Valproic acid increases white matter repair and neurogenesis after stroke
| Autor: | Michael Chopp, Yi Sheng Cui, Rui Lan Zhang, Long Fei Jia, Zheng Gang Zhang, Haifa Kassis, Xian Shuang Liu, Ann Hozeska-Solgot, Charles Chen |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Neurogenesis medicine.medical_treatment Biology Nerve Fibers Myelinated Article White matter Internal medicine In Situ Nick-End Labeling medicine Animals Stroke Valproic Acid General Neuroscience Brain Recovery of Function medicine.disease Immunohistochemistry Neural stem cell Oligodendrocyte Rats Histone Deacetylase Inhibitors Endocrinology medicine.anatomical_structure lipids (amino acids peptides and proteins) Histone deacetylase Stroke recovery Neuroscience medicine.drug |
| Zdroj: | Neuroscience. 220:313-321 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2012.06.012 |
| Popis: | Acute treatment of stroke with histone deacetylase (HDAC) inhibitors has been shown to reduce ischemic cell damage; however, it is unclear whether delayed treatment with HDAC inhibitors will contribute to the brain repair and plasticity. In the present study, we investigated the effects of delayed treatment of stroke with a pan HDAC inhibitor, valproic acid (VPA), on white matter injury and neurogenesis during stroke recovery. Administration of VPA at a dose of 100mg/kg for 7 days starting 24h after middle cerebral artery occlusion (MCAo) in rats significantly improved neurological outcome measured 7-28 days post-MCAo. In addition, the VPA treatment significantly increased oligodendrocyte survival and newly generated oligodendrocytes, which was associated with elevation of myelinated axonal density in the ischemic boundary 28 days after MCAo. VPA treatment also increased the expression of glutamate transporter 1 (GLT1) in the ischemic boundary after stroke, and increased acetylated histone H4 expression in neuroblasts and the number of new neurons in striatal ischemic boundary region. This study provides new evidence that the delayed VPA treatment enhances white matter repair and neurogenesis in ischemic brain, which may contribute to improved functional outcome. |
| Databáze: | OpenAIRE |
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