| 1. |
- Li, Kenan, et al.
(author)
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Sex differences in neonatal mouse brain injury after hypoxia-ischemia and adaptaquin treatment
- 2019
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 150:6, s. 759-775
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Journal article (peer-reviewed)abstract
- Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-PHDs) are important targets against oxidative stress. We hypothesized that inhibition HIF-PHD by adaptaquin reduces hypoxic-ischemic brain injury in a neonatal mouse model. The pups were treated intraperitoneally immediately with adaptaquin after hypoxia-ischemia (HI) and then every 24 h for 3 days. Adaptaquin treatment reduced infarction volume by an average of 26.3% at 72 h after HI compared to vehicle alone, and this reduction was more pronounced in males (34.8%) than in females (11.7%). The protection was also more pronounced in the cortex. The subcortical white matter injury as measured by tissue loss volume was reduced by 24.4% in the adaptaquin treatment group, and this reduction was also more pronounced in males (28.4%) than in females (18.9%). Cell death was decreased in the cortex as indicated by Fluoro-Jade labeling, but not in other brain regions with adaptaquin treatment. Furthermore, in the brain injury area, adaptaquin did not alter the number of cells positive for caspase-3 activation or translocation of apoptosis-inducing factor to the nuclei. Adaptaquin treatment increased glutathione peroxidase 4 mRNA expression in the cortex but had no impact on 3-nitrotyrosine, 8-hydroxy-2 deoxyguanosine, or malondialdehyde production. Hif1 alpha mRNA expression increased after HI, and adaptaquin treatment also stimulated Hif1 alpha mRNA expression, which was also more pronounced in males than in females. However, nuclear translocation of HIF1 alpha protein was decreased after HI, and adaptaquin treatment had no influence on HIF1 alpha expression in the nucleus. These findings demonstrate that adaptaquin treatment is neuroprotective, but the potential mechanisms need further investigation. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at .
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| 2. |
- Wang, Yafeng, 1985, et al.
(author)
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Selective Neural Deletion of the Atg7 Gene Reduces Irradiation-Induced Cerebellar White Matter Injury in the Juvenile Mouse Brain by Ameliorating Oligodendrocyte Progenitor Cell Loss
- 2019
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In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Journal article (peer-reviewed)abstract
- Radiotherapy is an effective tool for treating brain tumors, but irradiation-induced toxicity to the normal brain tissue remains a major problem. Here, we investigated if selective neural autophagy related gene 7 (Atg7) deletion has a persistent effect on irradiation-induced juvenile mouse brain injury. Ten-day-old Atg7 knockout under a nestin promoter (KO) mice and wild-type (WT) littermates were subjected to a single dose of 6 Gy whole-brain irradiation. Cerebellar volume, cell proliferation, microglia activation, inflammation, and myelination were evaluated in the cerebellum at 5 days after irradiation. We found that neural Atg7 deficiency partially prevented myelin disruption compared to the WT mice after irradiation, as indicated by myelin basic protein staining. Irradiation induced oligodendrocyte progenitor cell (OPC) loss in the white matter of the cerebellum, and Atg7 deficiency partly prevented this. The mRNA expression of oligodendrocyte and myelination-related genes (Olig2, Cldn11, CNP, and MBP) was higher in the cerebellum in Atg7 KO mice compared with WT littermates. The total cerebellar volume was significantly reduced after irradiation in both Atg7 KO and WT mice. Atg7-deficient cerebellums were in a regenerative state before irradiation, as judged by the increased OPC-related and neurogenesis-related transcripts and the increased numbers of microglia; however, except for the OPC parameters these were the same in both genotypes after irradiation. Finally, there was no significant change in the number of astrocytes in the cerebellum after irradiation. These results suggest that selective neural Atg7 deficiency reduces irradiation-induced cerebellar white matter injury in the juvenile mouse brain, secondary to prevention of OPC loss.
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| 3. |
- Yuan, Justin P., et al.
(author)
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Test-retest reliability of graph theoretic metrics in adolescent brains
- 2019
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In: Brain Connectivity. - : Mary Ann Liebert. - 2158-0014 .- 2158-0022. ; 9:2, s. 144-154
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Journal article (peer-reviewed)abstract
- Graph theory analysis of structural brain networks derived from diffusion tensor imaging (DTI) has become a popular analytical method in neuroscience, enabling advanced investigations of neurological and psychiatric disorders. The purpose of this study was to investigate: 1) the effects of edge weighting schemes, and 2) the effects of varying interscan periods on graph metrics' test-retest reliability within the adolescent brain. We compared a binary (B) network definition with three weighting schemes: fractional anisotropy (FA), streamline count (SC), and streamline count with density and length correction (SDL). Two commonly used global and two local graph metrics were examined. The analysis was conducted with two groups of adolescent volunteers who received DTI scans either 12 weeks apart (16.62±1.10yrs) or within the same scanning session (30 minutes apart) (16.65±1.14yrs). The intraclass correlation coefficient (ICC) was used to assess test-retest reliability and the coefficient of variation (CV) was used to assess precision. On average, each edge scheme produced reliable results at both time intervals. Weighted measures outperformed binary measures, with SDL-weights producing the most reliable metrics. All edge schemes except FA displayed high CV values, leaving FA as the only edge scheme that consistently showed high precision while also producing reliable results. Overall findings suggest that FA-weights are more suited for DTI connectome studies in adolescents.
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