TY - JOUR
T1 - The platelet-activating factor antagonist BN 52021 attenuates hypoxic- ischemic brain injury in the immature rat
AU - Liu, Xiao Hong
AU - Eun, Baik Lin
AU - Silverstein, Faye S.
AU - Barks, John D.E.
PY - 1996/12
Y1 - 1996/12
N2 - Platelet-activating factor (PAF) is overproduced in ischemic brain. Although postischemic PAF antagonist administration protects the mature brain in some models, little is known about the effects of PAF antagonists in the immature brain. We hypothesized that the PAF antagonist BN 52021 would attenuate perinatal cerebral hypoxic-ischemic injury. To elicit focal hypoxic-ischemic brain injury, 7-d-old (P7) rats (n = 111) underwent right carotid ligation, followed by 2.5-3.25 h of hypoxia (fractional concentration of inspired O2 = 0.08). BN 52021 neuroprotection was evaluated in three groups of experiments: 1) 25 mg/kg/dose, 0 and 2 h posthypoxia: 2), 25 mg/kg/dose immediately before and 1 h after hypoxia; and 3) posthypoxia- ischemia treatment with BN 52021 12.5, 25, or 50 mg/kg/dose in 2 doses 0 and 2 h after hypoxia. All experiments included concurrent vehicle-injected controls. To quantitate severity of injury, bilateral regional cross- sectional areas (groups 1 and 2) or hemisphere weights (group 3) were evaluated on P12. Both pre- and posthypoxic treatment with BN 52021 (25 mg/kg/dose, two serial doses) decreased the incidence of cerebral infarction from 90% to about 30% (p < 0.02, Fisher's exact test). Measurement of cross- sectional areas confirmed neuroprotection and indicated some benefit of pre- over posthypoxic ischemic treatment in hippocampus and cortex. Over the dose range tested, the neuroprotective effect of BN 52021 administration was not dose-dependent. In contrast, BN 52021 did not attenuate N-methyl-D-aspartate induced hippocampal excitotoxic injury in P7 rats. Either prophylactic or 'rescue' administration of PAF antagonists decreases the incidence and severity of brain injury associated with an episode of perinatal cerebral hypoxia-ischemia.
AB - Platelet-activating factor (PAF) is overproduced in ischemic brain. Although postischemic PAF antagonist administration protects the mature brain in some models, little is known about the effects of PAF antagonists in the immature brain. We hypothesized that the PAF antagonist BN 52021 would attenuate perinatal cerebral hypoxic-ischemic injury. To elicit focal hypoxic-ischemic brain injury, 7-d-old (P7) rats (n = 111) underwent right carotid ligation, followed by 2.5-3.25 h of hypoxia (fractional concentration of inspired O2 = 0.08). BN 52021 neuroprotection was evaluated in three groups of experiments: 1) 25 mg/kg/dose, 0 and 2 h posthypoxia: 2), 25 mg/kg/dose immediately before and 1 h after hypoxia; and 3) posthypoxia- ischemia treatment with BN 52021 12.5, 25, or 50 mg/kg/dose in 2 doses 0 and 2 h after hypoxia. All experiments included concurrent vehicle-injected controls. To quantitate severity of injury, bilateral regional cross- sectional areas (groups 1 and 2) or hemisphere weights (group 3) were evaluated on P12. Both pre- and posthypoxic treatment with BN 52021 (25 mg/kg/dose, two serial doses) decreased the incidence of cerebral infarction from 90% to about 30% (p < 0.02, Fisher's exact test). Measurement of cross- sectional areas confirmed neuroprotection and indicated some benefit of pre- over posthypoxic ischemic treatment in hippocampus and cortex. Over the dose range tested, the neuroprotective effect of BN 52021 administration was not dose-dependent. In contrast, BN 52021 did not attenuate N-methyl-D-aspartate induced hippocampal excitotoxic injury in P7 rats. Either prophylactic or 'rescue' administration of PAF antagonists decreases the incidence and severity of brain injury associated with an episode of perinatal cerebral hypoxia-ischemia.
UR - http://www.scopus.com/inward/record.url?scp=0029852757&partnerID=8YFLogxK
U2 - 10.1203/00006450-199612000-00004
DO - 10.1203/00006450-199612000-00004
M3 - Article
C2 - 8947953
AN - SCOPUS:0029852757
SN - 0031-3998
VL - 40
SP - 797
EP - 803
JO - Pediatric Research
JF - Pediatric Research
IS - 6
ER -