INTRANASAL ADMINISTRATION OF ATF ATTENUATES HYPOXIC-ISCHEMIC WHITE MATTER DAMAGE IN NEONATAL MICE

MARIANO G CLAUSI, PASQUINI LA, PASQUINI JM.

St Louis, Missouri

Congreso; 42ND ANNUAL ASN MEETING; 2011

We have previously demonstrated that a single dose of apotransferrin (aTf) intracrianially injected (ICI) in rats at 3 days of age produces an accelerated oligodendroglial cell (OLc) maturation (Marta et. al. 2000). More recently, we have demonstrated that after hypoxic-ischemic (H/I) injury in rats at P7, aTf ICI protects oligodendroglial precursor cells (OPCs). We have investigated the possibility of using intranasal (IN) administration of aTf to repair the neonatal brain damaged after H/I. Ten-day old mice that underwent cerebral hypoxia-ischemia (H/I) were used throughout. We used  transgenic mice expressing the enhaced green fluorescent protein (GFP) under the 2´-3´-cyclic nucleotide 3´-phosphodiesterase (CNP-EGFP) promoter which allows an easy detection of cells belonging to the OLc linage. Immediately after the H/I insult a group of pups received the IN of aTfh (10 mg/ml) and another group recieved IN of vehicle. Control animals were used as well. We used aTfh in order to detect its presence by Western blot in protein lysates from mice olfactory bulbs and forebrains just 30 min after its IN administration. Brain changes were evaluated 5 and 15 days after H/I. Our results show that after H/I treatment there is a loss in OL as evaluated by CNP-EGFP expression and by immunohistochemistry using different specific markers. The IN administration of aTf prevents white matter damage evaluated by different parameters. These results suggest the possibility of using intranasal administration of aTf  for clinical treatment.