Soman poisoning induces delayed astrogliotic scar and angiogenesis in damaged mouse brain areas.
Gliotic scar formation and angiogenesis are two biological events involved in the tissue reparative process generally occurring in the brain after mechanically induced injury, ischemia or cerebral tumor development. For the first time, in this study, neo-vascularization and glial scar formation were investigated in the brain of soman-poisoned mice over a 3-month period after nerve agent exposure (1.2 LD50 of soman). Using anti-claudin-5 and anti-vascular endothelial growth factor (VEGF) immunostaining techniques on brain sections, blood vessels were quantified and VEGF expression was verified to appraise the level of neo-angiogenesis induced in damaged brain areas. Furthermore, glial scar formation and neuropathology were estimated over time in the same injured brain regions by anti-glial fibrillary acidic protein (GFAP) immunohistochemistry and hemalun-phloxin (H&P) dye staining, respectively. VEGF over-expression was noticed on post-soman day 3 in lesioned areas such as the hippocampal CA1 field and amygdala. This was followed by an increase in the quantity of mature blood vessels, 3 months after soman poisoning, in the same brain areas. On the other hand, massive astroglial cell activation was demonstrated on post-soman day 8. Reactive astroglial cells were located only in damaged cerebral regions where H&P-stained eosinophilic neurons were found. For longer experimental times, astroglial response slowly decreased overtime but remained detectable on post-soman day 90 in some discrete brain regions (i.e. CA1 field and amygdala) evidencing the formation of a glial scar. In this study, we discuss the key role of VEGF in the angiogenic process and in the glial or neuronal response induced by soman poisoning.
Collombet
Jean-Marc
JM
Département de Toxicologie, CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 LA TRONCHE Cedex, France. jmcollombet@crssa.net
Four
Elise
E
Fauquette
William
W
Burckhart
Marie-France
MF
Masqueliez
Catherine
C
Bernabé
Denis
D
Baubichon
Dominique
D
Lallement
Guy
G
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D062507:Claudin-5; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012999:Soman / Q000506:poisoning*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D002800:Cholinesterase Inhibitors; D062507:Claudin-5; C491511:Cldn5 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D012999:Soman