Treatment with docosahexaenoic acid after hypoxia-ischemia improves forepaw placing in a rat model of perinatal hypoxia-ischemia

Abstract

Objective: Docosahexaenoic acid (DHA) is a dietary fatty acid with neuroprotective properties. We hypothesized that DHA treatment after hypoxia-ischemia would improve function and reduce brain volume loss in a perinatal rat model.

Study design: Seven-day-old Wistar rat pups from 7 litters (n = 84) underwent right carotid ligation, followed by 8% O(2) for 90 minutes. Fifteen minutes after hypoxia-ischemia, pups were divided into 3 treatment groups (intraperitoneal injections of DHA 1, 2.5, or 5 mg/kg) and 2 control groups (25% albumin or saline). At 14 days, rats underwent vibrissae-stimulated forepaw placing testing, and bilateral regional volumes were calculated for cortex, striatum, hippocampus, and hemisphere.

Results: Posthypoxia-ischemia treatment with DHA acid significantly improved vibrissae forepaw placing (complete responses: 8.5 ± 2 treatment vs 7.4 ± 2 controls; normal = 10; P = .032, t test). Postinjury DHA treatment did not attenuate brain volume loss in any region.

Conclusion: Posthypoxia-ischemia DHA treatment significantly improves functional outcome.

Figure 1. DHA Treatment after hypoxia ischemia attenuates forepaw placing deficits among hypoxic ischemic pups

Vibrissae-stimulated forepaw placing (10 trials/side) was evaluated on postnatal-day-14 (P14) in pups that underwent right carotid ligation followed by 90 minutes of hypoxia at 8% oxygen followed by administration of treatment (DHA 1mg/kg, 2.5mg/kg or 5mg/kg) or control (albumin, normal saline (NS)) on P7. The y-axis represents the weighted response score (see Methods; best possible score is 20). Boxes represent interquartile range; horizontal bars represent medians. Whiskers extend to data points no more than 1.5 width of box. There is an overall beneficial effect of DHA treatment when comparing pooled treatment (3 DHA doses) with pooled control groups (NaCl and Albumin (p = 0.035, t-test). ** Vibrissae scores are significantly better with DHA 2.5 mg/kg than 1 mg/kg or either control group (p = 0.032, Tukey Kramer). Because there is minimal variability in treatment groups, the circles represent the artificial distinction of outlier and stars represent extreme values.