Endothelinergic signaling during recovery of brain cortical lesions.

CASTAÑEDA M; CUBILLA, MA; BACHOR, TP; SUBURO, A.M.

NEUROLOGICAL RESEARCH.

MANEY PUBLISHING

Lugar: Leeds; Año: 2011 vol. 33 p. 137 - 144

0161-6412

1. Objectives. Recovery of brain lesions has been associated with increased activation and migration of endogenous neural stem cells, glia, and endothelium. To understand the role of endothelinergic signaling in these phenomena we studied devascularizing lesions of mouse brain cortex. Our specific aims were to (a) describe the endothelinergic cell phenotypes appearing within the lesions and (b) evaluate the effect of endothelinergic blockade on the injured cortex. 2. Methods. C57Bl/6 mice were anesthetized and submitted to devascularization lesions of the right M1 cortical area. A group of mice was daily treated with tezosentan, a dual endothelinergic receptor blocker. Mice were euthanatized 5 days after surgery and the injured area was studied with immunohistochemistry for endothelin (ET), endothelin receptor B (ETRB), glial fibrillary acidic protein (GFAP), prominin-1 (PRO), nestin (NES) and phospho-histone H3 (pHH3). 3. Results. The injured cortex exhibited a large increase of multipolar ET+, ETRB+, GFAP+, PRO+, and NES+ cells. These markers appeared in different combinations. ET+/ETRB+ cells always showed GFAP, whereas PRO was only found in ET+/ETRB+ cells. Tezosentan treatment reduced the perilesional expression of GFAP and decreased the number of proliferating cell nuclei displaying pHH3. 4. Discussion. Our observations suggest that endothelinergic cells surrounding the lesion belong to a mixed population including reactive glia and neural progenitor cells. Findings in tezosentan-treated mice probably reflect a decrease of reactive gliosis with a still unknown effect on neural progenitor cells (aceptado para su publicación en 2010, publicado en marzo de 2011).