Abstract | OBJECTIVE: MATERIALS AND METHODS: Sprague-Dawley rats received 2 h MCAo and LAU-0901 (30 or 60 mg/kg, 2 h after stroke), NPD1, and AT-NPD1 (333 μg/kg), DHA (5 mg/kg), and their combination were administered intravenous at 3 h after stroke. Behavior testing and ex vivo magnetic resonance imaging were conducted on day 3 or 14 to assess lesion characteristics and lipidomic analysis on day 1. Series 1 ( LAU-0901 + NPD1, 14d), Series 2 ( LAU-0901 + AT-NPD1, 3d), and Series 3 ( LAU-0901 + DHA, 1d). RESULTS: All combinatory groups improved behavior compared to NPD1, AT-NPD1, or DHA treatments alone. Total lesion volumes were reduced with LAU-0901 + NPD1 by 62% and LAU-0901 + AT-NPD1 by 90% treatments versus vehicle groups. LAU-0901 and LAU-0901 + DHA increased the production of vasoactive lipid mediators ( prostaglandins: PGE2, PGF2- α, 6-keto- PGF1- α, and PGD2) as well an inflammatory regulating mediator hydroxyoctadecadienoic acid. In contrast, LAU-0901 and LAU-0901 + DHA decreased the production of 12-hydroxyeicosatetraenoic acid, a pro-inflammatory mediator. CONCLUSION: Combination therapy with LAU-0901 and selected docosanoids is more effective than the single therapy, affording synergistic neuroprotection, with restored pro-homeostatic lipid mediators and improved neurological recovery. Altogether, our findings support the combinatory therapy as the basis for future therapeutics for ischemic stroke.
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Authors | Ludmila Belayev, Andre Obenaus, Pranab K Mukherjee, Eric J Knott, Larissa Khoutorova, Madigan M Reid, Cassia R Roque, Lawrence Nguyen, Jeong Bin Lee, Nicos A Petasis, Reinaldo B Oria, Nicolas G Bazan |
Journal | Brain circulation
(Brain Circ)
2020 Oct-Dec
Vol. 6
Issue 4
Pg. 260-268
ISSN: 2455-4626 [Electronic] India |
PMID | 33506149
(Publication Type: Journal Article)
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Copyright | Copyright: © 2020 Brain Circulation. |