DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice

Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury. Methods: 10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8–9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA. Results: Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia. Conclusions: Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA

Effect of a Goal Attainment Nursing Program on Self-management and Blood Pressure Control in High-risk Hypertensive Patients in a Primary Care Unit

Objective: To determine the effects of goal attainment in nursing programs among hypertensive patients who are at high-risk to cardiovascular disease. Methods: A quasi-experimental study was conducted in a primary care unit setting. Eligible participants included hypertensive patients aged 35 years and above with poorly controlled blood pressure and accompanying risk factors for cardiovascular disease. Seventy-eight participants were divided evenly into two groups via simple random sampling. The experimental group participated in a 10-week program consisting of small group education/demonstration sessions focused on goal setting and self-management behavior. These participants also received a follow-up phone call and text messages that served as reminders/reinforcements. The control group received routine care only, which included appropriately consultation with health care providers. Results: The proportion of participants who achieved optimal blood pressure control (SBP < 140 mmHg) in the experimental group (80.6%) was greater than the control group (44.1%) (p-value < 0.05). In addition, the systolic blood pressure of the experimental group ( 131.33 mmHg, S.D. 12.09) was significantly lower than that of the control group ( 142.96 mmHg, S.D. 15.77) (p-value < 0.05). The mean scores for self-management behavior were significantly higher in the experimental group ( 106.14, S.D. 14.43) than the control group (  83.21, S.D. 8.17) (p-value < 0.05). Conclusion: The goal attainment nursing program targeting behavior modification through empowerment was effective in improving self-management behavior among hypertensive patients at high risk for cardiovascular disease. Thus, this program can be applied to patients with uncontrolled chronic diseases.

N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice.

We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O(2) for 15 minutes at 37°C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.1-0.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans

DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after Brain Hypoxia-Ischemia in Neonatal Mice.

Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism of this neuroprotection remains unclear. We hypothesized that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain injury.10-day-old C57BL/6J mice following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9 weeks of recovery, oxidative injury, neurofunctional and neuropathological outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the presence or absence of DHA or EPA.Only post-treatment with tri-DHA reduced oxidative damage and improved short- and long-term neurological outcomes. This was associated with increased content of DHA in brain mitochondria and DHA-derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro, hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia.Post-treatment with tri-DHA resulted in significant accumulation of DHA and DHA derived bioactive metabolites in the HI-brain. This was associated with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced oxidative brain injury and permanent neuroprotection. Interaction of DHA with mitochondria alters ROS release and improves Ca2+ buffering capacity. This may account for neuroprotective action of post-HI administration of tri-DHA

Long-term effect of Tri-DHA on cerebral tissue death at 8 wk after H/I.

<p>Mice were subjected to 15-min H/I and received 2 i.p. administrations of 0.375 g Tri-DHA/kg (n = 6) vs. saline (n = 5). At 8 wk after H/I mice were sacrificed and brains were fixed with 4% paraformaldehyde and 10 µm-thick slices were cut and preserved. Nissl staining was used for identifying neuronal and brain structure. As described in Methods right brain tissue loss in relation to the contralateral hemisphere was calculated and expressed as a percentage. Each bar represents the mean ± SEM. * <i>p</i><0.05.</p

Influence of Prolonged Whole Egg Supplementation on Insulin-like Growth Factor 1 and Short-Chain Fatty Acids Product: Implications for Human Health and Gut Microbiota

The gut microbiota exert a profound influence on human health and metabolism, with microbial metabolites playing a pivotal role in shaping host physiology. This study investigated the impact of prolonged egg supplementation on insulin-like growth factor 1 (IGF-1) and circulating short-chain fatty acids (SCFAs). In a subset of a cluster-randomized trial, participants aged 8–14 years were randomly assigned into three groups: (1) Whole Egg (WE)—consuming 10 additional eggs per week [n = 24], (2) Protein Substitute (PS)—consuming yolk-free egg substitute equivalent to 10 eggs per week [n = 25], and (3) Control Group (C) [n = 26]. At week 35, IGF-1 levels in WE significantly increased (66.6 ± 27.7 ng/mL, p p = 0.010). WE exhibited notable changes in the relative abundance of the Bifidobacterium and Prevotella genera. Strong positive SCFA correlations were observed with MAT-CR-H4-C10 and Libanicoccus, while Roseburia, Terrisporobacter, Clostridia_UCG-014, and Coprococcus showed negative correlations. In conclusion, whole egg supplementation improves growth factors that may be related to bone formation and growth; it may also promote benefits to gut microbiota but may not affect SCFAs

n-3 TG injection and cerebral blood flow after H/I.

<p>Cerebral blood flow (CBF) was measured by laser Doppler flowmetry (LDF) in neonatal mice after carotid artery ligation. Relative CBF was measured every two minutes during hypoxia in ipsilateral (right) hemispheres using a laser Doppler flowmeter. Changes in CBF in response to hypoxia were recorded for 20 min and expressed as percentage of the pre-hypoxia level for n-3 TG treated (n = 3) and saline treated (n = 5) neonatal mice.</p

Effect of Tri-DHA versus Tri-EPA on cerebral infarct volume after H/I.

<p>A. Mice were subjected to 15 min ischemia followed by 24-hr reperfusion and received 2 i.p. administrations (immediately after ischemia and 1 hr of reperfusion) at 2 doses (0.1 g n-3 TG/kg and 0.375 g n-3 TG/kg). Each bar represents the mean ± SEM of 5–7 independent experiments performed using the same H/I model. B. TTC-stained coronal sections of representative mouse brains from saline treated, 0.1 g Tri-DHA, 0.375 g Tri-DHA, 0.1 g Tri-EPA and 0.375 g Tri-EPA. * <i>p</i><0.05 compared to other groups except 0.1 g Tri-DHA/kg. ** <i>p</i><0.05 compared to other groups except 0.375 g Tri-DHA/kg and 0.375 g Tri-EPA/kg.</p

Blood TG and glucose levels after TG emulsion injections.

<p>A. Total plasma TG concentrations (mg/dL) in non-fasting neonatal mice (p10), acutely injected (i.p.) with saline or n-3 TG emulsion (0.75 g n-3 TG/kg body weight). *<i>p</i><0.05 (n = 3–8 in each group). Each data point represents the mean ± SEM of 3 separate experiments. B. Plasma glucose concentrations (mg/dL) in non-fasting mice (p10) in post-H/I treatment of n-3 TG or n-6 TG or vehicle (saline) comparing to the time between before H/I and after H/I. **<i>p</i><0.001 (n = 5–9 in each group).</p

Short term neurological outcomes.

<p>(A) Infarct volumes in HI+Veh (n = 30), HI+tri-EPA (n = 20), or HI+tri-DHA (n = 20) mice. (B) Representative TTC-stained cerebral sections from the same groups of mice. (C) Righting, and (D) Negative geotaxis reflex performance in naïve (n = 12); Veh+HI (n = 18); HI+tri-EPA (n = 13); and HI+tri-DHA (n = 18) mice.</p