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Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.

ABSTRACT: Current available therapies for neonatal hypoxia/ischemia (H/I) brain injury are rather limited. Here, we investigated the effect of omega-3 polyunsaturated fatty acids on brain damage and long-term neurological function after H/I in neonates.Female rats were treated with or without an omega-3 polyunsaturated fatty acids-enriched diet from the second day of pregnancy until 14 days after parturition. Seven-day-old neonates were subjected to H/I and euthanized 5 weeks later for evaluation of tissue loss. Neurological impairment was assessed progressively for 5 weeks after H/I by grid walking, foot fault, and Morris water maze. Activation of microglia and production of inflammatory mediators were examined up to 7 days after H/I.Omega-3 polyunsaturated fatty acid supplementation significantly reduced brain damage and improved long-term neurological outcomes up to 5 weeks after neonatal H/I injury. Omega-3 polyunsaturated fatty acids exerted an anti-inflammatory effect in microglia both in an in vivo model of H/I and in in vitro microglial cultures subjected to inflammatory stimuli by inhibiting NF-?B activation and subsequent release of inflammatory mediators.Our results suggest that omega-3 polyunsaturated fatty acids confer potent neuroprotection against neonatal H/I brain injury through, at least partially, suppressing a microglial-mediated inflammatory response.

SUBMITTER: Zhang W

PROVIDER: S-EPMC3021248 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.

Zhang Wenting W Hu Xiaoming X Yang Wei W Gao Yanqin Y Chen Jun J

Stroke 20100812 10

<h4>Background and purpose</h4>Current available therapies for neonatal hypoxia/ischemia (H/I) brain injury are rather limited. Here, we investigated the effect of omega-3 polyunsaturated fatty acids on brain damage and long-term neurological function after H/I in neonates.<h4>Methods</h4>Female rats were treated with or without an omega-3 polyunsaturated fatty acids-enriched diet from the second day of pregnancy until 14 days after parturition. Seven-day-old neonates were subjected to H/I and e ...[more]

PMID: 20705927

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Project description:Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the "single cortical microinfarct model" generated via occluding a penetrating arteriole by femtosecond laser ablation and the "multiple diffuse microinfarcts model" induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (?-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ?-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ?-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ?-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ?-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ?-3 PUFAs in the treatment or prophylaxis in vascular dementia.

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Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.

Publications

Omega-3 polyunsaturated fatty acid supplementation confers long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions.

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