{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:36:35Z","timestamp":1790710595900,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["Grants VEGA 1\/0171\/18, VEGA 1\/0230\/20,"],"award-info":[{"award-number":["Grants VEGA 1\/0171\/18, VEGA 1\/0230\/20,"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["VEGA 1\/0171\/18, VEGA 1\/0230\/20,"],"award-info":[{"award-number":["VEGA 1\/0171\/18, VEGA 1\/0230\/20,"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hyperhomocysteinemia (hHcy) represents a strong risk factor for atherosclerosis-associated diseases, like stroke, dementia or Alzheimer\u2019s disease. A methionine (Met)-rich diet leads to an elevated level of homocysteine in plasma and might cause pathological alterations across the brain. The hippocampus is being constantly studied for its selective vulnerability linked with neurodegeneration. This study explores metabolic and histo-morphological changes in the rat hippocampus after global ischemia in the hHcy conditions using a combination of proton magnetic resonance spectroscopy and magnetic resonance-volumetry as well as immunohistochemical analysis. After 4 weeks of a Met-enriched diet at a dose of 2 g\/kg of animal weight\/day, adult male Wistar rats underwent 4-vessel occlusion lasting for 15 min, followed by a reperfusion period varying from 3 to 7 days. Histo-morphological analyses showed that the subsequent ischemia-reperfusion insult (IRI) aggravates the extent of the sole hHcy-induced degeneration of the hippocampal neurons. Decreased volume in the grey matter, extensive changes in the metabolic ratio, deeper alterations in the number and morphology of neurons, astrocytes and their processes were demonstrated in the hippocampus 7 days post-ischemia in the hHcy animals. Our results suggest that the combination of the two risk factors (hHcy and IRI) endorses and exacerbates the rat hippocampal neurodegenerative processes.<\/jats:p>","DOI":"10.3390\/biom10081128","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T04:15:31Z","timestamp":1596168931000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of Methionine Diet on Time-Related Metabolic and Histopathological Changes of Rat Hippocampus in the Model of Global Brain Ischemia"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria","family":"Kovalska","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-1675","authenticated-orcid":false,"given":"Petra","family":"Hnilicova","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Kalenska","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"},{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tomascova","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Adamkov","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lehotsky","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"},{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.neulet.2011.02.076","article-title":"Methionine diet-induced hyperhomocysteinemia accelerates cerebral aneurysm formation in rats","volume":"494","author":"Xu","year":"2011","journal-title":"Neurosci. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12603-014-0534-0","article-title":"Nutrient patterns and brain biomarkers of Alzheimer\u2019s disease in cognitively normal individuals","volume":"19","author":"Berti","year":"2015","journal-title":"J. Nutr. Health Aging"},{"key":"ref_3","first-page":"117","article-title":"A novel rat model of heart failure induced by high methionine diet showing evidence of association between hyperhomocysteinemia and activation of NF-kappaB","volume":"8","author":"Liu","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Esse, R., Barroso, M., de Almeida, I.T., and Castro, R. (2019). The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040867"},{"key":"ref_5","unstructured":"Pluta, R. (2019). Ischemic brain injury in hyperhomocysteinemic conditions and the development of Alzheimer\u2019s disease. Brain Ischemia: Alzheimer\u2019s Disease Mechanisms, Nova Science Pub Inc.. [1st ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00726-019-02814-2","article-title":"Hypermethioninemia induces memory deficits and morphological changes in hippocampus of young rats: Implications on pathogenesis","volume":"52","author":"Soares","year":"2020","journal-title":"Amino Acids"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nchembio.1787","article-title":"Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors","volume":"11","author":"Tarrago","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38299","DOI":"10.1038\/srep38299","article-title":"Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress","volume":"6","author":"Suzuki","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.ijdevneu.2005.06.003","article-title":"Methionine alters Na+,K+-ATPase activity, lipid peroxidation and nonenzymatic antioxidant defenses in rat hippocampus","volume":"23","author":"Stefanello","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneumeth.2006.07.029","article-title":"Chemically induced model of hypermethioninemia in rats","volume":"160","author":"Stefanello","year":"2007","journal-title":"J. Neurosci. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1007\/s11011-017-0054-9","article-title":"Acute administration of methionine and\/or methionine sulfoxide impairs redox status and induces apoptosis in rat cerebral cortex","volume":"32","author":"Soares","year":"2007","journal-title":"Metab. Brain Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1021\/acschemneuro.8b00310","article-title":"Amyloid-like Structures Formed by Single Amino Acid Self-Assemblies of Cysteine and Methionine","volume":"10","author":"Gour","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1096\/fj.201701127R","article-title":"Methionine oxidized apolipoprotein A-I at the crossroads of HDL biogenesis and amyloid formation","volume":"32","author":"Witkowski","year":"2018","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1681\/ASN.2012050536","article-title":"Cognitive Disorders and Dementia in CKD: The Neglected Kidney-Brain Axis","volume":"24","author":"Bugnicourt","year":"2013","journal-title":"JASN"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.bbadis.2015.11.015","article-title":"Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID)","volume":"1862","author":"Hainsworth","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12974-019-1685-z","article-title":"Time course of neuropathological events in hyperhomocysteinemic amyloid depositing mice reveals early neuroinflammatory changes that precede amyloid changes and cerebrovascular events","volume":"16","author":"Weekman","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"587","DOI":"10.2217\/fnl.11.42","article-title":"Cerebral microbleeds: Detection, mechanisms and clinical challenges","volume":"6","author":"Charidimou","year":"2011","journal-title":"Future Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100916","DOI":"10.1016\/j.arr.2019.100916","article-title":"Inflammation and cerebral small vessel disease: A systematic review","volume":"53","author":"Low","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/02699052.2020.1725835","article-title":"Traumatic microbleeds persist for up to five years following traumatic brain injury despite resolution of other acute findings on MRI","volume":"34","author":"Rizk","year":"2020","journal-title":"Brain Injury"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kovalska, M., Hnilicova, P., Kalenska, D., Tothova, B., Adamkov, M., and Lehotsky, J. (2019). Effect of Methionine Diet on Metabolic and Histopathological Changes of Rat Hippocampus. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246234"},{"key":"ref_21","first-page":"887","article-title":"Combination of hyperhomocysteinemia and ischemic tolerance in experimental model of global ischemia in rats","volume":"66","author":"Kovalska","year":"2015","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1007\/s11064-018-2592-x","article-title":"Association of Induced Hyperhomocysteinemia with Alzheimer\u2019s Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury","volume":"43","author":"Kovalska","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_23","first-page":"31","article-title":"Association of induced hyperhomocysteinemia with neurodegeneration in rat entorhinal cortex-hippocampal system after global brain ischemia: A progression of Alzheimer\u2019s disease-like pathological features?","volume":"61","author":"Kovalska","year":"2019","journal-title":"Act. Nerv. Super. Rediviva"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"T\u00f3thov\u00e1, B., Kovalsk\u00e1, M., Kalensk\u00e1, D., Toma\u0161cov\u00e1, A., and Lehotsk\u00fd, J. (2018). Histone Hyperacetylation as a Response to Global Brain Ischemia Associated with Hyperhomocysteinemia in Rats. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103147"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/ana.410110509","article-title":"Temporal profile of neuronal damage in a model of transient forebrain ischemia","volume":"11","author":"Pulsinelli","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_26","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Academic Press. [6th ed.]."},{"key":"ref_27","first-page":"116","article-title":"Magnetic Resonance Imaging of Stroke in the Rat","volume":"31","author":"Ding","year":"2014","journal-title":"Bo Pu Xue Za Zhi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s12035-019-01799-z","article-title":"Expression of the Tau Protein and Amyloid Protein Precursor Processing Genes in the CA3 Area of the Hippocampus in the Ischemic Model of Alzheimer\u2019s Disease in the Rat","volume":"57","author":"Pluta","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Newrezella, D., Pahlavan, P.S., Kr\u00fcger, C., Boehm, C., Sorgenfrei, O., Schr\u00f6ck, H., Eisenhardt, G., Bischoff, N., Vogt, G., and Wafzig, O. (2007). The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia. BMC Genom., 8.","DOI":"10.1186\/1471-2164-8-370"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pneurobio.2013.11.005","article-title":"Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance","volume":"114","author":"Stetler","year":"2014","journal-title":"Prog Neurobiol."},{"key":"ref_31","first-page":"538","article-title":"Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance","volume":"10","author":"Dobrota","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s12031-011-9695-z","article-title":"Tetrahydrocurcumin ameliorates homocysteinylated cytochrome-c mediated autophagy in hyperhomocysteinemia mice after cerebral ischemia","volume":"47","author":"Tyagi","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00424-016-1849-y","article-title":"Hyperhomocysteinemia impairs regional blood flow: Involvements of endothelial and neuronal nitric oxide","volume":"468","author":"Toda","year":"2016","journal-title":"Pflugers Arch."},{"key":"ref_34","first-page":"767","article-title":"p-ERKinvolvement in the neuroprotection exerted by ischemic preconditioning in rat hippocampus subjected to four vessel occlusion","volume":"65","author":"Kovalska","year":"2014","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s12640-017-9847-1","article-title":"Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative\/Nitrative Status and Causes Protein\/DNA Damage, as Well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?","volume":"33","author":"Moreira","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14814\/phy2.12292","article-title":"Long-term methionine-diet induced mild hyperhomocysteinemia associated cardiac metabolic dysfunction in multiparous rats","volume":"3","author":"Song","year":"2015","journal-title":"Physiol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s10571-019-00674-8","article-title":"Chronic mild Hyperhomocysteinemia impairs energy metabolism, promotes DNA damage and induces a Nrf2 response to oxidative stress in rats brain","volume":"39","author":"Siebert","year":"2019","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s11011-018-0298-z","article-title":"High methionine, low folate and low vitamin B6\/B12 (HM-LF-LV) diet causes neurodegeneration and subsequent short-term memory loss","volume":"33","author":"Nuru","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12974-017-1044-x","article-title":"F-VC701-PET and MRI in the in vivo neuroinflammation assessment of a mouse model of multiple sclerosis","volume":"15","author":"Belloli","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a006213","article-title":"Brain Imaging in Alzheimer Disease","volume":"2","author":"Johnson","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"116458","DOI":"10.1016\/j.jns.2019.116458","article-title":"Altered hypothalamic metabolism in early multiple sclerosis\u2013MR spectroscopy study","volume":"407","author":"Dobrota","year":"2019","journal-title":"J. Neurol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bcp.2009.09.014","article-title":"Astrocytes in the damaged brain:molecular and cellular insights in to the irreactive response and healing potential","volume":"79","author":"Buffo","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00004647-200203000-00006","article-title":"High Sensitivity of Protoplasmic Cortical Astroglia to Focal Ischemia","volume":"22","author":"Lukaszevicz","year":"2002","journal-title":"J. Cerebral Blood Flow Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.ajpath.2013.02.031","article-title":"A phenotypic change but not proliferation underlies glial responses in Alzheimer disease","volume":"182","author":"Growdon","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.brainresbull.2017.02.001","article-title":"Human astrocytes in the diseased brain","volume":"136","author":"Dossi","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759091417742296","article-title":"Hyperhomocysteinemia-Induced Gene Expression Changes in the Cell Types of the Brain","volume":"9","author":"Weekman","year":"2017","journal-title":"ASN Neuro"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0304-3940(03)00655-4","article-title":"Homocysteine induces cell death of ratastrocytes in vitro","volume":"347","author":"Maler","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s12031-018-1120-4","article-title":"Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes","volume":"65","author":"Cervetto","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Skowro\u0144ska, K., Obara-Michlewska, M., Zieli\u0144ska, M., and Albrecht, J. (2019). NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020309"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.mri.2013.03.026","article-title":"Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation","volume":"31","author":"Huang","year":"2013","journal-title":"Magn Reson Imaging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1148\/radiol.13130531","article-title":"Clinical Proton MR spectroscopy in central nervous system Disorders","volume":"270","author":"Alger","year":"2014","journal-title":"Radiology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.crad.2008.07.002","article-title":"Magnetic resonance spectroscopy of the brain: Review of metabolites and clinical applications","volume":"64","author":"Soares","year":"2009","journal-title":"Clin. Radiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/00004647-199902000-00008","article-title":"N-Acetylaspartate Distribution in Rat Brain Striatum During Acute Brain Ischemia","volume":"19","author":"Sager","year":"1999","journal-title":"J. Cerebral Blood Flow Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1729071","DOI":"10.1155\/2018\/1729071","article-title":"Quantitative Radiomics: Impact of Pulse Sequence Parameter Selection on MRI-Based Textural Features of the Brain","volume":"2018","author":"Ford","year":"2018","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.nicl.2018.10.001","article-title":"In-vivo evaluation of neuronal and glial changes in amyotrophic lateral sclerosis with diffusion tensor spectroscopy","volume":"20","author":"Reischauer","year":"2018","journal-title":"NeuroImage Clin."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"807","DOI":"10.3389\/fneur.2019.00807","article-title":"Deciphering the Link Between Hyperhomocysteinemia and Ceramide Metabolism in Alzheimer-Type Neurodegeneration","volume":"10","author":"Kassis","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1089\/neu.2010.1739","article-title":"Early microstructural and metabolic changes following controlled cortical impact injury in rat: A magnetic resonance imaging and spectroscopy study","volume":"28","author":"Xu","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1038\/jcbfm.2012.114","article-title":"Altered neurochemical profile after traumatic brain injury: H-MRS biomarkers of pathological mechanisms","volume":"32","author":"Harris","year":"2012","journal-title":"J. Cereb Blood Flow Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/glia.10283","article-title":"Early loss of astrocytes after experimental Traumatic brain injury","volume":"44","author":"Zhao","year":"2003","journal-title":"Glia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s11481-013-9460-x","article-title":"Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain","volume":"8","author":"Chang","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fnagi.2015.00202","article-title":"Probing astrocyte metabolism in vivo: Proton magnetic resonance spectroscopy in the injured and aging brain","volume":"7","author":"Harris","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/j.1528-1167.2012.03685.x","article-title":"In vivo imaging of glia activation using 1H-magnetic resonance spectroscopy to detect putative biomarkers of tissue epileptogenicity","volume":"53","author":"Filibian","year":"2012","journal-title":"Epilepsia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6932","DOI":"10.1038\/s41598-017-07112-z","article-title":"Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1148\/radiol.2481071590","article-title":"Alzheimer disease: Postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements","volume":"248","author":"Kantarci","year":"2008","journal-title":"Radiology"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Per\u0142a-Kaj\u00e1n, J., and Jakubowski, H. (2019). Dysregulation of Epigenetic Mechanisms of Gene Expression in the Pathologies of Hyperhomocysteinemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133140"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e0171558","DOI":"10.1371\/journal.pone.0171558","article-title":"Evolution of blood-brain-barrier permeability after acute ischemic stroke","volume":"12","author":"Merali","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1038\/s41598-019-39263-6","article-title":"Multi-parameters of Magnetic Resonance Imaging to estimate Ischemia-Reperfusion Injury after stroke in Hyperglycemic Rats","volume":"9","author":"Huang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.redox.2018.09.021","article-title":"Homocysteine causes vascular endothelial dysfunction by disrupting endoplasmic reticulum redox homeostasis","volume":"20","author":"Wu","year":"2019","journal-title":"Redox Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.yjmcc.2011.12.009","article-title":"Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress","volume":"52","author":"Wang","year":"2012","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s11010-015-2588-7","article-title":"Effects of mild hyperhomocysteinemia on electron transport chain complexes, oxidative stress, and protein expression in rat cardiac mitochondria","volume":"411","author":"Timkova","year":"2016","journal-title":"Mol. Cell Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jcb.27603","article-title":"Remote ischemic conditioning as a cytoprotective strategy in vasculopathies during hyperhomocysteinemia: An emerging research perspective","volume":"120","author":"Majumder","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/jmri.10256","article-title":"MRI tissue characterization of experimental cerebral ischemia in rat","volume":"17","author":"Pasnoor","year":"2003","journal-title":"J. Magn. Reson. 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