Lennicke, C. & Cochemé, H. M. Redox metabolism: ROS as specific molecular regulators of cell signaling and function. Mol. Cell 81, 3691–3707 (2021).
Google Scholar
Butterfield, D. A. & Halliwell, B. Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat. Rev. Neurosci. 20, 148–160 (2019).
Google Scholar
Schumacher, B., Pothof, J., Vijg, J. & Hoeijmakers, J. H. J. The central role of DNA damage in the ageing process. Nature 592, 695–703 (2021).
Google Scholar
Burton, G. W. & Ingold, K. U. Autoxidation of biological molecules. 1. Antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J. Am. Chem. Soc. 103, 6472–6477 (1981).
Google Scholar
Yamamoto, Y. et al. Free radical chain oxidation and hemolysis of erythrocytes by molecular oxygen and their inhibition by vitamin E. J. Nutr. Sci. Vitaminol. 32, 475–479 (1986).
Google Scholar
Rodrigo, J., Fernández, A. P., Serrano, J., Peinado, M. A. & Martínez, A. The role of free radicals in cerebral hypoxia and ischemia. Free Radic. Biol. Med. 39, 26–50 (2005).
Google Scholar
Yoshida, S. et al. Influence of transient ischemia on lipid-soluble antioxidants, free fatty acids and energy metabolites in rat brain. Brain Res. 245, 307–316 (1982).
Google Scholar
Butterfield, D. A. & Boyd-Kimball, D. Oxidative stress, amyloid-β peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer’s disease. J. Alzheimer’s Dis. 62, 1345–1367 (2018).
Google Scholar
Hensley, K. et al. Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J. Neurochem. 65, 2146–2156 (1995).
Google Scholar
Martins, R. N., Harper, C. G., Stokes, G. B. & Masters, C. L. Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer’s disease may reflect oxidative stress. J. Neurochem. 46, 1042–1045 (1986).
Google Scholar
Arnold, S. E. et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat. Rev. Neurol. 14, 168–181 (2018).
Google Scholar
Weise, C. M. et al. Left lateralized cerebral glucose metabolism declines in amyloid-β positive persons with mild cognitive impairment. NeuroImage Clin. 20, 286–296 (2018).
Google Scholar
Smith, M. A., Harris, P. L. R., Sayre, L. M., Beckman, J. S. & Perry, G. Widespread peroxynitrite-mediated damage in Alzheimer’s disease. J. Neurosci. 17, 2653–2657 (1997).
Google Scholar
Sultana, R. et al. Proteomic identification of nitrated brain proteins in amnestic mild cognitive impairment: a regional study. J. Cell. Mol. Med. 11, 839–851 (2007).
Google Scholar
Reed, T. T., Pierce, W. M. Jr, Turner, D. M., Markesbery, W. R. & Butterfield, D. A. Proteomic identification of nitrated brain proteins in early Alzheimer’s disease inferior parietal lobule. J. Cell. Mol. Med. 13, 2019–2029 (2009).
Google Scholar
Mattson, M. P. Pathways towards and away from Alzheimer’s disease. Nature 430, 631–639 (2004).
Google Scholar
Petersen, R. C. et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med. 352, 2379–2388 (2005).
Google Scholar
Murphy, M. P. et al. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nat. Metab. 4, 651–662 (2022).
Google Scholar
Swartz, H. M. et al. Clinical EPR unique opportunities and some challenges. Acad. Radiol. 21, 197–206 (2014).
Google Scholar
Keshari, K. R. et al. Hyperpolarized 13C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging. Proc. Natl Acad. Sci. USA 108, 18606–18611 (2011).
Google Scholar
Carroll, V. et al. A boronate-caged [18F]FLT probe for hydrogen peroxide detection using positron emission tomography. J. Am. Chem. Soc. 136, 14742–14745 (2014).
Google Scholar
Carroll, V. N. et al. [11C]Ascorbic and [11C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem. Commun. 52, 4888–4890 (2016).
Google Scholar
Pisaneschi, F., Gammon, S. T., Paolillo, V., Qureshy, S. A. & Piwnica-Worms, D. Imaging of innate immunity activation in vivo with a redox-tuned PET reporter. Nat. Biotechnol. 40, 965–973 (2022).
Google Scholar
Hou, C. et al. Development of a positron emission tomography radiotracer for imaging elevated levels of superoxide in neuroinflammation. ACS Chem. Neurosci. 9, 578–586 (2018).
Google Scholar
Wilson, A. A. et al. Evaluation of a novel radiotracer for positron emission tomography imaging of reactive oxygen species in the central nervous system. Nucl. Med. Biol. 53, 14–20 (2017).
Google Scholar
Okazawa, H. et al. Cerebral oxidative stress in early Alzheimer’s disease evaluated by 64Cu-ATSM PET/MRI: a preliminary study. Antioxidants 11, 1022 (2022).
Google Scholar
Watanabe, K., Tanaka, M., Yuki, S., Hirai, M. & Yamamoto, Y. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J. Clin. Biochem. Nutr. 62, 20–38 (2018).
Google Scholar
Fujisawa, A. & Yamamoto, Y. Edaravone, a potent free radical scavenger, reacts with peroxynitrite to produce predominantly 4-NO-edaravone. Redox Rep. 21, 98–103 (2016).
Google Scholar
Radi, R. Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine. Proc. Natl Acad. Sci. USA 115, 5839–5848 (2018).
Google Scholar
Kawai, H. et al. Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in the rat distal middle cerebral artery occlusion model. J. Pharmacol. Exp. Ther. 281, 921–927 (1997).
Google Scholar
Kobayashi, S., Fukuma, S., Ikenoue, T., Fukuhara, S. & Kobayashi, S. Effect of edaravone on neurological symptoms in real-world patients with acute ischemic stroke. Stroke 50, 1805–1811 (2019).
Google Scholar
Witzel, S. et al. Safety and effectiveness of long-term intravenous administration of edaravone for treatment of patients with amyotrophic lateral sclerosis. JAMA Neurol. 79, 121–130 (2022).
Google Scholar
Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351 (2007).
Google Scholar
Nebel, N. et al. [18F]Fluorophenylazocarboxylates: design and synthesis of potential radioligands for dopamine D3 and μ-opioid receptor. ACS Omega 2, 8649–8659 (2017).
Google Scholar
Roy, A. & Sil, P. C. Tertiary butyl hydroperoxide induced oxidative damage in mice erythrocytes: protection by taurine. Pathophysiology 19, 137–148 (2012).
Google Scholar
Roy, A. & Sil, P. C. Taurine protects murine hepatocytes against oxidative stress-induced apoptosis by tert-butyl hydroperoxide via PI3K/AKT and mitochondrial-dependent pathways. Food Chem. 131, 1086–1096 (2012).
Google Scholar
Jong, C. J., Azuma, J. & Schaffer, S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42, 2223–2232 (2012).
Google Scholar
Chu, W. et al. Development of a PET radiotracer for non-invasive imaging of the reactive oxygen species, superoxide, in vivo. Org. Biomol. Chem. 12, 4421–4431 (2014).
Google Scholar
Rauhala, P., Andoh, T., Yeh, K. & Chiueh, C. C. Contradictory effects of sodium nitroprusside and S-nitroso-N-acetylpenicillamine on oxidative stress in brain dopamine neurons in vivo. Ann. N. Y. Acad. Sci. 962, 60–72 (2002).
Google Scholar
Sun, Y.-Y. et al. A murine photothrombotic stroke model with an increased fibrin content and improved responses to tPA-lytic treatment. Blood Adv. 4, 1222–1231 (2020).
Google Scholar
Sun, Y.-Y. et al. Prophylactic edaravone prevents transient hypoxic-ischemic brain injury: implications for perioperative neuroprotection. Stroke 46, 1947–1955 (2015).
Google Scholar
Kessler, R. M. et al. Measurement of blood–brain barrier permeability with positron emission tomography and [68Ga]EDTA. J. Cereb. Blood Flow Metab. 4, 323–328 (1984).
Google Scholar
Li, Y. & Kundu, B. K. An improved optimization algorithm of the three-compartment model with spillover and partial volume corrections for dynamic FDG PET images of small animal hearts in vivo. Phys. Med. Biol. 63, 055003 (2018).
Google Scholar
Logan, J. et al. Graphical analysis of reversible radioligand binding from time–activity measurements applied to [N-11C-methyl]-cocaine PET studies in human subjects. J. Cereb. Blood Flow Metab. 10, 740–747 (1990).
Google Scholar
Quigg, M. & Kundu, B. Dynamic FDG-PET demonstration of functional brain abnormalities. Ann. Clin. Transl. Neurol. 9, 1487–1497 (2022).
Google Scholar
Massey, J. C. et al. Model corrected blood input function to compute cerebral FDG uptake rates from dynamic total-body PET images of rats in vivo. Front. Med. 8, 618645 (2021).
Google Scholar
Dumont, M. et al. Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. FASEB J. 25, 4063–4072 (2011).
Google Scholar
Blennow, K. & Zetterberg, H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J. Intern. Med. 284, 643–663 (2018).
Google Scholar
Villa, C., Lavitrano, M., Salvatore, E. & Combi, R. Molecular and imaging biomarkers in Alzheimer’s disease: a focus on recent insights. J. Pers. Med. 10, 61 (2020).
Google Scholar
Young, P. N. E. et al. Imaging biomarkers in neurodegeneration: current and future practices. Alzheimer’s Res. Ther. 12, 49 (2020).
Google Scholar
Haque, R. et al. A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer’s disease. Sci. Transl. Med. 15, eadg4122 (2023).
Google Scholar
Ward, J., Ly, M. & Raji, C. A. Brain PET imaging frontotemporal dementia. PET Clin. 18, 123–133 (2023).
Google Scholar
Wilson, D. M. et al. Hallmarks of neurodegenerative diseases. Cell 186, 693–714 (2023).
Google Scholar
Branca, C. et al. Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer’s disease. Hum. Mol. Genet. 26, 4823–4835 (2017).
Google Scholar
Scott, P. J. H. et al. Studies into radiolytic decomposition of fluorine-18 labeled radiopharmaceuticals for positron emission tomography. Appl. Radiat. Isot. 67, 88–94 (2009).
Google Scholar
Neumann, K. D. et al. Dose formulation, biodistribution and PET imaging studies of a first-in-class fluorine-18 organophosphorus cholinesterase inhibitor tracer in rat. Curr. Chem. Biol. 14, 289–303 (2020).
Google Scholar
Murakami, K. et al. Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J. Neurosci. 18, 205–213 (1998).
Google Scholar
Sun, Y.-Y. et al. Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke. PLoS ONE 9, e98807 (2014).
Google Scholar
Furuya, D. et al. Edaravone therapy initiated immediately after cardioembolic stroke and its effects on functional recovery. Nosotchu 28, 291–296 (2006).
Google Scholar
Patlak, C. S. & Blasberg, R. G. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J. Cereb. Blood Flow Metab. 5, 584–590 (1985).
Google Scholar
Gallivanone, F., Rosa, P. A. D. & Castiglioni, I. Statistical voxel-based methods and [18F]FDG PET brain imaging: frontiers for the diagnosis of AD. Curr. Alzheimer Res. 13, 682–694 (2016).
Google Scholar
Hsieh, C.-J. et al. [18F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer’s disease pathology in APP/PS1 mice. EJNMMI Res. 12, 43–55 (2022).
Dickinson, B. C. & Chang, C. J. A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells. J. Am. Chem. Soc. 130, 11561–11561 (2008).
Google Scholar
Luanpitpong, S. et al. Mitochondrial superoxide mediates doxorubicin-induced keratinocyte apoptosis through oxidative modification of ERK and Bcl-2 ubiquitination. Biochem. Pharmacol. 83, 1643–1654 (2012).
Google Scholar
Hosoi, R. et al. A simple ex vivo semiquantitative fluorescent imaging utilizing planar laser scanner: detection of reactive oxygen species generation in mouse brain and kidney. Mol. Imaging 18, 1536012118820421 (2019).
Google Scholar
Huang, Q., Massey, J. C., Mińczuk, K., Li, J. & Kundu, B. K. Non-invasive determination of blood input function to compute rate of myocardial glucose uptake from dynamic FDG PET images of rat heart in vivo: comparative study between the inferior vena cava and the left ventricular blood pool with spill over and partial volume corrections. Phys. Med. Biol. 64, 165010–165018 (2019).
Google Scholar
Zhong, M. & Kundu, B. K. Optimization of a model corrected blood input function from dynamic FDG-PET images of small animal heart in vivo. IEEE Trans. Nucl. Sci. 60, 3417–3422 (2013).
Google Scholar
Neumann, K. D. et al. Microglial activation persists beyond clinical recovery following sport concussion in collegiate athletes. Front. Neurol. 14, 1127708 (2023).
Google Scholar