34: DHA pretreatment confers neuroprotection in a rat model of perinatal hypoxia-ischemia


      Docosahexaenoic acid (DHA) is a readily-available dietary polyunsaturated fatty acid with anti-inflammatory and neuroprotective properties. We hypothesized that DHA pretreatment would improve functional outcome and reduce brain volume loss in a well-established rat model of perinatal hypoxia-ischemia (HI).

      Study Design

      Seven-day-old Wistar rat pups from 10 litters (N=120) were divided into 3 treatment groups and 3 control groups. Treatment groups received intraperitoneal (IP) injections of DHA 1, 2.5 or 5 mg/kg as DHA-albumin complex. Control groups received 25% albumin, normal saline or no IP injection. Injections were given 2.5 hours prior to right carotid ligation, which was followed by 1.5 hours recovery at 37°C, then 90 minutes in 8% O2, simulating cerebral HI. At 14 days, rats underwent bilateral sensorimotor testing using vibrissae-stimulated forepaw placing response, an accepted measure of functional behavioral development. Bilateral hemisphere and regional areas of cortex, striatum, and hippocampus were measured in regularly spaced sections; volumes were summed and right hemisphere volume loss was calculated [100*(L-R)/L)].


      DHA significantly attenuated brain volume loss compared to controls (p<.0001 ANOVA, factoring treatment and region). The most consistent effect was found in the hippocampus with 1 mg/kg dose (38% protection vs albumin controls). DHA pretreatment improved vibrissae forepaw placing response to near normal levels. (9.5±0.9 treatment vs. 7.1±2.2 controls; normal function=10 p<.0001, t-test). See Figure.


      DHA pretreatment improves functional outcome and reduces brain volume loss after HI in neonatal rats. Human trials are needed to test whether dietary DHA confers neuroprotection in pregnancies delivering at risk neonates.