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Docosahexaenoic acid (DHA) is a dietary polyunsaturated fatty acid with neuroprotective properties. We hypothesized that DHA treatment after hypoxia-ischemia (HI) would improve functional outcome and reduce brain volume loss in a rat model of perinatal HI.
Seven-day-old Wistar rat pups from 8 litters (N=96) were divided into 3 treatment groups and 2 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 or normal saline (NaCl). Pups underwent right carotid ligation followed by 1.5 hours recovery at 37°C, then 90 minutes in 8% O2 to simulate cerebral HI. Fifteen minutes after HI, pups received control or treatment IP injections. At 14 days, rats underwent bilateral sensorimotor testing using vibrissae-stimulated forepaw placing response. Bilateral hemisphere and regional volumes were calculated from cortex, striatum, and hippocampus, and right hemisphere volume loss was calculated [100*(L−R)/L)].
Post HI treatment with DHA significantly improved vibrissae forepaw placing response (16.9±0.8 treatment vs. 14.7±0.8 controls; normal function=20 p<.035, t-test). The predominant effect was limited to the two higher doses (Figure). Post injury DHA treatment did not attenuate brain volume loss in any region compared to controls.
Although brain volume loss is not affected by post-ischemia DHA treatment, treatment significantly improves functional outcome, particularly in higher doses.