Anti-inflammatory treatment with the p38 mitogen-activated protein kinase inhibitor SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen-glucose-deprived hippocampal slice cultures.
We investigated the effect of the p38 mitogen-activated protein kinase inhibitor SB239063 on inflammation and neurogenesis after ischemia in organotypic hippocampal slice cultures. Our study shows that after oxygen-glucose deprivation, the p38 mitogen-activated protein kinase (MAPK) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) are strongly activated. The p38 MAPK phosphorylation returned to basal levels within 1 h after oxygen-glucose deprivation, whereas the ERK1/2 phosphorylation reached the basal level only after 24 h. Treatment with 20 microM and 100 microM SB239063 strikingly reduced cell death after oxygen-glucose deprivation and significantly diminished microglia activation in the cornu ammonis (CA-region), but not in the area dentata. Levels of the pro-inflammatory cytokine IL-1beta were reduced by 84% after treatment with SB239063 whereas the cytokines IL-6 and TNF-alpha were not affected. After 6 days, neurogenesis was significantly increased in the posterior periventricle. Based on these findings, our study shows that anti-inflammatory treatment with SB239063 reduces cell death, inflammation and microglia activation and, at high concentrations, enhances the oxygen-glucose deprivation-induced neurogenesis in the posterior periventricle.
Strassburger
Maria
M
Research Institute for Applied Neuroscience (FAN) gGmbH, Leipziger Str. 44, D-39120 Magdeburg, Germany. maria.strassburger@web.de
Braun
Holger
H
Reymann
Klaus G
KG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009924:Organ Culture Techniques; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007093:Imidazoles; D018696:Neuroprotective Agents; D011743:Pyrimidines; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C406525:SB 239063; D005947:Glucose