Docosahexaenoic acid confers neuroprotection in a rat model of perinatal hypoxia-ischemia potentiated by Escherichia coli lipopolysaccharide-induced systemic inflammation.
OBJECTIVE
Lipopolysaccharide pretreatment potentiates hypoxic ischemic injury. We hypothesized that docosahexaenoic acid pretreatment would improve function and reduce brain volume loss in this rat model of perinatal brain injury and inflammation.


METHODS
Seven-day-old rats were divided into 3 groups: intraperitoneal docosahexaenoic acid 1 mg/kg and lipopolysaccharide 0.1 mg/kg, 25% albumin and lipopolysaccharide, and normal saline. Injections were given 2.5 hours before carotid ligation, followed by 90 minutes 8% O2. Rats underwent sensorimotor function testing and brain volume loss assessment on postnatal day 14.


RESULTS
Docosahexaenoic acid pretreatment improved vibrissae forepaw placing scores compared with albumin/lipopolysaccharide (mean+/-standard deviation weighted score/20: 17.72+/-0.92 docosahexaenoic acid/lipopolysaccharide vs 13.83+/-0.82 albumin/lipopolysaccharide; P<.007). Albumin/lipopolysaccharide rats scores were worse than those of the normal saline/normal saline rats (13.83+/-0.82 vs 17.21+/-0.71; P=.076). No significant differences in brain volume loss were observed among groups.


CONCLUSIONS
Lipopolysaccharide inflammatory stimulation in conjunction with hypoxic ischemic resulted in poorer function than hypoxic ischemic alone. Docosahexaenoic acid pretreatment had significantly improved function in neonatal rats exposed to lipopolysaccharide and hypoxic ischemic.
Berman
Deborah R
DR
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI.
Liu
Yi Qing
YQ
Barks
John
J
Mozurkewich
Ellen
E
D000818:Animals; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004926:Escherichia coli; D020925:Hypoxia-Ischemia, Brain / Q000517:prevention & control*; D016014:Linear Models; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids