Abstract TP106: N-3 Polyunsaturated Fatty Acid Enhances Neurovascular Remodeling After Acute Cerebral Ischemia
INTRODUCTION: Ischemic stroke triggers multiple repair responses, including neurogenesis, angiogenesis and oligodendrogenesis. These endogenous processes, however, are insufficient for effective brain repair. Our previous study has shown that omega-3 polyunsaturated fatty acid (N3 PUFA) is a potential neurogenic treatment for stroke recovery. The effect of N3 PUFA on revasularization and white matter recovery, however, remains unexplored.
HYPOTHESIS: N3 PUFA enhances revasularization and white matter recovery after ischemic stroke, leading to long-term neurological recovery.
METHODS: Mice were treated with N3 PUFA-enriched diet or regular diet for 3 months and then subjected to MCAO for 60 minutes. Brdu was administered to label newly generated cells. Animals were sacrificed on day 1, 3, 7, 14 or 35 of reperfusion. Functional vessels were identified by transcardial perfusion of FITC-conjugated tomato lectin, which labels endothelial cells only in perfused vessels. White matter integrity was evaluated by immunohistochemistry staining of myelin basic protein (MBP), SMI32 and neurofilament (NF) 200.
RESULTS: The vascular reperfusion in the ischemic core and penumbra was preserved in N3 PUFA-supplemented mice since 1 day after MCAO and maintained significantly higher than regular diet group up to 35 days post-injury. Angiogenesis was enhanced by N3 PUFA, as revealed by substantially increased double staining of Brdu with tomato lectin at 7-35 days after MCAO. Importantly, clusters of DCX+ immature neurons localized proximal to revascularized vessels beginning 14 days after ischemia, suggesting interplay between revascularization and neurogenesis. Post-stroke white matter injury was also ameliorated by N3 PUFA, as revealed by enhanced MBP staining for mature myelin and reduced SMI32 staining for abnormally dephosphorylated neurofilament. Meanwhile, axon integrity was markedly preserved in N3 PUFA-treated mice. As a result, N3 PUFA supplementation significantly reduced the infarct volume, which was accompanied by improved neurological functions up to 35 days after reperfusion.
- © 2012 by American Heart Association, Inc.