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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

Therapeutic window study: a Neurological score (normal score = 0; maximum score = 12) was improved after DHA administration when administered 3, 4, and 5 h after onset of stroke. Cortical (b), subcortical (c), and total corrected infarct volumes (d) on day 7. DHA reduced cortical and total infarct volumes when administered 3, 4, and 5 h after stroke. Data are means ± SEM. Asterisk, significantly different from saline (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). e Computer-generated MosaiX-processed images of Nissl stained paraffin-embedded brain sections from rats treated with saline or DHA at 3, 4, 5, and 6 h after the onset of ischemia. Saline-treated rat shows large cortical and subcortical infarction. In contrast, rats treated with DHA at 3, 4, and 5 h show less extensive damage, mostly in the subcortical area. DHA-treated rat at 6 h shows infarct involving cortical and subcortical regions. f Computer-generated MosaiX-processed images of GFAP (green), ED-1 (red), and GFAP/ED-1 double staining (overlay) on day 7 after 2 h of MCAo at a magnification ×10. Treatment with DHA or saline was given at 3 h after onset of stroke
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Fig1: Therapeutic window study: a Neurological score (normal score = 0; maximum score = 12) was improved after DHA administration when administered 3, 4, and 5 h after onset of stroke. Cortical (b), subcortical (c), and total corrected infarct volumes (d) on day 7. DHA reduced cortical and total infarct volumes when administered 3, 4, and 5 h after stroke. Data are means ± SEM. Asterisk, significantly different from saline (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). e Computer-generated MosaiX-processed images of Nissl stained paraffin-embedded brain sections from rats treated with saline or DHA at 3, 4, 5, and 6 h after the onset of ischemia. Saline-treated rat shows large cortical and subcortical infarction. In contrast, rats treated with DHA at 3, 4, and 5 h show less extensive damage, mostly in the subcortical area. DHA-treated rat at 6 h shows infarct involving cortical and subcortical regions. f Computer-generated MosaiX-processed images of GFAP (green), ED-1 (red), and GFAP/ED-1 double staining (overlay) on day 7 after 2 h of MCAo at a magnification ×10. Treatment with DHA or saline was given at 3 h after onset of stroke

Mentions: Neurological deficits were reduced by DHA, even when treatment was initiated as late as 5 h after MCAo onset (Fig. 1a): day 1 (DHA: 3 h, 7.7 ± 0.2; 4 h, 6.9 ± 0.7; 5 h, 7.2 ± 0.5; and 6 h, 8.3 ± 0.2 vs. Saline: 9.8 ± 0.2; p < 0.01), day 2 (DHA: 3 h, 7.7 ± 0.2; 5 h, 6.5 ± 0.8; and 6 h, 7.8 ± 0.3 vs. Saline: 9.8 ± 0.2; p < 0.01), day 3 (DHA: 3 h, 7.1 ± 0.6; 5 h, 6.0 ± 1.0; and 6 h, 8.2 ± 0.4 vs. Saline: 9.7 ± 0.2; p < 0.003) and day 7 (DHA: 3 h, 6.0 ± 0.6; 4 h, 5.7 ± 1.0; 5 h, 5.5 ± 0.9 vs. Saline: 9.0 ± 0.3; p < 0.0004). DHA-mediated protection was extensive in the frontal–parietal cortex (tissue salvage, 49% (p < 0.02), 77% (p < 0.002), and 71% (p < 0.004), respectively for 3 h, 4 h and 5 h; Fig. 1b) and across multiple coronal levels. DHA administration did not affect the subcortical infarct, except when it was infused at 4 h (p < 0.01; Fig. 1c). Total infarct volume, corrected for brain swelling, was reduced by 40% (p < 0.02) when DHA was administered at 3 h, by 66% (p < 0.001) at 4 h, and by 59% (p < 0.003) at 5 h (Fig. 1d). The brains of saline-treated rats exhibited a consistent pannecrotic lesion involving both cortical and subcortical (mainly striatal) regions of the right hemisphere, characterized microscopically by destruction of neuronal, glial, and vascular elements. In contrast, infarct size was dramatically reduced in rats treated with DHA at 3, 4, and 5 h after onset of ischemia, but not in 6-h group (Fig. 1e).Fig. 1


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)

Therapeutic window study: a Neurological score (normal score = 0; maximum score = 12) was improved after DHA administration when administered 3, 4, and 5 h after onset of stroke. Cortical (b), subcortical (c), and total corrected infarct volumes (d) on day 7. DHA reduced cortical and total infarct volumes when administered 3, 4, and 5 h after stroke. Data are means ± SEM. Asterisk, significantly different from saline (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). e Computer-generated MosaiX-processed images of Nissl stained paraffin-embedded brain sections from rats treated with saline or DHA at 3, 4, 5, and 6 h after the onset of ischemia. Saline-treated rat shows large cortical and subcortical infarction. In contrast, rats treated with DHA at 3, 4, and 5 h show less extensive damage, mostly in the subcortical area. DHA-treated rat at 6 h shows infarct involving cortical and subcortical regions. f Computer-generated MosaiX-processed images of GFAP (green), ED-1 (red), and GFAP/ED-1 double staining (overlay) on day 7 after 2 h of MCAo at a magnification ×10. Treatment with DHA or saline was given at 3 h after onset of stroke
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Fig1: Therapeutic window study: a Neurological score (normal score = 0; maximum score = 12) was improved after DHA administration when administered 3, 4, and 5 h after onset of stroke. Cortical (b), subcortical (c), and total corrected infarct volumes (d) on day 7. DHA reduced cortical and total infarct volumes when administered 3, 4, and 5 h after stroke. Data are means ± SEM. Asterisk, significantly different from saline (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). e Computer-generated MosaiX-processed images of Nissl stained paraffin-embedded brain sections from rats treated with saline or DHA at 3, 4, 5, and 6 h after the onset of ischemia. Saline-treated rat shows large cortical and subcortical infarction. In contrast, rats treated with DHA at 3, 4, and 5 h show less extensive damage, mostly in the subcortical area. DHA-treated rat at 6 h shows infarct involving cortical and subcortical regions. f Computer-generated MosaiX-processed images of GFAP (green), ED-1 (red), and GFAP/ED-1 double staining (overlay) on day 7 after 2 h of MCAo at a magnification ×10. Treatment with DHA or saline was given at 3 h after onset of stroke
Mentions: Neurological deficits were reduced by DHA, even when treatment was initiated as late as 5 h after MCAo onset (Fig. 1a): day 1 (DHA: 3 h, 7.7 ± 0.2; 4 h, 6.9 ± 0.7; 5 h, 7.2 ± 0.5; and 6 h, 8.3 ± 0.2 vs. Saline: 9.8 ± 0.2; p < 0.01), day 2 (DHA: 3 h, 7.7 ± 0.2; 5 h, 6.5 ± 0.8; and 6 h, 7.8 ± 0.3 vs. Saline: 9.8 ± 0.2; p < 0.01), day 3 (DHA: 3 h, 7.1 ± 0.6; 5 h, 6.0 ± 1.0; and 6 h, 8.2 ± 0.4 vs. Saline: 9.7 ± 0.2; p < 0.003) and day 7 (DHA: 3 h, 6.0 ± 0.6; 4 h, 5.7 ± 1.0; 5 h, 5.5 ± 0.9 vs. Saline: 9.0 ± 0.3; p < 0.0004). DHA-mediated protection was extensive in the frontal–parietal cortex (tissue salvage, 49% (p < 0.02), 77% (p < 0.002), and 71% (p < 0.004), respectively for 3 h, 4 h and 5 h; Fig. 1b) and across multiple coronal levels. DHA administration did not affect the subcortical infarct, except when it was infused at 4 h (p < 0.01; Fig. 1c). Total infarct volume, corrected for brain swelling, was reduced by 40% (p < 0.02) when DHA was administered at 3 h, by 66% (p < 0.001) at 4 h, and by 59% (p < 0.003) at 5 h (Fig. 1d). The brains of saline-treated rats exhibited a consistent pannecrotic lesion involving both cortical and subcortical (mainly striatal) regions of the right hemisphere, characterized microscopically by destruction of neuronal, glial, and vascular elements. In contrast, infarct size was dramatically reduced in rats treated with DHA at 3, 4, and 5 h after onset of ischemia, but not in 6-h group (Fig. 1e).Fig. 1

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