High-Dose Vitamin C Prevents Secondary Brain Damage After Stroke via Epigenetic Reprogramming of Neuroprotective Genes.
High-Dose Vitamin C Prevents Secondary Brain Damage After Stroke via Epigenetic Reprogramming of Neuroprotective Genes.
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高剂量维生素C可通过神经保护基因的表观遗传重编程进行中风后的继发性脑损伤。
DOI：
10.1007/s12975-022-01007-6
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发表时间：
2022-12
影响因子：
6.9
通讯作者：
Vemuganti, Raghu
中科院分区：
文献类型：
--
作者：
Morris-Blanco, Kahlilia C.;Chokkalla, Anil K.;Kim, TaeHee;Bhatula, Saivenkateshkomal;Bertogliat, Mario J.;Gaillard, Alexis B.;Vemuganti, Raghu
Vitamin C has recently been identified as an epigenetic regulator by activating ten eleven translocases (TETs), enzymes involved in generating DNA hydroxymethylcytosine (5hmC). Currently we investigated whether high dose Vitamin C promotes neuroprotection through epigenetic modulation of 5hmC, if there are sex-specific differences in outcome, and the therapeutic potential of ascorbate in stroke-related comorbidities in adult mice. Post-stroke treatment with ascorbate (reduced form), but not dehydroascorbate (oxidized form), increased TET3 activity, 5hmC levels and reduced infarct following focal ischemia. Hydroxymethylation DNA immunoprecipitation-sequencing showed that ascorbate increased 5hmC across the genome and specifically in promoters of several stroke pathophysiology-related genes, particularly anti-inflammatory genes. Ascorbate also decreased markers of oxidative stress, mitochondrial fragmentation and apoptosis in cortical peri-infarct neurons and promoted motor and cognitive functional recovery in both sexes via TET3. Furthermore, post-stroke ascorbate treatment reduced infarct volume and improved motor function recovery in aged, hypertensive and diabetic male and female mice. Delayed ascorbate treatment at 6h of reperfusion was still effective at reducing infarct volume and motor impairments in adult mice. Collectively, this study shows that post-stroke treatment with high dose ascorbate protects the brain through epigenetic reprogramming and may function as a robust therapeutic against stroke injury.
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影响因子：
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