Evidences of ischemic tolerance induced by a model of sleep apnea by intermittent hypoxia

AVILES REYES ROLANDO XAVIER; ANGELO MARI;A FLORENCIA; UNSAIN NICOLAS; VILLAREAL ALEJANDRO; PHIL BARKER; RAMOS ALBERTO JAVIER

Huerta Grande ¨C C¨®rdova Argentina

Congreso; II Reunion Conjunta de Neurociencias; 2010

Sleep apnea (SA) patients show reduced mortality after an ischemic stroke. This clinical observation probably evidences an ischemic tolerance phenomenon. To test this hypothesis, we exposed adult rats or mice (wild type, XIAP-/- or NF-kB reporter) to an experimental model of SA by intermittent hypoxia (IH) by cycling oxygen level (6 min 21% + 6 min 10%; 3 days; 8 h/day), during the sleep phase (Hx group). Control animals were exposed to room air (Nx). A subgroup of animals was subjected to a focal brain ischemia and sacrificed 3 or 7 days post lesion (dpl) (Nx+I or Hx+I). Our results showed that Heat Shock Proteins (HSP) mRNAs were significantly increased in hippocampus of Hx animals. Apoptosis Inhibitor Proteins (c-IAP, XIAP) showed an increase in Hx animals. The activity of NF-êB was increased in Hx animals as shown by the NF-êB reporter transgenic mice and increased levels of IkB. Reduced number of altered neurons with atypical NeuN staining in the ischemic penumbra were observed in Hx+I compared with Nx+I group. Fluoro Jade B staining also showed less number of degenerating neurons in the Hx+I wt animals. XIAP -/- mice lost the protection to a subsequent ischemia induced by Hx exposure. We conclude that IH induces partial protection to a following ischemia, probably involving HSPs and NF-kB target genes specifically XIAP.