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Docosahexaenoic Acid therapy of experimental ischemic stroke.

Belayev L, Khoutorova L, Atkins KD, Eady TN, Hong S, Lu Y, Obenaus A, Bazan NG - Transl Stroke Res (2010)

Bottom Line: Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h.Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points.Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo.

View Article: PubMed Central - PubMed

ABSTRACT
We examined the neuroprotective efficacy of docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, in acute ischemic stroke; studied the therapeutic window; and investigated whether DHA administration after an ischemic stroke is able to salvage the penumbra. In each series described below, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo). In series 1, DHA or saline was administered i.v. at 3, 4, 5, or 6 h after stroke. In series 2, MRI was conducted on days 1, 3 and 7. In series 3, DHA or saline was administered at 3 h, and lipidomic analysis was conducted on day 3. Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h. Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points. Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo. DHA administration provides neurobehavioral recovery, reduces brain infarction and edema, and activates NPD1 synthesis in the penumbra when administered up to 5 h after focal cerebral ischemia in rats.

No MeSH data available.


Related in: MedlinePlus

The characterization and quantification of 17-HDHA and NPD1 in the ipsilateral penumbra 3 days after MCAo. a–b The fragmentation pattern is depicted and c the quantification is presented. The increased content of 17-HDHA and of NPD1 in the ipsilateral penumbra in animals injected with DHA is consistent with the activation of the biosynthesis of NPD1. d Enzyme-mediated oxygenation of DHA for the biosynthesis of NPD1. Phospholipase A2 releases DHA from the second C position of phospholipids during brain ischemia-reperfusion. 15-Lipoxygenase-1 catalyzes the synthesis of 17S-H(p)DHA, which in turn is converted to a 16(17)-epoxide and then is enzymatically hydrolyzed to NPD1
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Fig4: The characterization and quantification of 17-HDHA and NPD1 in the ipsilateral penumbra 3 days after MCAo. a–b The fragmentation pattern is depicted and c the quantification is presented. The increased content of 17-HDHA and of NPD1 in the ipsilateral penumbra in animals injected with DHA is consistent with the activation of the biosynthesis of NPD1. d Enzyme-mediated oxygenation of DHA for the biosynthesis of NPD1. Phospholipase A2 releases DHA from the second C position of phospholipids during brain ischemia-reperfusion. 15-Lipoxygenase-1 catalyzes the synthesis of 17S-H(p)DHA, which in turn is converted to a 16(17)-epoxide and then is enzymatically hydrolyzed to NPD1

Mentions: Because DHA is the precursor of NPD1 [11], we asked if NPD1 synthesis occurs in the penumbra. Figure 4a–c shows that DHA treatment potentiates NPD1 synthesis in the penumbra 3 days after MCAo. We ascertained NPD1 synthesis in the penumbra by isolating and characterizing 17-HDHA. 17-HDHA reflects the presence of the unstable 17S-HpDHA. Since 17-HDHA and NPD1 were enhanced in the penumbra by DHA, we concluded that active NPD1 synthesis occurs under these conditions. Figure 4d illustrates the release of DHA from the membrane followed by the biosynthesis of NPD1.Fig. 4


Docosahexaenoic Acid therapy of experimental ischemic stroke.

Belayev L, Khoutorova L, Atkins KD, Eady TN, Hong S, Lu Y, Obenaus A, Bazan NG - Transl Stroke Res (2010)

The characterization and quantification of 17-HDHA and NPD1 in the ipsilateral penumbra 3 days after MCAo. a–b The fragmentation pattern is depicted and c the quantification is presented. The increased content of 17-HDHA and of NPD1 in the ipsilateral penumbra in animals injected with DHA is consistent with the activation of the biosynthesis of NPD1. d Enzyme-mediated oxygenation of DHA for the biosynthesis of NPD1. Phospholipase A2 releases DHA from the second C position of phospholipids during brain ischemia-reperfusion. 15-Lipoxygenase-1 catalyzes the synthesis of 17S-H(p)DHA, which in turn is converted to a 16(17)-epoxide and then is enzymatically hydrolyzed to NPD1
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3037476&req=5

Fig4: The characterization and quantification of 17-HDHA and NPD1 in the ipsilateral penumbra 3 days after MCAo. a–b The fragmentation pattern is depicted and c the quantification is presented. The increased content of 17-HDHA and of NPD1 in the ipsilateral penumbra in animals injected with DHA is consistent with the activation of the biosynthesis of NPD1. d Enzyme-mediated oxygenation of DHA for the biosynthesis of NPD1. Phospholipase A2 releases DHA from the second C position of phospholipids during brain ischemia-reperfusion. 15-Lipoxygenase-1 catalyzes the synthesis of 17S-H(p)DHA, which in turn is converted to a 16(17)-epoxide and then is enzymatically hydrolyzed to NPD1
Mentions: Because DHA is the precursor of NPD1 [11], we asked if NPD1 synthesis occurs in the penumbra. Figure 4a–c shows that DHA treatment potentiates NPD1 synthesis in the penumbra 3 days after MCAo. We ascertained NPD1 synthesis in the penumbra by isolating and characterizing 17-HDHA. 17-HDHA reflects the presence of the unstable 17S-HpDHA. Since 17-HDHA and NPD1 were enhanced in the penumbra by DHA, we concluded that active NPD1 synthesis occurs under these conditions. Figure 4d illustrates the release of DHA from the membrane followed by the biosynthesis of NPD1.Fig. 4

Bottom Line: Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h.Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points.Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo.

View Article: PubMed Central - PubMed

ABSTRACT
We examined the neuroprotective efficacy of docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, in acute ischemic stroke; studied the therapeutic window; and investigated whether DHA administration after an ischemic stroke is able to salvage the penumbra. In each series described below, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo). In series 1, DHA or saline was administered i.v. at 3, 4, 5, or 6 h after stroke. In series 2, MRI was conducted on days 1, 3 and 7. In series 3, DHA or saline was administered at 3 h, and lipidomic analysis was conducted on day 3. Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h. Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points. Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo. DHA administration provides neurobehavioral recovery, reduces brain infarction and edema, and activates NPD1 synthesis in the penumbra when administered up to 5 h after focal cerebral ischemia in rats.

No MeSH data available.


Related in: MedlinePlus