell death, both these transcription factors are mainly activated in astrocytes, although microglia, endothelial cells, and neurons show transient activation at specific times and locations. Interestingly, activation of both transcription factors is only observed in cortical areas affected by severe tissue damage, neuronal degeneration, and blood-brain barrier (BBB) disruption. In contrast, the milder glial response occurring in the distal thalamus is not preceded by immunocytochemically detectable STAT3 and NFκB activation, although microglial response, astroglial hypertrophy, and glial fibrillary acidic protein (GFAP) overexpression do occur. In the cortex, astrocytes show STAT3 and NFκB activation already at 2 to 4 hours post-lesion, preceding cell hypertrophy and GFAP upregulation, and being maintained in the long-term formed glial scar. STAT3 and NFκB activation in microglial cells is protracted and observed at 10 to 24 hours post-lesion. The early activation of both transcription factors in astroglial cells could contribute to the changes in gene expression leading to astrogliosis and the release of signalling molecules which may contribute to the subsequent activation of these transcript, ion factors in microglial cells.
Original languageEnglish
Pages (from-to)151-163
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number2
DOIs
Publication statusPublished - 1 Jan 2000

Keywords

  • Astrocyte
  • Development
  • Glial response
  • Microglia
  • Neuronal injury
  • Transcription factor

Fingerprint

Dive into the research topics of 'STAT3 and NFκB activation precedes glial reactivity in the excitotoxically injured young cortex but not in the corresponding distal thalamic nuclei'. Together they form a unique fingerprint.

Cite this