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

In this study we evaluated the activation of the cytokine and growth factor responsive transcription factors signal transducer and activator of transc ription 3 (STAT3) and nuclear factor kappa B (NF kappa B) after different g rades of neural damage in the immature rat brain using double immunocytoche mical 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. Inte restingly, activation of both transcription factors is only observed in cor tical areas affected by severe tissue damage, neuronal degeneration, and bl ood-brain barrier (BBB) disruption. In contrast, the milder glial response occurring in the distal thalamus is not preceded by immunocytochemically de tectable STAT3 and NF kappa B activation, although microglial response, ast roglial hypertrophy, and glial fibrillary acidic protein (GFAP) overexpress ion do occur. In the cortex, astrocytes show STAT3 and NF kappa B activatio n already at 2 to 4 hours post-lesion, preceding cell hypertrophy and GFAP upregulation, and being maintained in the long-term formed glial scar. STAT 3 and NF kappa B activation in microglial cells is protracted and observed at 10 to 24 hours pst-lesion. The early activation of both transcription fa ctors in astroglial cells could contribute to the changes in gene expressio n leading to astrogliosis and the release of signalling molecules which may contribute to the subsequent activation of these transcription factors in microglial cells.