Docosahexaenoic acid pretreatment confers neuroprotection in a rat model of perinatal cerebral hypoxia-ischemia

Abstract

Objective-Lipopolysaccharide (LPS) pretreatment potentiates HI injury. We hypothesized that docosahexaenoic acid (DHA) pretreatment would improve function and reduce brain damage in this rat model of perinatal brain injury and inflammation.Study Design-Seven-day-old Wistar rats were divided into 3 groups. One received intraperitoneal (IP) DHA 1 mg/kg and LPS 0.1mg/kg. The second received 25% Albumin and LPS. The third received normal saline (NS). Injections were given 2.5 hours prior to right carotid ligation, followed by 90 minutes 8% O 2 . Rats underwent sensorimotor testing and brain damage assessment on P14.Results-DHA pretreatment improved forepaw placing compared to albumin/LPS. (Mean±SD successes/10 trials: 8.57±1.7 DHA/LPS vs 6.72±2.2 Albumin/LPS, p<.0009). There were no significant differences in brain damage among groups.Conclusions-Inflammatory stimulation before HI resulted in poorer function than HI alone. Although DHA pretreatment had no impact on brain damage, it significantly improved function in neonatal rats exposed to LPS and HI.

Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

“…Remarkably, DHA-pretreated animals exhibited extensive movements in all three joints and weight-supported steps at 7 dpi. Our findings are supported by studies showing that pretreatment with polyunsaturated fatty acids (PUFAs) provides tolerance against ischemic-induced neurodegeneration (Blondeau et al, 2002), reduces disabilities after traumatic brain injury in rats (Wu et al, 2004), confers neuroprotection from brain hypoxia-ischemia (Berman et al, 2009), and increases resistance to pentylenetetrazol-induced seizures (Taha et al, 2010).…”

Docosahexaenoic Acid Augments Hypothermic Neuroprotection in a Neonatal Rat Asphyxia Model

“…DHA (Sigma-Aldrich, St. Louis, MO) was complexed to human 25% albumin, as previously described (final concentration 0.5 mg/1 ml) [4]. The dose selected, 2.5 mg/kg, was more effective than either higher (5 mg/kg) or lower (1 mg/kg) doses in the post-HI treatment protocol reported previously [5].…”

“…DHA modulates neuroinflammation, oxidative stress, and apoptosis [7-9]. We previously reported that DHA pre-treatment is neuroprotective in a neonatal rodent model of hypoxic-ischemic (HI) brain injury, elicited by right carotid artery ligation and timed exposure to 8% oxygen in 7 day old (P7) rats [4]; a single injection of DHA prior to lesioning improved sensorimotor function and reduced brain damage. Subsequently, we found that a single DHA injection after the end of hypoxia exposure improved the same neurologic function but did not reduce tissue injury [5].…”

The protective effect of docosahexaenoic acid on the bilirubin neurotoxicity

“…DHA is an especially promising therapeutic or preventive intervention because it may simultaneously exert beneficial effects on several of the injury cascades contributing to perinatal brain injury, including free radicals, inflammatory cytokines, bioactive lipid mediators, and apoptosis 21,[24][25][26] . Berman et al (2009) showed that DHA had neuroprotective and restorative effects in their animal models 27 . Although the role of DHA in bilirubininduced brain injury is unknown, DHA is known to have neuroprotective effects against oxidative stress and apoptosis.…”

“…These includes heart disease, cancer, immune problems, neuronal functions, aging and "other" hard to categorize problems such as migraine headaches, malaria and sperm infertility 40 . Berman et al (2009) have shown that DHA pretreatment provides effective neuroprotection to the neonatal rat brain, improving functional testing to near-normal levels and reducing brain volume loss, particularly in the hippocampus, in perinatal hypoxia-ischemia animal model 27 . Furthermore, DHA is reported to play a neuroprotective role against oxidative stress in photoreceptors and to be important both for the maturation of retinal photoreceptors and for preventing photoreceptor apoptosis in the developing retina 25,41,42 .…”