Angiotensin II AT2 receptor blocker reverses the neuroprotective action of preconditioning in the brain of hypoxic-ischemic neonatal rats.

LÓPEZ AGUILERA F; VERÓNICA BIAGGIO; CAROLINA AYALA; ALICIA M SELTZER

Huerta Grande, Córdoba

Congreso; XXVI Reunión Anual Sociedad Argentina de Investigación en Neurociencias; 2011

Sociedad Argentina de Investigación en Neurociencias

AT2 receptors (AT2-R) are involved in the control of cell proliferation and tissue regeneration. In a previous report we observed that AT2-R were up-regulated in the preconditioned neonatal brain after ischemia, and their activation  could be neuroprotective contributing to the beneficial effects of AT1 receptor antagonists on neurological outcome of cerebral ischemia. Seven- day old WKY rat pups were submitted to preconditioning (PC) and then to common carotid unilateral artery ligation (I) / 2 min asphyxia on day 8 (H). The lesioned group (L) was submitted only to I/H. A third group was PC+I/H and injected 5 µl of PD123319 (1.69mM) in the lateral ventricle after PC. Control animals received mock treatment. The animals were sacrificed at 7 days post lesion (PND15). Ki67 (a marker of cell proliferation) and GFAP (reactive astrocytes) were analyzed by IHQ (DAB). The treatment with the AT2 blocker reversed the effects of preconditioning, increasing the GFAP+ label (p<0.001 vs PC) in both hemispheres and dampening the increase of Ki67+ unidentified cells in the area of lesion (p <0.01 vs. PC).We hypothesize that AT2 receptors may participate in the neuroprotective action of preconditioning by direct or indirect regulatory actions on the AT1 receptors. Subsidio ANPCyT, PICT 2006-451.