HYPOXIC PRECONDITIONING INDUCED BY INTERMITTENT HYPOXIA IN AN EXPERIMENTAL MODEL OF SLEEP APNEA

AVILES REYES RX; ANGELO MF; UNSAIN N; VILLARREAL A; BARKER PA; RAMOS AJ

Congreso; 42nd annual meeting of the American Society for Neurochemistry; 2011

ASN

Sleep apnea (SA) and cerebral ischemia are serious public health pro­blems in adult population having high prevalence, morbility and mortality. Clinical studies have shown that SA patients have reduced mortality after an ischemic stroke. The neuro­pro­tection induced by hypo­xic preconditioning (HP); support the fact that the brain can adapt to insults such as ischemia, thus increasing the chances of survival from subsequent injury. To test this hypo­thesis, we exposed adult rats or mice (wild type wt, XIAP-/- or NF-kB reporter) to SA model of inter­mittent hypo­xia (IH) by cycling oxygen level (6 min 21% + 6 min 10%; 3 and 5 days; 8 h/day), in the sleep phase (Hx group). Control animals were exposed to room air (Nx). A subgroup of animals exposed to 3-5 days of HI or Nx were then subjected to ischemia by cortical devascularization (groups Hx+I or Nx+I). Our results showed that astrogliosis (analyzed by GFAP+ and Vimentin+) was diminished in animals previously exposed to Hx+I. Reduced number of altered neuro­ns were observed in Hx+I compared with Nx+I group. Fluoro Jade B staining showed a reduced number of degenerating neuro­ns in the Hx+I animals. XIAP-/- mice lost this pro­tection to subsequent ischemia induced by the Hx exposure. RT-PCR studies showed the Heat Shock Proteins (HSP) mRNAs induction was increased in Hx exposed animals. The NF-êB activity was increased in Hx animals as shown by the NF-êB reporter trans­genic mice and increased levels of IêB in wt mice. The inhibitor of apoptosis pro­teins (IAPs) specifically c-IAP, XIAP and Bcl-XL showed an increase in Hx animals. XIAP -/- mice showed limited expression of HSPs and IAPs. We conclude that IH develop a degree of cellular brain adaptation or tolerance that induces partial neuro­pro­tection to a subsequent ischemic injury, supporting clinical observations from SA patients, pro­bably are involving HSPs and NF-kB target genes specifically XIAP.