{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:50:07Z","timestamp":1793508607138,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-34\/2026-03\/200113"],"award-info":[{"award-number":["451-03-34\/2026-03\/200113"]}]},{"award":["451-03-34\/2026-03\/200113"],"award-info":[{"award-number":["451-03-34\/2026-03\/200113"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Chemotherapy-induced cognitive impairment, colloquially known as chemobrain, affects a substantial proportion of cancer patients. Preclinical rodent models help clarify underlying drug-specific neurotoxic effects, as well as histological, biochemical, molecular, and behavioral mechanisms. Methods: We conducted a narrative review of animal studies examining cognitive dysfunction following treatment with commonly used chemotherapeutic agents, including doxorubicin, cisplatin, cyclophosphamide, methotrexate, 5-fluorouracil, paclitaxel, and docetaxel. The review focused on behavioral and cognitive outcomes, and experimental parameters such as rodent models and dosing regimens. Results: Across studies, chemotherapeutic exposure has had a consistent negative effect on short-term and working memory, learning and other cognitive domains, with impairments being often mild and detectable even at doses not causing apparent systemic toxicity. Histological analyses revealed reduced neurogenesis, dendritic and myelin alterations, and glial activation, mainly in the hippocampus and prefrontal cortex. Biochemical and molecular changes included oxidative stress, pro-apoptotic signaling, inflammatory cytokine dysregulation, decreased neurotrophic support, and altered neurotransmitter dynamics. Age and sex influenced susceptibility, with juvenile or aged animals and females\u2014particularly older females modeling breast cancer patients\u2014showing greater deficits. Cumulative or repeated dosing exacerbated neurotoxicity, while single administrations produced milder, sometimes transient, impairments. Conclusions: Preclinical models provide compelling evidence that chemotherapeutic agents impair cognitive function via convergent mechanisms involving inflammation, oxidative stress, and synaptic dysregulation. These findings highlight the importance of considering age, sex, and treatment schedule in designing neuroprotective strategies and underscore the translational relevance of rodent models in understanding chemobrain.<\/jats:p>","DOI":"10.3390\/brainsci16070750","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemotherapy-Induced Brain Damage: Mechanisms and Insights from Rodent Models"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-4706","authenticated-orcid":false,"given":"Milica","family":"Veljkovi\u0107","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical Faculty, University of Ni\u0161, Zoran \u0110in\u0111i\u0107 Boulevard 81, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-8592","authenticated-orcid":false,"given":"Tanja","family":"D\u017eopali\u0107","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Faculty, University of Ni\u0161, Zoran \u0110in\u0111i\u0107 Boulevard 81, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4569-1787","authenticated-orcid":false,"given":"Pavle","family":"Ran\u0111elovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Faculty, University of Ni\u0161, Zoran \u0110in\u0111i\u0107 Boulevard 81, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3294-9803","authenticated-orcid":false,"given":"Lidija","family":"Popovi\u0107 Dragonji\u0107","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Epidemiology, Medical Faculty, University of Ni\u0161, 18 000 Ni\u0161, Serbia"},{"name":"Clinic for Infectology, University Clinical Center Ni\u0161, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-0109","authenticated-orcid":false,"given":"Jelena","family":"Milenkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathological Physiology, Medical Faculty, University of Ni\u0161, Zoran \u0110in\u0111i\u0107 Boulevard 81, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-6681","authenticated-orcid":false,"given":"Ivan","family":"Ili\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical Faculty, University of Ni\u0161, Zoran \u0110in\u0111i\u0107 Boulevard 81, 18 000 Ni\u0161, Serbia"},{"name":"Clinic for Pathology, University Clinical Center Ni\u0161, 18 000 Ni\u0161, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1007\/s00213-021-05977-7","article-title":"Animal Models of Chemotherapy-Induced Cognitive Decline in Preclinical Drug Development","volume":"238","author":"John","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fernandez, H.R., Varma, A., Flowers, S.A., and Rebeck, G.W. (2020). Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer\u2019s Disease Risk Factor APOE. Cancers, 12.","DOI":"10.3390\/cancers12123842"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12075","DOI":"10.15252\/emmm.202012075","article-title":"Cellular Mechanisms and Treatments for Chemobrain: Insight from Aging and Neurodegenerative Diseases","volume":"12","author":"Nguyen","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.jpainsymman.2012.11.005","article-title":"New Approaches to Understand Cognitive Changes Associated with Chemotherapy for Non-Central Nervous System Tumors","volume":"46","author":"Nelson","year":"2013","journal-title":"J. Pain Symptom Manag."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1007\/s12035-017-0797-7","article-title":"Astaxanthin Ameliorates Doxorubicin-Induced Cognitive Impairment (Chemobrain) in Experimental Rat Model: Impact on Oxidative, Inflammatory, and Apoptotic Machineries","volume":"55","author":"Wahdan","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115391","DOI":"10.1016\/j.bbr.2024.115391","article-title":"Changes in Cognition and Astrocytic Reactivity in a Female Rodent Model of Chemotherapy-Induced Cognitive Impairment Are Variable Both Acutely and Chronically","volume":"480","author":"Haller","year":"2025","journal-title":"Behav. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrc2073","article-title":"Candidate Mechanisms for Chemotherapy-Induced Cognitive Changes","volume":"7","author":"Ahles","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s10549-010-1088-4","article-title":"Gray Matter Reduction Associated with Systemic Chemotherapy for Breast Cancer: A Prospective MRI Study","volume":"123","author":"McDonald","year":"2010","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.bbi.2012.05.007","article-title":"Frontal Gray Matter Reduction after Breast Cancer Chemotherapy and Association with Executive Symptoms: A Replication and Extension Study","volume":"30","author":"McDonald","year":"2013","journal-title":"Brain. Behav. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1200\/JCO.2007.10.8639","article-title":"Brain Structure and Function Differences in Monozygotic Twins: Possible Effects of Breast Cancer Chemotherapy","volume":"25","author":"Ferguson","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Menning, S., de Ruiter, M.B., Veltman, D.J., Boogerd, W., Oldenburg, H.S.A., Reneman, L., and Schagen, S.B. (2017). Changes in Brain Activation in Breast Cancer Patients Depend on Cognitive Domain and Treatment Type. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171724"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, S., El Jurdi, N., Thyagarajan, B., Prizment, A., and Blaes, A.H. (2024). Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063319"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xiao, S., Qin, D., Hou, X., Tian, L., Yu, Y., Zhang, R., Lyu, H., Guo, D., Chen, X.-Z., and Zhou, C. (2023). Cellular Senescence: A Double-Edged Sword in Cancer Therapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1189015"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Loganathan, T., and Doss C, G.P. (2025). Gut Microbiota and Its Influence on the Gut-Brain Axis in Comparison with Chemotherapy Patients and Cancer-Free Control Data in Breast Cancer\u2014A Computational Perspective. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0324742"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.neubiorev.2020.07.002","article-title":"The Microbiota-Gut-Brain Axis: An Emerging Therapeutic Target in Chemotherapy-Induced Cognitive Impairment","volume":"116","author":"Subramaniam","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101297","DOI":"10.1016\/j.tranon.2021.101297","article-title":"Blood and Neuroimaging Biomarkers of Cognitive Sequelae in Breast Cancer Patients throughout Chemotherapy: A Systematic Review","volume":"16","author":"Schroyen","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1177\/1073858413504465","article-title":"Glial Biology in Learning and Cognition","volume":"20","author":"Fields","year":"2014","journal-title":"Neuroscientist"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.neuron.2019.10.013","article-title":"Disruption of Oligodendrogenesis Impairs Memory Consolidation in Adult Mice","volume":"105","author":"Steadman","year":"2020","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/87565641003696775","article-title":"White Matter in Aging and Cognition: A Cross-Sectional Study of Microstructure in Adults Aged Eighteen to Eighty-Three","volume":"35","author":"Bendlin","year":"2010","journal-title":"Dev. Neuropsychol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1080\/13803395.2011.595397","article-title":"Age-Related Slowing in Cognitive Processing Speed Is Associated with Myelin Integrity in a Very Healthy Elderly Sample","volume":"33","author":"Lu","year":"2011","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ENEURO.0203-18.2018","DOI":"10.1523\/ENEURO.0203-18.2018","article-title":"Myelination of Axons Corresponds with Faster Transmission Speed in the Prefrontal Cortex of Developing Male Rats","volume":"5","author":"McDougall","year":"2018","journal-title":"eNeuro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/jbiol50","article-title":"CNS Progenitor Cells and Oligodendrocytes Are Targets of Chemotherapeutic Agents in Vitro and in Vivo","volume":"5","author":"Dietrich","year":"2006","journal-title":"J. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/jbiol69","article-title":"Systemic 5-Fluorouracil Treatment Causes a Syndrome of Delayed Myelin Destruction in the Central Nervous System","volume":"7","author":"Han","year":"2008","journal-title":"J. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10051","DOI":"10.1158\/0008-5472.CAN-10-1400","article-title":"Mathematical and Experimental Approaches to Identify and Predict the Effects of Chemotherapy on Neuroglial Precursors","volume":"70","author":"Hyrien","year":"2010","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1126\/science.1254960","article-title":"Motor Skill Learning Requires Active Central Myelination","volume":"346","author":"McKenzie","year":"2014","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.phrs.2017.01.001","article-title":"Dysregulation of Cytokine Mediated Chemotherapy Induced Cognitive Impairment","volume":"117","author":"Ren","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30324","DOI":"10.18632\/oncotarget.25718","article-title":"Doxorubicin-Induced Elevated Oxidative Stress and Neurochemical Alterations in Brain and Cognitive Decline: Protection by MESNA and Insights into Mechanisms of Chemotherapy-Induced Cognitive Impairment (\u201cchemobrain\u201d)","volume":"9","author":"Keeney","year":"2018","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, X., Hu, Y., Cao, Z., Liu, Q., and Cheng, Y. (2018). Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer\u2019s Disease, Parkinson\u2019s Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02122"},{"key":"ref_29","first-page":"5807","article-title":"Recent Progress in the Elucidation of the Mechanisms of Chemotherapy-Induced Cognitive Impairment","volume":"25","author":"Alhowail","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.tips.2016.06.007","article-title":"Targeting Oxidative Stress in Central Nervous System Disorders","volume":"37","author":"Patel","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","first-page":"363","article-title":"Cancer Treatment and Survivorship Statistics, 2019","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"a025130","DOI":"10.1101\/cshperspect.a025130","article-title":"DNA Damage, DNA Repair, Aging, and Neurodegeneration","volume":"5","author":"Maynard","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1055\/s-0030-1267852","article-title":"Chemotherapy Agents: A Primer for the Interventional Radiologist","volume":"27","author":"Mihlon","year":"2010","journal-title":"Semin. Interv. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dubey, J., Ratnakaran, N., and Koushika, S.P. (2015). Neurodegeneration and Microtubule Dynamics: Death by a Thousand Cuts. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00343"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.neuron.2011.05.001","article-title":"Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions","volume":"70","author":"Ming","year":"2011","journal-title":"Neuron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.cell.2014.01.044","article-title":"Neurogenesis in the Striatum of the Adult Human Brain","volume":"156","author":"Ernst","year":"2014","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/lio2.135","article-title":"Olfactory Epithelium: Cells, Clinical Disorders, and Insights from an Adult Stem Cell Niche","volume":"3","author":"Choi","year":"2018","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.nec.2006.10.007","article-title":"Neurogenesis after Traumatic Brain Injury","volume":"18","author":"Richardson","year":"2007","journal-title":"Neurosurg. Clin. N. Am."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s10495-010-0491-y","article-title":"Neurogenesis in the Aged and Neurodegenerative Brain","volume":"15","author":"Shruster","year":"2010","journal-title":"Apoptosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jneuroim.2015.08.012","article-title":"Neurocognitive Function, Brain-Derived Neurotrophic Factor (BDNF) and IL-6 Levels in Cancer Patients with Depression","volume":"287","author":"Jehn","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3109\/10428194.2014.915546","article-title":"Post-Chemotherapy Cognitive Impairment in Patients with B-Cell Non-Hodgkin Lymphoma: A First Comprehensive Approach to Determine Cognitive Impairments after Treatment with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone or Rituximab and Bendamustine","volume":"56","author":"Zimmer","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrn.2018.16","article-title":"Dendritic Structural Plasticity and Neuropsychiatric Disease","volume":"19","author":"Forrest","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.expneurol.2014.02.020","article-title":"Low-Doses of Cisplatin Injure Hippocampal Synapses: A Mechanism for \u201cchemo\u201d Brain?","volume":"255","author":"Andres","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbr.2016.08.039","article-title":"5-Fluorouracil Chemotherapy Upregulates Cytokines and Alters Hippocampal Dendritic Complexity in Aged Mice","volume":"316","author":"Groves","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1158\/0008-5472.CAN-14-2237","article-title":"Stem Cell Transplantation Reverses Chemotherapy-Induced Cognitive Dysfunction","volume":"75","author":"Acharya","year":"2015","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"419","DOI":"10.5607\/en.2018.27.5.419","article-title":"Chronic Treatment with Combined Chemotherapeutic Agents Affects Hippocampal Micromorphometry and Function in Mice, Independently of Neuroinflammation","volume":"27","author":"Kang","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1002\/cncr.25685","article-title":"Catechol-O-Methyltransferase Genotype Modulates Cancer Treatment-Related Cognitive Deficits in Breast Cancer Survivors","volume":"117","author":"Small","year":"2011","journal-title":"Cancer"},{"key":"ref_48","first-page":"5087","article-title":"The COMT (Rs165599) Gene Polymorphism Contributes to Chemotherapy-Induced Cognitive Impairment in Breast Cancer Patients","volume":"8","author":"Cheng","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ejcsup.2014.03.003","article-title":"Monitoring and Optimising Cognitive Function in Cancer Patients: Present Knowledge and Future Directions","volume":"12","author":"Schagen","year":"2014","journal-title":"Eur. J. Cancer Suppl."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"112534","DOI":"10.1016\/j.bbr.2020.112534","article-title":"A Mouse Model of Chemotherapy-Related Cognitive Impairments Integrating the Risk Factors of Aging and APOE4 Genotype","volume":"384","author":"Demby","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/j.1532-2149.2012.00172.x","article-title":"Paclitaxel-induced Neuropathic Pain Is Age Dependent and Devolves on Glial Response","volume":"17","author":"Baulies","year":"2013","journal-title":"Eur. J. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neurobiolaging.2016.05.014","article-title":"Age-Related Changes in the Function and Structure of the Peripheral Sensory Pathway in Mice","volume":"45","author":"Canta","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tay, N., Laakso, E.-L., Schweitzer, D., Endersby, R., Vetter, I., and Starobova, H. (2022). Chemotherapy-Induced Peripheral Neuropathy in Children and Adolescent Cancer Patients. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1015746"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1001\/jamaneurol.2018.0963","article-title":"Chemotherapy-Induced Peripheral Neuropathy in Long-Term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes","volume":"75","author":"Kandula","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/jns.12544","article-title":"Targeting Translation: A Review of Preclinical Animal Models in the Development of Treatments for Chemotherapy-induced Peripheral Neuropathy","volume":"28","author":"White","year":"2023","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/0023677215575863","article-title":"Gender Differences in a Mouse Model of Chemotherapy-Induced Neuropathic Pain","volume":"50","author":"Vaseghi","year":"2016","journal-title":"Lab. Anim."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4097\/kjae.2012.62.1.66","article-title":"Gender Differences in Paclitaxel-Induced Neuropathic Pain Behavior and Analgesic Response in Rats","volume":"62","author":"Hwang","year":"2012","journal-title":"Korean J. Anesthesiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1016\/j.lfs.2004.01.002","article-title":"Paclitaxel-Induced Neuropathic Hypersensitivity in Mice: Responses in 10 Inbred Mouse Strains","volume":"74","author":"Smith","year":"2004","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gadgil, S., Erg\u00fcn, M., Van Den Heuvel, S.A., Van Der Wal, S.E., Scheffer, G.J., and Hooijmans, C.R. (2019). A Systematic Summary and Comparison of Animal Models for Chemotherapy Induced (Peripheral) Neuropathy (CIPN). PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221787"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Currie, G.L., Angel-Scott, H.N., Colvin, L., Cramond, F., Hair, K., Khandoker, L., Liao, J., Macleod, M., McCann, S.K., and Morland, R. (2019). Animal Models of Chemotherapy-Induced Peripheral Neuropathy: A Machine-Assisted Systematic Review and Meta-Analysis. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000243"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mohammad, A.S., Adkins, C.E., Shah, N., Aljammal, R., Griffith, J.I.G., Tallman, R.M., Jarrell, K.L., and Lockman, P.R. (2018). Permeability Changes and Effect of Chemotherapy in Brain Adjacent to Tumor in an Experimental Model of Metastatic Brain Tumor from Breast Cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5115-x"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Otto, L.D., Russart, K.L.G., Kulkarni, P., McTigue, D.M., Ferris, C.F., and Pyter, L.M. (2022). Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence from In Vivo Diffusion Weighted Imaging. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.798704"},{"key":"ref_63","first-page":"25","article-title":"Cisplatin\u2014An Overview of Its Efficiency and Toxicity","volume":"25","author":"Stojanovic","year":"2023","journal-title":"Facta Univ. Ser. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1021\/acschemneuro.1c00338","article-title":"Neuropathological Effects of Chemotherapeutic Drugs","volume":"12","author":"Umfress","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Was, H., Borkowska, A., Bagues, A., Tu, L., Liu, J.Y.H., Lu, Z., Rudd, J.A., Nurgali, K., and Abalo, R. (2022). Mechanisms of Chemotherapy-Induced Neurotoxicity. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.750507"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1007\/s11357-025-01560-6","article-title":"Cisplatin and Methotrexate Induce Brain Microvascular Endothelial and Microglial Senescence in Mouse Models of Chemotherapy-Associated Cognitive Impairment","volume":"47","author":"Csik","year":"2025","journal-title":"GeroScience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1007\/s12035-018-1224-4","article-title":"Chemotherapy-Induced Cognitive Impairment Is Associated with Cytokine Dysregulation and Disruptions in Neuroplasticity","volume":"56","author":"Shi","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vichaya, E.G., Chiu, G.S., Krukowski, K., Lacourt, T.E., Kavelaars, A., Dantzer, R., Heijnen, C.J., and Walker, A.K. (2015). Mechanisms of Chemotherapy-Induced Behavioral Toxicities. Front. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00131"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.neuron.2019.04.032","article-title":"Loss of Adaptive Myelination Contributes to Methotrexate Chemotherapy-Related Cognitive Impairment","volume":"103","author":"Geraghty","year":"2019","journal-title":"Neuron"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lacourt, T.E., Vichaya, E.G., Chiu, G.S., Dantzer, R., and Heijnen, C.J. (2018). The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-Adaptive Energy Expenditure. Front. Behav. Neurosci., 12.","DOI":"10.3389\/fnbeh.2018.00078"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Brandolini, L., d\u2019Angelo, M., Antonosante, A., Allegretti, M., and Cimini, A. (2019). Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122904"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1158\/1078-0432.CCR-11-2000","article-title":"Impaired Cognitive Function and Hippocampal Neurogenesis Following Cancer Chemotherapy","volume":"18","author":"Christie","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.bbr.2007.08.004","article-title":"Long-Lasting Suppression of Hippocampal Cell Proliferation and Impaired Cognitive Performance by Methotrexate in the Rat","volume":"186","author":"Seigers","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cell.2018.10.049","article-title":"Methotrexate Chemotherapy Induces Persistent Tri-Glial Dysregulation That Underlies Chemotherapy-Related Cognitive Impairment","volume":"176","author":"Gibson","year":"2019","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1096\/fj.12-214643","article-title":"Prevention of Paclitaxel-Induced Peripheral Neuropathy by Lithium Pretreatment","volume":"26","author":"Mo","year":"2012","journal-title":"FASEB J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bbi.2022.12.004","article-title":"Microglia Are Implicated in the Development of Paclitaxel Chemotherapy-Associated Cognitive Impairment in Female Mice","volume":"108","author":"Grant","year":"2023","journal-title":"Brain. Behav. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s00213-013-3301-8","article-title":"The Impact of Sustained and Intermittent Docetaxel Chemotherapy Regimens on Cognition and Neural Morphology in Healthy Mice","volume":"231","author":"Fardell","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"838","DOI":"10.2174\/1570159X18666200221113842","article-title":"An Overview on Chemotherapy-Induced Cognitive Impairment and Potential Role of Antidepressants","volume":"18","author":"Das","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e13832","DOI":"10.1111\/acel.13832","article-title":"Accelerated Cerebromicrovascular Senescence Contributes to Cognitive Decline in a Mouse Model of Paclitaxel (Taxol)-Induced Chemobrain","volume":"22","author":"Ahire","year":"2023","journal-title":"Aging Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.neuropharm.2018.02.013","article-title":"Physical Exercise Prevents Cognitive Impairment by Enhancing Hippocampal Neuroplasticity and Mitochondrial Function in Doxorubicin-Induced Chemobrain","volume":"133","author":"Park","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1460-9568.2008.06325.x","article-title":"5-Fluorouracil Chemotherapy Affects Spatial Working Memory and Newborn Neurons in the Adult Rat Hippocampus","volume":"28","author":"Mustafa","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.nlm.2017.08.001","article-title":"The Chemotherapeutic Agent Paclitaxel Selectively Impairs Reversal Learning While Sparing Prior Learning, New Learning and Episodic Memory","volume":"144","author":"Carey","year":"2017","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1007\/s13311-021-01092-9","article-title":"Donepezil Protects Against Doxorubicin-Induced Chemobrain in Rats via Attenuation of Inflammation and Oxidative Stress without Interfering with Doxorubicin Efficacy","volume":"18","author":"Ongnok","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Zhou, W., Kavelaars, A., and Heijnen, C.J. (2016). Metformin Prevents Cisplatin-Induced Cognitive Impairment and Brain Damage in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151890"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.4172\/Neuropsychiatry.1000565","article-title":"Chemobrain as a Product of Growing Success in Chemotherapy\u2014Focus on Glia as Both a Victim and a Cure","volume":"9","author":"Walczak","year":"2019","journal-title":"Neuropsychiatry"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1158\/0008-5472.CAN-16-1817","article-title":"Pifithrin-\u03bc Prevents Cisplatin-Induced Chemobrain by Preserving Neuronal Mitochondrial Function","volume":"77","author":"Chiu","year":"2017","journal-title":"Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejphar.2016.08.003","article-title":"Edaravone Alleviates Cisplatin-Induced Neurobehavioral Deficits via Modulation of Oxidative Stress and Inflammatory Mediators in the Rat Hippocampus","volume":"791","author":"Jangra","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.toxlet.2006.05.005","article-title":"Oxidative Stress Induced by Methotrexate Alone and in the Presence of Methanol in Discrete Regions of the Rodent Brain, Retina and Optic Nerve","volume":"165","author":"Rajamani","year":"2006","journal-title":"Toxicol. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.nbd.2018.03.006","article-title":"Resveratrol, a Natural Polyphenol, Prevents Chemotherapy-Induced Cognitive Impairment: Involvement of Cytokine Modulation and Neuroprotection","volume":"114","author":"Shi","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.bbr.2019.01.007","article-title":"5-Fluorouracil Impairs Attention and Dopamine Release in Rats","volume":"362","author":"Jarmolowicz","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.pain.2006.01.037","article-title":"Studies of Peripheral Sensory Nerves in Paclitaxel-Induced Painful Peripheral Neuropathy: Evidence for Mitochondrial Dysfunction","volume":"122","author":"Flatters","year":"2006","journal-title":"Pain"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s12609-017-0245-8","article-title":"Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics","volume":"9","author":"Lacourt","year":"2017","journal-title":"Curr. Breast Cancer Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainresbull.2012.07.003","article-title":"Acute Treatment with Methotrexate Induces Hippocampal Dysfunction in a Mouse Model of Breast Cancer","volume":"89","author":"Yang","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.bbi.2015.06.003","article-title":"MAPK Signaling Downstream to TLR4 Contributes to Paclitaxel-Induced Peripheral Neuropathy","volume":"49","author":"Li","year":"2015","journal-title":"Brain. Behav. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"145239","DOI":"10.1016\/j.gene.2020.145239","article-title":"Silymarin Alleviates Docetaxel-Induced Central and Peripheral Neurotoxicity by Reducing Oxidative Stress, Inflammation and Apoptosis in Rats","volume":"769","author":"Kucukler","year":"2021","journal-title":"Gene"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"17400","DOI":"10.1038\/s41598-018-35919-x","article-title":"Cisplatin Treatment Induces Attention Deficits and Impairs Synaptic Integrity in the Prefrontal Cortex in Mice","volume":"8","author":"Huo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainres.2017.07.003","article-title":"Acute Treatment with Doxorubicin Affects Glutamate Neurotransmission in the Mouse Frontal Cortex and Hippocampus","volume":"1672","author":"Thomas","year":"2017","journal-title":"Brain Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"106","DOI":"10.5306\/wjco.v7.i1.106","article-title":"Role of Copper Transporters in Platinum Resistance","volume":"7","author":"Kilari","year":"2016","journal-title":"World J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s002800050391","article-title":"Difference in CDDP Penetration into CSF between Selective Intraarterial Chemotherapy in Patients with Malignant Glioma and Intravenous or Intracarotid Administration in Patients with Metastatic Brain Tumor","volume":"37","author":"Nakagawa","year":"1996","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bbr.2009.11.017","article-title":"Fluoxetine Improves the Memory Deficits Caused by the Chemotherapy Agent 5-Fluorouracil","volume":"208","author":"ELBeltagy","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Lyons, L., ElBeltagy, M., Bennett, G., and Wigmore, P. (2012). Fluoxetine Counteracts the Cognitive and Cellular Effects of 5-Fluorouracil in the Rat Hippocampus by a Mechanism of Prevention Rather than Recovery. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030010"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1254\/jjp.48.499","article-title":"Effect of Methotrexate on Local Cerebral Blood Flow in Conscious Rats","volume":"48","author":"Mizusawa","year":"1988","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_103","first-page":"202","article-title":"Fluvoxamine Alleviates Paclitaxel-Induced Neurotoxicity","volume":"4","author":"Tanimukai","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1080\/09168451.2020.1722057","article-title":"Polydatin Ameliorates Chemotherapy-Induced Cognitive Impairment (Chemobrain) by Inhibiting Oxidative Stress, Inflammatory Response, and Apoptosis in Rats","volume":"84","author":"Tong","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_105","first-page":"9660","article-title":"Ameliorative Effect of Metformin on Cyclophosphamide-Induced Memory Impairment in Mice","volume":"23","author":"Alhowail","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3941840","DOI":"10.1155\/2018\/3941840","article-title":"Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory","volume":"2018","author":"Li","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e1185","DOI":"10.1038\/tp.2017.149","article-title":"A Novel Preventive Therapy for Paclitaxel-Induced Cognitive Deficits: Preclinical Evidence from C57BL\/6 Mice","volume":"7","author":"Huehnchen","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"11667","DOI":"10.1038\/s41598-017-12054-7","article-title":"The Cancer Chemotherapeutic Agent Paclitaxel (Taxol) Reduces Hippocampal Neurogenesis via down-Regulation of Vesicular Zinc","volume":"7","author":"Lee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.lfs.2013.05.006","article-title":"The Short and Long Term Effects of Docetaxel Chemotherapy on Rodent Object Recognition and Spatial Reference Memory","volume":"93","author":"Fardell","year":"2013","journal-title":"Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.bbr.2015.04.044","article-title":"Long-Term Cognitive Dysfunction in the Rat Following Docetaxel Treatment Is Ameliorated by the Phosphodiesterase-4 Inhibitor, Rolipram","volume":"290","author":"Callaghan","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00213-014-3636-9","article-title":"Cognitive Impact of Cytotoxic Agents in Mice","volume":"232","author":"Seigers","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1615\/JEnvironPatholToxicolOncol.2019028294","article-title":"Rutin Protects against Doxorubicin-Induced Cognitive Dysfunction While Retaining the Anticancer Potential of Dox in a Murine Model of N-Methyl-N-Nitrosourea\u2014Induced Mammary Carcinoma","volume":"38","author":"Ramalingayya","year":"2019","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.freeradbiomed.2016.11.046","article-title":"Cisplatin-Induced Mitochondrial Dysfunction Is Associated with Impaired Cognitive Function in Rats","volume":"102","author":"Lomeli","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.nlm.2010.01.006","article-title":"Cyclophosphamide Impairs Hippocampus-Dependent Learning and Memory in Adult Mice: Possible Involvement of Hippocampal Neurogenesis in Chemotherapy-Induced Memory Deficits","volume":"93","author":"Yang","year":"2010","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.pbb.2009.09.001","article-title":"Systemic Administration of Doxorubicin Impairs Aversively Motivated Memory in Rats","volume":"94","author":"Liedke","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12031-015-0535-4","article-title":"Microtubule Dynamicity Is More Important than Stability in Memory Formation: An In Vivo Study","volume":"56","author":"Atarod","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1097\/j.pain.0000000000001233","article-title":"Cognitive Impairment in a Rat Model of Neuropathic Pain: Role of Hippocampal Microtubule Stability","volume":"159","author":"You","year":"2018","journal-title":"Pain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"108334","DOI":"10.1016\/j.neuropharm.2020.108334","article-title":"Caffeic Acid Phenethyl Ester Counteracts Doxorubicin-Induced Chemobrain in Sprague-Dawley Rats: Emphasis on the Modulation of Oxidative Stress and Neuroinflammation","volume":"181","author":"Ali","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.neuroscience.2010.11.007","article-title":"Doxorubicin-Induced Central Nervous System Toxicity and Protection by Xanthone Derivative of Garcinia Mangostana","volume":"175","author":"Tangpong","year":"2011","journal-title":"Neuroscience"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.freeradbiomed.2020.07.018","article-title":"Protective Effects of Diallyl Trisulfide (DATS) against Doxorubicin-Induced Inflammation and Oxidative Stress in the Brain of Rats","volume":"160","author":"Leung","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s12031-015-0547-0","article-title":"Naringin Abrogates Cisplatin-Induced Cognitive Deficits and Cholinergic Dysfunction Through the Down-Regulation of AChE Expression and iNOS Signaling Pathways in Hippocampus of Aged Rats","volume":"56","author":"Chtourou","year":"2015","journal-title":"J. Mol. Neurosci. MN"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bbr.2016.11.013","article-title":"Systemic Cisplatin Exposure during Infancy and Adolescence Causes Impaired Cognitive Function in Adulthood","volume":"319","author":"John","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"116867","DOI":"10.1016\/j.lfs.2019.116867","article-title":"Nerolidol Ameliorates Cyclophosphamide-Induced Oxidative Stress, Neuroinflammation and Cognitive Dysfunction: Plausible Role of Nrf2 and NF-\u03baB","volume":"236","author":"Iqubal","year":"2019","journal-title":"Life Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/jmf.2006.9.261","article-title":"Prophylactic Action of Linseed (Linum usitatissimum) Oil against Cyclophosphamide-Induced Oxidative Stress in Mouse Brain","volume":"9","author":"Bhatia","year":"2006","journal-title":"J. Med. Food"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3109\/19390211.2015.1103827","article-title":"Gallic Acid Ameliorates Cyclophosphamide-Induced Neurotoxicity in Wistar Rats Through Free Radical Scavenging Activity and Improvement in Antioxidant Defense System","volume":"13","author":"Oyagbemi","year":"2016","journal-title":"J. Diet. Suppl."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1200\/JCO.2016.68.5826","article-title":"Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared with Age-Matched Controls: An Analysis from a Nationwide, Multicenter, Prospective Longitudinal Study","volume":"35","author":"Janelsins","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wu, L., Guo, D., Liu, Q., Gao, F., Wang, X., Song, X., Wang, F., and Zhan, R.-Z. (2017). Abnormal Development of Dendrites in Adult-Born Rat Hippocampal Granule Cells Induced by Cyclophosphamide. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00171"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.pbb.2009.10.008","article-title":"Systemic Methotrexate Induces Spatial Memory Deficits and Depletes Cerebrospinal Fluid Folate in Rats","volume":"94","author":"Li","year":"2010","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.bbr.2011.09.013","article-title":"Preserved Learning and Memory in Mice Following Chemotherapy: 5-Fluorouracil and Doxorubicin Single Agent Treatment, Doxorubicin-Cyclophosphamide Combination Treatment","volume":"226","author":"Fremouw","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/toxsci\/kfz213","article-title":"Early Effects of Cyclophosphamide, Methotrexate, and 5-Fluorouracil on Neuronal Morphology and Hippocampal-Dependent Behavior in a Murine Model","volume":"173","author":"Anderson","year":"2020","journal-title":"Toxicol. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bbi.2013.07.175","article-title":"Dysregulation in Myelination Mediated by Persistent Neuroinflammation: Possible Mechanisms in Chemotherapy-Related Cognitive Impairment","volume":"35","author":"Briones","year":"2014","journal-title":"Brain. Behav. Immun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/br.2020.1377","article-title":"Neuroprotective Effect of MulminaTM against Chemotherapy-Induced Cognitive Decline in Normal Mice","volume":"14","author":"Kinra","year":"2021","journal-title":"Biomed. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2008.08.060","article-title":"A Novel Electrophysiological Model of Chemotherapy-Induced Cognitive Impairments in Mice","volume":"157","author":"Gandal","year":"2008","journal-title":"Neuroscience"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00213-011-2310-8","article-title":"Effects of Repeated Administration of Chemotherapeutic Agents Tamoxifen, Methotrexate, and 5-Fluorouracil on the Acquisition and Retention of a Learned Response in Mice","volume":"217","author":"Walker","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.neuropharm.2011.07.013","article-title":"Donepezil Reduces Cognitive Impairment Associated with Anti-Cancer Drugs in a Mouse Model","volume":"61","author":"Winocur","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","article-title":"A Blood\u2013Brain Barrier Overview on Structure, Function, Impairment, and Biomarkers of Integrity","volume":"17","author":"Kadry","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The Blood\u2013Brain Barrier: An Overview","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.cell.2015.10.067","article-title":"Establishment and Dysfunction of the Blood-Brain Barrier","volume":"163","author":"Zhao","year":"2015","journal-title":"Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/bpa.12152","article-title":"The Pericyte: A Forgotten Cell Type with Important Implications for A Lzheimer\u2019s Disease?","volume":"24","author":"Winkler","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1007\/s11064-015-1581-6","article-title":"The Glymphatic System: A Beginner\u2019s Guide","volume":"40","author":"Jessen","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The Blood-Brain Barrier: Structure, Regulation, and Drug Delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"120693","DOI":"10.1016\/j.jns.2023.120693","article-title":"Cyclophosphamide for Severe Acute Forms of Central Nervous System Inflammatory Disorders","volume":"451","author":"Osen","year":"2023","journal-title":"J. Neurol. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.tins.2018.05.001","article-title":"A Call for a Neuroscience Approach to Cancer-Related Cognitive Impairment","volume":"41","author":"Horowitz","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/pon.1878","article-title":"Development of CBT for Chemotherapy-Related Cognitive Change: Results of a Waitlist Control Trial","volume":"21","author":"Ferguson","year":"2012","journal-title":"Psycho-Oncology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.clbc.2013.02.004","article-title":"Cognitive Training for Improving Executive Function in Chemotherapy-Treated Breast Cancer Survivors","volume":"13","author":"Kesler","year":"2013","journal-title":"Clin. Breast Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1177\/0898010114539191","article-title":"Complementary and Alternative Medicine Therapies as Symptom Management Strategies for the Late Effects of Breast Cancer Treatment","volume":"33","author":"Henneghan","year":"2015","journal-title":"J. Holist. Nurs."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1097\/NCC.0000000000000349","article-title":"Interventions for Cognitive Deficits in Breast Cancer Survivors Treated with Chemotherapy","volume":"40","author":"Vance","year":"2017","journal-title":"Cancer Nurs."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00213-011-2466-2","article-title":"Cognitive Impairments Caused by Oxaliplatin and 5-Fluorouracil Chemotherapy Are Ameliorated by Physical Activity","volume":"220","author":"Fardell","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1007\/s00213-013-3394-0","article-title":"Physical Exercise Prevents Suppression of Hippocampal Neurogenesis and Reduces Cognitive Impairment in Chemotherapy-Treated Rats","volume":"231","author":"Winocur","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1037\/bne0000155","article-title":"Environmental Enrichment Protects against Cognitive Impairment Following Chemotherapy in an Animal Model","volume":"130","author":"Winocur","year":"2016","journal-title":"Behav. Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1007\/s12035-018-1283-6","article-title":"Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation","volume":"56","author":"Doorduin","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.tics.2013.08.001","article-title":"Bridging Animal and Human Models of Exercise-Induced Brain Plasticity","volume":"17","author":"Voss","year":"2013","journal-title":"Trends Cogn. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.tins.2010.09.003","article-title":"When Neurogenesis Encounters Aging and Disease","volume":"33","author":"Lazarov","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1089\/neu.2014.3328","article-title":"Environmental Enrichment as a Viable Neurorehabilitation Strategy for Experimental Traumatic Brain Injury","volume":"31","author":"Bondi","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/j.1460-9568.2011.07614.x","article-title":"Neurogenesis and Affective Disorders","volume":"33","author":"Samuels","year":"2011","journal-title":"Eur. J. Neurosci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/pon.742","article-title":"The Relationship of APOE Genotype to Neuropsychological Performance in Long-Term Cancer Survivors Treated with Standard Dose Chemotherapy","volume":"12","author":"Ahles","year":"2003","journal-title":"Psychooncology."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1200\/JCO.18.00140","article-title":"Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living with Cancer Study","volume":"36","author":"Mandelblatt","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.bbr.2011.08.006","article-title":"Persistent Cognitive Deficits, Induced by Intrathecal Methotrexate, Are Associated with Elevated CSF Concentrations of Excitotoxic Glutamate Analogs and Can Be Reversed by an NMDA Antagonist","volume":"225","author":"Vijayanathan","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.neulet.2016.11.028","article-title":"Neo-Adjuvant Chemotherapy with Cisplatin Induces Low Expression of NMDA Receptors and Postoperative Cognitive Impairment","volume":"637","author":"Cheng","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.coph.2014.11.002","article-title":"AMPA Receptor Potentiators: From Drug Design to Cognitive Enhancement","volume":"20","author":"Partin","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"ENEURO.0133-15.2016","DOI":"10.1523\/ENEURO.0133-15.2016","article-title":"Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex","volume":"3","author":"Phoumthipphavong","year":"2016","journal-title":"eNeuro"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"659","DOI":"10.12688\/f1000research.14344.1","article-title":"Ketamine and Rapid-Acting Antidepressants: A New Era in the Battle against Depression and Suicide","volume":"7","author":"Duman","year":"2018","journal-title":"F1000Research"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bbr.2017.07.021","article-title":"Ibudilast Reduces Oxaliplatin-Induced Tactile Allodynia and Cognitive Impairments in Rats","volume":"334","author":"Johnston","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"17957","DOI":"10.1073\/pnas.0908563106","article-title":"Inhibition of Protein Kinase C Signaling Protects Prefrontal Cortex Dendritic Spines and Cognition from the Effects of Chronic Stress","volume":"106","author":"Hains","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Brudvig, J.J., and Weimer, J.M. (2015). X MARCKS the Spot: Myristoylated Alanine-Rich C Kinase Substrate in Neuronal Function and Disease. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00407"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00213-010-2122-2","article-title":"Fluoxetine Reverses the Memory Impairment and Reduction in Proliferation and Survival of Hippocampal Cells Caused by Methotrexate Chemotherapy","volume":"215","author":"Lyons","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12974-015-0366-9","article-title":"Colony-Stimulating Factor 1 Receptor Inhibition Prevents Microglial Plaque Association and Improves Cognition in 3xTg-AD Mice","volume":"12","author":"Dagher","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.clinbiochem.2019.04.001","article-title":"Neuro-Inflammation and Anti-Inflammatory Treatment Options for Alzheimer\u2019s Disease","volume":"72","author":"Ozben","year":"2019","journal-title":"Clin. Biochem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00011-018-1185-0","article-title":"A Comprehensive Review on the Treatment Approaches of Multiple Sclerosis: Currently and in the Future","volume":"68","author":"Gholamzad","year":"2019","journal-title":"Inflamm. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1001\/jamaneurol.2019.3762","article-title":"Minocycline at 2 Different Dosages vs Placebo for Patients with Mild Alzheimer Disease: A Randomized Clinical Trial","volume":"77","author":"Howard","year":"2020","journal-title":"JAMA Neurol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/7\/750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:41:19Z","timestamp":1784191279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/7\/750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":170,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["brainsci16070750"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16070750","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]}}}