Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats

The proinflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 rise during neuronal damage and activate the apoptotic mitogen-activated protein kinase p38. We studied apoptosis, the levels of TNF-alpha, IL-1 beta, and IL-6, and the cell type producing TNF-alpha in rats at 8, 10, and 14 days of age after neonatal exposure to glutamate, which induces neuronal damage. TNF-alpha production was significantly increased by glutamate, but inhibited by SB203580 (a p38 inhibitor). TNF-alpha, IL-1 beta, and IL-6 mRNA levels increased, but SB203580 did not modify their expression. Thus, the p38 signaling pathway influences the expression of inflammatory genes and its inhibition may offer anti-inflammatory therapy. (C) 2005 Elsevier B.V. All rights reserved.