Abstract
Ischemic stroke is one of the leading causes of death and disability for adults, which lacks effective treatments. Dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) exerts beneficial effects on ischemic stroke by attenuating neuron death and inflammation induced by microglial activation. However, the impact and mechanism of n-3 PUFAs on astrocyte function during stroke have not yet been well investigated. Our current study found that dietary n-3 PUFAs decreased the infarction volume and improved the neurofunction in the mice model of transient middle cerebral artery occlusion (tMCAO). Notably, n-3 PUFAs reduced the stroke-induced A1 astrocyte polarization both in vivo and in vitro. We have demonstrated that exogenous n-3 PUFAs attenuated mitochondrial oxidative stress and increased the mitophagy of astrocytes in the condition of hypoxia. Furthermore, we provided evidence that treatment with the mitochondrial-derived antioxidant, mito-TEMPO, abrogated the n-3 PUFA-mediated regulation of A1 astrocyte polarization upon hypoxia treatment. Together, this study highlighted that n-3 PUFAs prevent mitochondrial dysfunction, thereby limiting A1-specific astrocyte polarization and subsequently improving the neurological outcomes of mice with ischemic stroke.
Highlights
Ischemic stroke is caused by interruption of the blood supply to a part of the brain leading to the sudden loss of function, which now is one of the leading causes of death and disability worldwide [1]
Our results showed that n-3 PUFA feeding improved stroke outcomes during the acute phase of cerebral ischemia associated with astrocyte plasticity
In order to estimate whether dietary n-3 PUFAs reduce infarction and improve neurofunctional recovery after transient middle cerebral artery occlusion (tMCAO), we used TTC staining, neurobehavioral test, and neurological scores to assess brain injury in mice
Summary
Ischemic stroke is caused by interruption of the blood supply to a part of the brain leading to the sudden loss of function, which now is one of the leading causes of death and disability worldwide [1]. An increasing number of studies indicate that in the acute phase of ischemic stroke, astrocytes limit brain damage by activation and glial scar formation [2], modulate neuroinflammation by releasing cytokines [3], reconstruct the blood-brain barrier by reestablishment of the astrocytic water channels [4], and affect the neuron survival by metabolic substrates [5, 6] and signalling molecule transfer [7]. In addition to such functional diversity, the transcripts of reactive astrocytes are different. Dietary n-3 PUFA supplement upregulated the transcripts of A1-specific astrocytes, which is related to mitochondrial damage-related oxidative stress
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