Text Box: ROLE OF P-SELECTIN ON HYPOXIC-ISCHEMIC BRAIN INJURY IN NEONATAL RATS Eun BL1, Kim KB2, Pee DH1, Tockgo YC1 Department of Pediatrics, College of Medicine, Korea University1, Kwandong University2, Seoul, Korea Objective: Leukocyte-endothelial adhesion is a key step in the initiation of post-ischemic reperfusion injury in many organ systems. We hypothesizes that P-selectin might mediate post-hypoxic-ischemic (HI) injury in immature rat brain. Methods: To elicit focal hypoxic-ischemic brain injury, seven day old (P7) rats (n=160) underwent right carotid coagulation, followed by 2 h hypoxia (FiO2=0.08). For RNA extraction, the rats (n=28) were decapitated at 0, 2, 4, 8, 12, 24 and 48 h after hypoxic-ischemic injury. For Western blot analyses with P-selectin, rats (n=37) were decapitated at 0, 15, 30 min, 1, 2, 4, 8, 12, 24 and 48 h after hypoxic-ischemic injury. To test the efficacy of pretreatment regimen, P7 rats (n=59) received fucoidin immediately before and again after hypoxia intraperitoneally with a 26 gauge needle. Results: P-selectin mRNA expression in the ipsilateral (right) hemisphere reached a peak at 8 h after HI and then barely detected after 24 h. P-selectin protein was detected as early as 15 min and 30 min at both hemisphere in experimental rats and decreased at 1 h, and increased in right hemisphere at 4 h post-HI, peaked at 8 h and no longer detectable at 24 h. We found substantial neuroprotective effect after pretreatment with fucoidin as a dose dependency. Conclusions: The temporal profiles of post-HI P-selectin mRNA and protein expression are consistent with a role in the evolution of subsequent brain injury. Potential of therapeutic application of P-selectin blockade or similar anti-adhesion strategies may reduce the brain damage after perinatal HI. 2002