Expression of EMAP-II by activated monocytes/microglial cells in different regions of the rat hippocampus after trimethyltin-induced brain damage.
Endothelial monocyte-activating polypeptide-II (EMAP-II), a novel cytokine with proinflammatory and antiangiogenic properties, has previously been shown to be expressed by activated monocytes/microglial cells in the rat brain and was therefore considered a useful marker to stage microglial activation in inflammatory lesions. The aim of the present immunohistochemical study was to investigate expression of EMAP-II in the rat hippocampus after intoxication with the organotin compound trimethyltin (TMT). Administration of this neurotoxicant is known to produce brain damage mainly affecting the hippocampal formation, with severe neuronal cell loss being observed predominantly in regions CA-1 and CA-3. The maximum severity of TMT-induced brain damage is observed 21 days after a single ip administration. In this well-characterized model of neurodegeneration, activated microglial cells have been described to occur mainly in the early stages of TMT-induced neurotoxicity. Following TMT intoxication, we observed a significant increase in EMAP-II(+) monocytes/microglial cells in the CA-1 and the CA-3 regions. The CA-2 region, however, was largely spared. While appearance of single EMAP-II(+) microglial cells was observed already after 5 days, EMAP-II immunoreactivity reached its maximum after 21 days and persisted in some of the rats up to 35 days. These findings show a close correlation to the temporal and spatial pattern of neuronal damage described in the rat hippocampus after TMT administration previously. Thus, upregulation of EMAP-II by activated monocytes/microglial cells may serve as a sensitive marker of neurotoxic lesions in the rat brain.
Brabeck
Christine
C
Institute of Brain Research, University of Tuebingen, Calwer Strasse 3, D-72076, Tuebingen, Germany.
Michetti
Fabrizio
F
Geloso
Maria Concetta
MC
Corvino
Valentina
V
Goezalan
Fatma
F
Meyermann
Richard
R
Schluesener
Hermann J
HJ
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000139:chemically induced* / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014298:Trimethyltin Compounds / Q000633:toxicity*
D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D014298:Trimethyltin Compounds; C077219:small inducible cytokine subfamily E, member 1; C046488:trimethyltin