Academic Journal
Thiol-Based Neuroprotective Copolymers Acutely Restore Redox Metabolism and Mediate Vasogenic Edema in a Mouse Model of Traumatic Brain Injury.
| Τίτλος: | Thiol-Based Neuroprotective Copolymers Acutely Restore Redox Metabolism and Mediate Vasogenic Edema in a Mouse Model of Traumatic Brain Injury. |
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| Συγγραφείς: | Curtis ET; Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., McDonald BZ; Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Tarudji AW; Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Priester AM; Department of Material Science and Engineering, Missouri University of Science and Technology, Rolla, Missouri, USA., Convertine AJ; Department of Material Science and Engineering, Missouri University of Science and Technology, Rolla, Missouri, USA., Kievit FM; Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. |
| Πηγή: | Macromolecular bioscience [Macromol Biosci] 2026 Jul; Vol. 26 (7), pp. e00642. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101135941 Publication Model: Print Cited Medium: Internet ISSN: 1616-5195 (Electronic) Linking ISSN: 16165187 NLM ISO Abbreviation: Macromol Biosci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim, Germany : Wiley-VCH, c2001- |
| Ιατρικοί όροι (MeSH): | Brain Injuries, Traumatic*/drug therapy , Brain Injuries, Traumatic*/metabolism , Brain Injuries, Traumatic*/pathology , Brain Injuries, Traumatic*/complications , Brain Injuries, Traumatic*/diagnostic imaging , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/chemistry , Polymers*/pharmacology , Polymers*/chemistry , Sulfhydryl Compounds*/chemistry , Sulfhydryl Compounds*/pharmacology , Brain Edema*/drug therapy , Brain Edema*/metabolism , Brain Edema*/pathology, Oxidation-Reduction/drug effects ; Nanoparticles/chemistry ; Reactive Oxygen Species/metabolism ; Antioxidants/pharmacology ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/drug effects ; Lipid Peroxidation/drug effects ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/drug effects ; Glial Fibrillary Acidic Protein/metabolism ; Animals ; Mice ; Disease Models, Animal ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Effective pharmaceutical interventions for treating the secondary damage associated with traumatic brain injury (TBI) are limited due to poor delivery into the brain, insufficient target engagement, and an incomplete understanding of the pathophysiological changes that occur post-impact. Thus, nanoparticles (NP), which have an enhanced permeation and retention-like effect within the perturbed blood-brain barrier, have grown as a potential candidate for treating TBI. We have investigated the antioxidant capacity of thiol-based NP, termed neuroprotective copolymers (NPC3), and their ability to neutralize reactive oxygen species (ROS) and lipid peroxidation products (LPOx). Here, we assessed the efficacy of NPC3 for alleviating the secondary injury cascade in TBI with a specific focus on ameliorating molecular and structural deficits in a mouse controlled cortical impact (CCI) model. NPC3 delivered post-CCI alleviated oxidant burden, reducing both antioxidant enzyme expression and Nrf2 activation. These changes in redox signaling resulted in a shift in metabolic function, with increased AMPK activation with NPC3 treatment. T2-weighted and diffusion magnetic resonance imaging revealed vasogenic edema formation at 30 days post-CCI and alterations in mean diffusivity, which were moderated by NPC3. Furthermore, NPC3 reduced GFAP and Iba1 at multiple impact severities, which positively correlated with urinary 8-isoprostane. Overall, this work shows NPC3 reduced glial reactivity, affected redox metabolism, and ultimately contributed to improvements in structural deficits post-CCI. (© 2026 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.) |
| References: | A. I. Maas, D. K. Menon, G. T. Manley, et al., “Traumatic Brain Injury: Progress and Challenges in Prevention, Clinical Care, and Research,” The Lancet Neurology 21, no. 11 (2022): 1004–1060. M. C. Dewan, A. Rattani, S. Gupta, et al., “Estimating the Global Incidence of Traumatic Brain Injury,” Journal of Neurosurgery 130, no. 4 (2019): 1080–1097, https://doi.org/10.3171/2017.10.JNS17352. A. C. McKee, T. D. Stein, B. R. Huber, et al., “Chronic Traumatic Encephalopathy (CTE): Criteria for Neuropathological Diagnosis and Relationship to Repetitive Head Impacts,” Acta Neuropathologica 145, no. 4 (2023): 371–394, https://doi.org/10.1007/s00401‐023‐02540‐w. Y. Mehkri, B. McDonald, S. Sriram, et al., “Recent Treatment Strategies in Alzheimer's Disease and Chronic Traumatic Encephalopathy,” Biomedical Research and Clinical Reviews 7, no. 3 (2022): 1–14, https://doi.org/10.31579/2692‐9406/128. V. Delic, K. D. Beck, K. C. Pang, and B. A. Citron, “Biological Links Between Traumatic Brain Injury and Parkinson's Disease,” Acta Neuropathologica Communications 8 (2020): 1–16, https://doi.org/10.1186/s40478‐020‐00924‐7. S. Fordington and M. Manford, “A Review of Seizures and Epilepsy Following Traumatic Brain Injury,” Journal of Neurology 267, no. 10 (2020): 3105–3111, https://doi.org/10.1007/s00415‐020‐09926‐w. S. Datta, F. Lin, L. D. Jones, S. C. Pingle, S. Kesari, and S. Ashili, “Traumatic Brain Injury and Immunological Outcomes: The Double‐edged Killer,” Future Science OA 9, no. 6 (2023): FSO864, https://doi.org/10.2144/fsoa‐2023‐0037. P. M. Kochanek, H. M. Bramlett, C. E. Dixon, et al., “Operation Brain Trauma Therapy: 2016 Update,” Mil Med 183, no. 1 (2018): 303–312. G. T. Manley, C. L. Mac Donald, A. J. Markowitz, et al., “T.E.D. Investigators, The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public‐Private Regulatory Collaboration To Accelerate Diagnosis and Treatment of Traumatic Brain Injury,” Journal of Neurotrauma 34, no. 19 (2017): 2721–2730, https://doi.org/10.1089/neu.2016.4729. E. A. Wilde, I. B. Wanner, K. Kenney, et al., “A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury,” Journal of Neurotrauma 39, no. 7‐8 (2022): 436–457, https://doi.org/10.1089/neu.2021.0099. D. W. Simon, M. J. McGeachy, H. Bayir, R. S. Clark, D. J. Loane, and P. M. Kochanek, “The Far‐Reaching Scope of Neuroinflammation After Traumatic Brain Injury,” Nature Reviews Neurology 13, no. 3 (2017): 171–191, https://doi.org/10.1038/nrneurol.2017.13. J. Zhuo, S. Xu, J. L. Proctor, et al., “Diffusion Kurtosis as an In Vivo Imaging Marker for Reactive Astrogliosis in Traumatic Brain Injury,” Neuroimage 59, no. 1 (2012): 467–477. V. N. Bharadwaj, D. T. Nguyen, V. D. Kodibagkar, and S. E. Stabenfeldt, “Nanoparticle‐Based Therapeutics for Brain Injury,” Advanced Healthcare Materials 7, no. 1 (2018): 1700668. V. N. Bharadwaj, J. Lifshitz, P. D. Adelson, V. D. Kodibagkar, and S. E. Stabenfeldt, “Temporal Assessment of Nanoparticle Accumulation After Experimental Brain Injury: Effect of Particle Size,” Scientific Reports 6, no. 1 (2016): 1–12, https://doi.org/10.1038/srep29988. B. Alam Bony and F. M. Kievit, “A Role for Nanoparticles in Treating Traumatic Brain Injury,” Pharmaceutics 11, no. 9 (2019): 473. H. A. Miller, A. W. Magsam, A. W. Tarudji, et al., “Evaluating Differential Nanoparticle Accumulation and Retention Kinetics in a Mouse Model of Traumatic Brain Injury via Ktrans Mapping With MRI,” Scientific Reports 9, no. 1 (2019): 1–14, https://doi.org/10.1038/s41598‐019‐52622‐7. J. Xu, M. Ypma, P. A. Chiarelli, et al., “Theranostic Oxygen Reactive Polymers for Treatment of Traumatic Brain Injury,” Advanced Functional Materials 26, no. 23 (2016): 4124–4133, https://doi.org/10.1002/adfm.201504416. D. Yoo, A. W. Magsam, A. M. Kelly, P. S. Stayton, F. M. Kievit, and A. J. Convertine, “Core‐Cross‐Linked Nanoparticles Reduce Neuroinflammation and Improve Outcome in a Mouse Model of Traumatic Brain Injury,” ACS Nano 11, no. 9 (2017): 8600–8611, https://doi.org/10.1021/acsnano.7b03426. A. W. Tarudji, C. C. Gee, S. M. Romereim, A. J. Convertine, and F. M. Kievit, “Antioxidant Thioether Core‐Crosslinked Nanoparticles Prevent the Bilateral Spread of Secondary Injury to Protect Spatial Learning and Memory in a Controlled Cortical Impact Mouse Model of Traumatic Brain Injury,” Biomaterials 272 (2021): 120766, https://doi.org/10.1016/j.biomaterials.2021.120766. A. W. Tarudji, H. A. Miller, E. T. Curtis, C. L. Porter, G. L. Madsen, and F. M. Kievit, “Sex‐Based Differences of Antioxidant Enzyme Nanoparticle Effects Following Traumatic Brain Injury,” Journal of Controlled Release 355 (2023): 149–159, https://doi.org/10.1016/j.jconrel.2023.01.065. A. Priester, R. Waters, A. Abbott, et al., “Theranostic Copolymers Neutralize Reactive Oxygen Species and Lipid Peroxidation Products for the Combined Treatment of Traumatic Brain Injury,” Biomacromolecules 23, no. 4 (2022): 1703–1712, https://doi.org/10.1021/acs.biomac.1c01635. A. W. Tarudji, C. C. Gee, H. A. Miller, et al., “Antioxidant Theranostic Copolymer‐Mediated Reduction in Oxidative Stress Following Traumatic Brain Injury Improves Outcome in a Mouse Model,” Advanced Therapeutics 6 (2023): 2300147, https://doi.org/10.1002/adtp.202300147. C. K. Riener, G. Kada, and H. J. Gruber, “Quick Measurement of Protein Sulfhydryls With Ellman's Reagent and With 4,4′‐Dithiodipyridine,” Analytical and Bioanalytical Chemistry 373, no. 4‐5 (2002): 266–276, https://doi.org/10.1007/s00216‐002‐1347‐2. B. Z. McDonald, A. W. Tarudji, H. Zhang, S. Ryu, K. M. Eskridge, and F. M. Kievit, “Traumatic Brain Injury Heterogeneity Affects Cell Death and Autophagy,” Experimental Brain Research 242, no. 7 (2024): 1645–1658, https://doi.org/10.1007/s00221‐024‐06856‐1. R. Di Sapia, F. Moro, M. Montanarella, et al., “In‐Depth Characterization of a Mouse Model of Post‐Traumatic Epilepsy for Biomarker and Drug Discovery,” Acta Neuropathologica Communications 9, no. 1 (2021): 76. M. V. Sofroniew and H. V. Vinters, “Astrocytes: Biology and Pathology,” Acta Neuropathol 119, no. 1 (2010): 7–35. J. E. Burda, A. M. Bernstein, and M. V. Sofroniew, “Astrocyte Roles in Traumatic Brain Injury,” Experimental Neurology 275 (2016): 305–315, https://doi.org/10.1016/j.expneurol.2015.03.020. A. Nandi, L.‐J. Yan, C. K. Jana, and N. Das, “Role of Catalase in Oxidative Stress‐and Age‐Associated Degenerative Diseases,” Oxidative Medicine and Cellular Longevity 2019 (2019): 9613090. A. Perkins, K. J. Nelson, D. Parsonage, L. B. Poole, and P. A. Karplus, “Peroxiredoxins: Guardians Against Oxidative Stress and Modulators of Peroxide Signaling,” Trends in Biochemical Sciences 40, no. 8 (2015): 435–445, https://doi.org/10.1016/j.tibs.2015.05.001. E. Lubos, J. Loscalzo, and D. E. Handy, “Glutathione Peroxidase‐1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities,” Antioxidants & Redox Signaling 15, no. 7 (2011): 1957–1997, https://doi.org/10.1089/ars.2010.3586. E. D. Hall, R. A. Vaishnav, and A. G. Mustafa, “Antioxidant Therapies for Traumatic Brain Injury,” Neurotherapeutics 7 (2010): 51–61, https://doi.org/10.1016/j.nurt.2009.10.021. J. E. Pankiewicz, J. R. Diaz, M. Martá‐Ariza, A. M. Lizińczyk, L. A. Franco, and M. J. Sadowski, “Peroxiredoxin 6 Mediates Protective Function of Astrocytes in Aβ Proteostasis,” Molecular Neurodegeneration 15 (2020): 1–22, https://doi.org/10.1186/s13024‐020‐00401‐8. J. Goemaere and B. Knoops, “Peroxiredoxin Distribution in the Mouse Brain With Emphasis on Neuronal Populations Affected in Neurodegenerative Disorders,” Journal of Comparative Neurology 520, no. 2 (2012): 258–280, https://doi.org/10.1002/cne.22689. L. Baird and M. Yamamoto, “The Molecular Mechanisms Regulating the KEAP1‐NRF2 Pathway,” Molecular and Cellular Biology 40, no. 13 (2020): e00099‐20, https://doi.org/10.1128/MCB.00099‐20. A. Loboda, M. Damulewicz, E. Pyza, A. Jozkowicz, and J. Dulak, “Role of Nrf2/HO‐1 System in Development, Oxidative Stress Response and Diseases: An Evolutionarily Conserved Mechanism,” Cellular and Molecular Life Sciences 73 (2016): 3221–3247, https://doi.org/10.1007/s00018‐016‐2223‐0. G. Cheng, R. Kong, L. Zhang, and J. Zhang, “Mitochondria in Traumatic Brain Injury and Mitochondrial‐Targeted Multipotential Therapeutic Strategies,” British Journal of Pharmacology 167, no. 4 (2012): 699–719, https://doi.org/10.1111/j.1476‐5381.2012.02025.x. Y. Xiong, P. L. Peterson, and C. P. Lee, “Alterations in Cerebral Energy Metabolism Induced by Traumatic Brain Injury,” Neurological Research 23, no. 2‐3 (2001): 129–138, https://doi.org/10.1179/016164101101198460. D. Belov Kirdajova, J. Kriska, J. Tureckova, and M. Anderova, “Ischemia‐Triggered Glutamate Excitotoxicity from the Perspective of Glial Cells,” Frontiers in Cellular Neuroscience 14 (2020): 51–51, https://doi.org/10.3389/fncel.2020.00051. M. Prins, T. Greco, D. Alexander, and C. C. Giza, “The Pathophysiology of Traumatic Brain Injury at a Glance,” Disease Models & Mechanisms 6, no. 6 (2013): 1307–1315. A. Corcoran and T. G. Cotter, “Redox Regulation of Protein Kinases,” The FEBS Journal 280, no. 9 (2013): 1944–1965, https://doi.org/10.1111/febs.12224. T. H. Truong and K. S. Carroll, “Redox Regulation of Protein Kinases,” Critical Reviews in Biochemistry and Molecular Biology 48, no. 4 (2013): 332–356, https://doi.org/10.3109/10409238.2013.790873. G. G. Chiang and R. T. Abraham, “Phosphorylation of Mammalian Target of Rapamycin (mTOR) at Ser‐2448 IsMediated by p70S6 Kinase,” Journal of Biological Chemistry 280, no. 27 (2005): 25485–25490, https://doi.org/10.1074/jbc.M501707200. E. Calabrese, A. Badea, G. Cofer, Y. Qi, and G. A. Johnson, “A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison With Neuronal Tracer Data,” Cerebral Cortex 25, no. 11 (2015): 4628–4637, https://doi.org/10.1093/cercor/bhv121. F. Clausen, N. Marklund, A. Lewén, et al., “Interstitial F 2 ‐Isoprostane 8‐Iso‐PGF 2α As a Biomarker of Oxidative Stress After Severe Human Traumatic Brain Injury,” Journal of Neurotrauma 29, no. 5 (2012): 766–775, https://doi.org/10.1089/neu.2011.1754. E. D. Hall, J. A. Wang, D. M. Miller, J. E. Cebak, and R. L. Hill, “Newer Pharmacological Approaches for Antioxidant Neuroprotection in Traumatic Brain Injury,” Neuropharmacology 145, no. Pt B (2019): 247–258, https://doi.org/10.1016/j.neuropharm.2018.08.005. B. Z. McDonald, C. C. Gee, and F. M. Kievit, “The Nanotheranostic Researcher's Guide for Use of Animal Models of Traumatic Brain Injury,” Journal of Nanotheranostics 2, no. 4 (2021): 224–268, https://doi.org/10.3390/jnt2040014. F. Pischiutta, E. Micotti, J. R. Hay, et al., “Single Severe Traumatic Brain Injury Produces Progressive Pathology With Ongoing Contralateral White Matter Damage One Year After Injury,” Experimental Neurology 300 (2018): 167–178, https://doi.org/10.1016/j.expneurol.2017.11.003. Y. L. Liu, F. Yuan, D. X. Yang, et al., “Adjudin Attenuates Cerebral Edema and Improves Neurological Function in Mice With Experimental Traumatic Brain Injury,” Journal of Neurotrauma 35, no. 23 (2018): 2850–2860, https://doi.org/10.1089/neu.2017.5397. M. D. Laird, S. Sukumari‐Ramesh, A. E. Swift, S. E. Meiler, J. R. Vender, and K. M. Dhandapani, “Curcumin Attenuates Cerebral Edema Following Traumatic Brain Injury in Mice: A Possible Role for Aquaporin‐4?,” Journal of Neurochemistry 113, no. 3 (2010): 637–648, https://doi.org/10.1111/j.1471‐4159.2010.06630.x. X. Mao, N. A. Terpolilli, A. Wehn, et al., “Progressive Histopathological Damage Occurring up to One Year After Experimental Traumatic Brain Injury Is Associated With Cognitive Decline and Depression‐Like Behavior,” Journal of Neurotrauma 37, no. 11 (2020): 1331–1341, https://doi.org/10.1089/neu.2019.6510. S. Hu, C. Exner, R. I. Sienel, et al., “Characterization of Vasogenic and Cytotoxic Brain Edema Formation after Experimental Traumatic Brain Injury by Free Water Diffusion Magnetic Resonance Imaging,” Journal of Neurotrauma 41, no. 3‐4 (2024): 393–406, https://doi.org/10.1089/neu.2023.0222. D. J. K. Loane, A. Kumar, B. A. Stoica, R. Cabatbat, and A. I. Faden, “Progressive Neurodegeneration After Experimental Brain Trauma: Association With Chronic Microglial Activation,” Journal of Neuropathology & Experimental Neurology 73, no. 1 (2014): 14–29, https://doi.org/10.1097/NEN.0000000000000021. S. Sharma, I. Ifergan, J. E. Kurz, et al., “Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury,” Annals of Neurology 87, no. 3 (2020): 442–455. R. Bertossi, J. E. Kurz, T. McGuire, C. Y. Peng, and J. A. Kessler, “Intravenous Immunomodulatory Nanoparticles Prevent Secondary Damage After Traumatic Brain Injury,” Journal of Neurotrauma 42, no. 1‐2 (2024): 94–106. G. Zhu, X. Wang, L. Chen, et al., “Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies,” Frontiers in Immunology 13 (2022): 852416. Z.‐G. Cheng, G.‐D. Zhang, P.‐Q. Shi, and B.‐S. Du, “Expression and Antioxidation of Nrf2/ARE Pathway in Traumatic Brain Injury,” Asian Pacific Journal of Tropical Medicine 6, no. 4 (2013): 305–310, https://doi.org/10.1016/S1995‐7645(13)60061‐9. W. Yan, H. D. Wang, Z. G. Hu, Q. F. Wang, and H. X. Yin, “Activation of Nrf2–ARE Pathway in Brain After Traumatic Brain Injury,” Neuroscience Letters 431, no. 2 (2008): 150–154, https://doi.org/10.1016/j.neulet.2007.11.060. Y. Zhou, M. Tian, H.‐D. Wang, et al., “Activation of the Nrf2‐ARE Signal Pathway After Blast Induced Traumatic Brain Injury in Mice,” International Journal of Neuroscience 129, no. 8 (2019): 801–807, https://doi.org/10.1080/00207454.2019.1569652. D. Xia, X. Zhai, H. Wang, Z. Chen, C. Fu, and M. Zhu, “Alpha Lipoic Acid Inhibits Oxidative Stress‐Induced Apoptosis by Modulating of Nrf2 Signalling Pathway After Traumatic Brain Injury,” Journal of Cellular and Molecular Medicine 23, no. 6 (2019): 4088–4096, https://doi.org/10.1111/jcmm.14296. L. Zhang, H. Wang, Y. Fan, et al., “Fucoxanthin Provides Neuroprotection in Models of Traumatic Brain Injury via the Nrf2‐ARE and Nrf2‐Autophagy Pathways,” Scientific Reports 7, no. 1 (2017): 1–15. H. Zhu, K. Itoh, M. Yamamoto, J. L. Zweier, and Y. Li, “Role of Nrf2 Signaling in Regulation of Antioxidants and Phase 2 Enzymes in Cardiac Fibroblasts: Protection Against Reactive Oxygen and Nitrogen Species‐Induced Cell Injury,” FEBS Letters 579, no. 14 (2005): 3029–3036, https://doi.org/10.1016/j.febslet.2005.04.058. S. Dinić, N. Grdović, A. Uskoković, et al., “CXCL12 Protects Pancreatic β‐Cells From Oxidative Stress by a Nrf2‐Induced Increase in Catalase Expression and Activity,” Proceedings of the Japan Academy, Series B 92, no. 9 (2016): 436–454. J. Yang, Q. Wu, S. Lan, et al., “Peroxiredoxin‐5 Alleviates Early Brain Injury After Subarachnoid Hemorrhage by Reducing Oxidative Stress,” Brain Research Bulletin 217 (2024): 111087, https://doi.org/10.1016/j.brainresbull.2024.111087. G. A. Brooks and N. A. Martin, “Cerebral Metabolism Following Traumatic Brain Injury: New Discoveries With Implications for Treatment,” Frontiers in Neuroscience 8 (2015): 408, https://doi.org/10.3389/fnins.2014.00408. J. B. Hiebert, Q. Shen, A. R. Thimmesch, and J. D. Pierce, “Traumatic Brain Injury and Mitochondrial Dysfunction,” The American Journal of the Medical Sciences 350, no. 2 (2015): 132–138, https://doi.org/10.1097/MAJ.0000000000000506. S. Yoshida, S. Hong, T. Suzuki, et al., “Redox Regulates Mammalian Target of Rapamycin Complex 1 (mTORC1) Activity by Modulating the TSC1/TSC2‐Rheb GTPase Pathway,” Journal of Biological Chemistry 286, no. 37 (2011): 32651–32660, https://doi.org/10.1074/jbc.M111.238014. D. Shao, S.‐I. Oka, T. Liu, et al., “A Redox‐Dependent Mechanism for Regulation of AMPK Activation by Thioredoxin1 During Energy Starvation,” Cell Metabolism 19, no. 2 (2014): 232–245, https://doi.org/10.1016/j.cmet.2013.12.013. L. Zhang, Z. Xu, Z. Jia, et al., “Modulating mTOR‐Dependent Astrocyte Substate Transitions to Alleviate Neurodegeneration,” Nature Aging 5, no. 3 (2025): 468–485, https://doi.org/10.1038/s43587‐024‐00792‐z. L. Hochmuth and J. Hirrlinger, “Physiological and Pathological Role of mTOR Signaling in Astrocytes,” Neurochemical Research 50, no. 1 (2025): 53, https://doi.org/10.1007/s11064‐024‐04306‐6. S. Erlich, A. Alexandrovich, E. Shohami, and R. Pinkas‐Kramarski, “Rapamycin Is a Neuroprotective Treatment for Traumatic Brain Injury,” Neurobiology of Disease 26, no. 1 (2007): 86–93, https://doi.org/10.1016/j.nbd.2006.12.003. I. Nikolaeva, B. Crowell, J. Valenziano, D. Meaney, and G. D'Arcangelo, “Beneficial Effects of Early mTORC1 Inhibition After Traumatic Brain Injury,” Journal of Neurotrauma 33, no. 2 (2016): 183–193, https://doi.org/10.1089/neu.2015.3899. M. Campolo, G. Casili, M. Lanza, et al., “The Inhibition of Mammalian Target of Rapamycin (mTOR) in Improving Inflammatory Response After Traumatic Brain Injury,” Journal of Cellular and Molecular Medicine 25, no. 16 (2021): 7855–7866, https://doi.org/10.1111/jcmm.16702. C. L. Mac Donald, K. Dikranian, P. Bayly, D. Holtzman, and D. Brody, “Diffusion Tensor Imaging Reliably Detects Experimental Traumatic Axonal Injury and Indicates Approximate Time of Injury,” Journal of Neuroscience 27, no. 44 (2007): 11869–11876. E. B. Hutchinson, S. C. Schwerin, K. L. Radomski, M. O. Irfanoglu, S. L. Juliano, and C. M. Pierpaoli, “Quantitative MRI and DTI Abnormalities During the Acute Period Following CCI in the Ferret,” Shock 46, no. 1 (2016): 167–176. E. B. Hutchinson, S. C. Schwerin, A. V. Avram, S. L. Juliano, and C. Pierpaoli, “Diffusion MRI and the Detection of Alterations Following Traumatic Brain Injury,” Journal of Neuroscience Research 96, no. 4 (2018): 612–625, https://doi.org/10.1002/jnr.24065. M. D. Budde, L. Janes, E. Gold, L. C. Turtzo, and J. A. Frank, “The Contribution of Gliosis to Diffusion Tensor Anisotropy and Tractography Following Traumatic Brain Injury: Validation in the Rat Using Fourier Analysis of Stained Tissue Sections,” Brain 134, no. Pt 8 (2011): 2248–2260, https://doi.org/10.1093/brain/awr161. N. G. Harris, D. R. Verley, B. A. Gutman, and R. L. Sutton, “Bi‐Directional Changes in Fractional Anisotropy After Experiment TBI: Disorganization and Reorganization?,” Neuroimage 133 (2016): 129–143, https://doi.org/10.1016/j.neuroimage.2016.03.012. F. C. Yeh, A. Irimia, D. C. A. Bastos, and A. J. Golby, “Tractography Methods and Findings in Brain Tumors and Traumatic Brain Injury,” Neuroimage 245 (2021): 118651, https://doi.org/10.1016/j.neuroimage.2021.118651. J. M. Soares, P. Marques, V. Alves, and N. Sousa, “A Hitchhiker's Guide to Diffusion Tensor Imaging,” Frontiers in Neuroscience 7 (2013): 31. Z. Kou and P. J. VandeVord, “Traumatic White Matter Injury and Glial Activation: From Basic Science to Clinics,” Glia 62, no. 11 (2014): 1831–1855, https://doi.org/10.1002/glia.22690. J. Styrke, B.‐M. Stålnacke, P. Sojka, and U. Björnstig, “Traumatic Brain Injuries in a Well‐Defined Population: Epidemiological Aspects and Severity,” Journal of Neurotrauma 24, no. 9 (2007): 1425–1436, https://doi.org/10.1089/neu.2007.0266. G.‐F. Yu, Y.‐Q. Jie, A. Wu, Q. Huang, W.‐M. Dai, and X.‐F. Fan, “Increased Plasma 8‐Iso‐Prostaglandin F2α Concentration in Severe Human Traumatic Brain Injury,” Clinica Chimica Acta 421 (2013): 7–11, https://doi.org/10.1016/j.cca.2013.02.030. J. T. Cole, A. Yarnell, W. S. Kean, et al., “Craniotomy: True Sham for Traumatic Brain Injury, or a Sham of a Sham?,” Journal of Neurotrauma 28, no. 3 (2011): 359–369, https://doi.org/10.1089/neu.2010.1427. C. Santana‐Gomez, G. Smith, A. Mousavi, M. Shamas, N. G. Harris, and R. Staba, “The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation, and Behavior in a Traumatic Brain Injury Animal Model,” Neurotrauma Reports 5, no. 1 (2024): 969–981, https://doi.org/10.1089/neur.2024.0064. A. W. Tarudji, B. Z. McDonald, E. Curtis, C. Gee, and F. M. Kievit, “Structural Defects Associated With Craniectomy Induce Neuroinflammation and Blood–Brain Barrier Permeability,” Neurotrauma Reports 6, no. 1 (2025): 586–599, https://doi.org/10.1177/08977151251362176. |
| Grant Information: | R01NS109488 National Institute of Neurological Disorders and Stroke of the National Institutes of Health; T32 GM136593 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: cellular metabolism; nanoparticles; oxidative stress; traumatic brain injury; vasogenic edema |
| Substance Nomenclature: | 0 (Neuroprotective Agents) 0 (Polymers) 0 (Sulfhydryl Compounds) 0 (Reactive Oxygen Species) 0 (Antioxidants) 0 (NF-E2-Related Factor 2) 0 (Glial Fibrillary Acidic Protein) |
| Entry Date(s): | Date Created: 20260721 Date Completed: 20260721 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13387508 |
| DOI: | 10.1002/mabi.202500642 |
| PMID: | 42479781 |
| Βάση Δεδομένων: | MEDLINE |
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