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Chemotherapy-induced cognitive impairment

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https://www.readbyqxmd.com/read/28763058/a-novel-preventive-therapy-for-paclitaxel-induced-cognitive-deficits-preclinical-evidence-from-c57bl-6-mice
#1
P Huehnchen, W Boehmerle, A Springer, D Freyer, M Endres
Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg(-1) paclitaxel (PTX), mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed visuo-spatial memory impairments, and we measured peak PTX concentrations in the hippocampus of 230 nm l(-1), which was sevenfold higher compared with the neocortex...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28739131/ibudilast-reduces-oxaliplatin-induced-tactile-allodynia-and-cognitive-impairments-in-rats
#2
Ian N Johnston, Manuela Tan, Jacob Cao, Antigone Matsos, Daniel R L Forrest, Emily Si, Joanna E Fardell, Mark R Hutchinson
Chemotherapy can cause serious neurotoxic side effects, such as painful peripheral neuropathies and disabling cognitive impairments. Four experiments examined whether Ibudilast, a clinically approved neuroimmune therapy, would reduce tactile allodynia and memory impairments caused by oxaliplatin in laboratory rats. Rats received an intraperitoneal injection of oxaliplatin (6mg/kg i.p.) or vehicle and were assessed for tactile allodynia 3 or 5days after injection, memory impairments in the novel object and novel location recognition tests 10-12days after injection, and fear conditioning 14days after injection...
July 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28700628/asiatic-acid-protects-against-cognitive-deficits-and-reductions-in-cell-proliferation-and-survival-in-the-rat-hippocampus-caused-by-5-fluorouracil-chemotherapy
#3
Pornthip Chaisawang, Apiwat Sirichoat, Wunnee Chaijaroonkhanarak, Wanassanun Pannangrong, Bungorn Sripanidkulchai, Peter Wigmore, Jariya Umka Welbat
The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogenesis in the hippocampus and memory deficits induced by valproic acid (VPA). In the present study, we investigated the preventive effects of AA on the deficits in spatial working memory and cell proliferation and survival caused by 5-FU chemotherapy in a rat model...
2017: PloS One
https://www.readbyqxmd.com/read/28699673/combined-intravitreal-methotrexate-and-immunochemotherapy-followed-by-reduced-dose-whole-brain-radiotherapy-for-newly-diagnosed-b-cell-primary-intraocular-lymphoma
#4
Toshikatu Kaburaki, Kazuki Taoka, Junko Matsuda, Hideomi Yamashita, Izuru Matsuda, Hideki Tsuji, Rie Tanaka, Kumi Nakazaki, Fumihiko Nakamura, Kohei Kamiya, Mineo Kurokawa, Kuni Ohtomo, Makoto Aihara
Primary intraocular lymphoma (IOL) has a propensity for central nervous system (CNS) relapse within 2 years of initial diagnosis, affecting clinical outcome. To reduce CNS relapse, we performed the combination treatment protocols of intravitreal methotrexate injections, methotrexate-based systemic induction chemotherapy and consolidation high-dose cytarabine and reduced-dose whole brain radiation therapy (rdWBRT, 23·4 Gy) for B-cell primary IOL with or without newly diagnosed CNS involvement. All patients underwent longitudinal brain magnetic resonance imaging (MRI) and cognitive assessment for evaluation of treatment-induced leucoencephalopathy...
July 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28435392/a-systemic-literature-review-of-neuroimaging-studies-in-women-with-breast-cancer-treated-with-adjuvant-chemotherapy
#5
REVIEW
Paulina Andryszak, Monika Wiłkość, Paweł Izdebski, Bogdan Żurawski
Chemotherapy-induced cognitive deficits in patients with breast cancer, predominantly in attention and verbal memory, have been observed in numerous studies. These neuropsychological findings are corroborated by the results of neuroimaging studies. The aim of this paper was to survey the reports on cerebral structural and functional alterations in women with breast cancer treated with chemotherapy (CTx). First, we discuss the host-related and disease-related mechanisms underlying cognitive impairment after CTx...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28408800/rutin-protects-against-neuronal-damage-in-vitro-and-ameliorates-doxorubicin-induced-memory-deficits-in-vivo-in-wistar-rats
#6
Grandhi Venkata Ramalingayya, Sri Pragnya Cheruku, Pawan G Nayak, Anoop Kishore, Rekha Shenoy, Chamallamudi Mallikarjuna Rao, Nandakumar Krishnadas
Doxorubicin (DOX) is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors' quality of life. The study objective was to evaluate rutin (RUT) for its neuroprotective effect against DOX in human neuroblastoma (IMR32) cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28397504/-chemotherapy-related-cognitive-impairment-in-patients-with-hodgkin-lymphoma-pathophysiology-and-risk-factors
#7
D Fayette, Ľ Gahérová, H Móciková, J Marková, T Kozák, J Horáček
BACKGROUND: Cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life. CRCI affects patients of all ages. The impairment of cognitive function in connection with chemotherapy is usually mild, but an event. relationship with dementia remains to be confirmed. Chemotherapy in combination with radiotherapy in Hodgkin lymphoma can cure 80-90% of patients...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28377717/biomarkers-associated-with-cognitive-impairment-in-treated-cancer-patients-potential-predisposition-and-risk-factors
#8
REVIEW
Hélène Castel, Angeline Denouel, Marie Lange, Marie-Christine Tonon, Martine Dubois, Florence Joly
Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28359881/ku32-prevents-5-fluorouracil-induced-cognitive-impairment
#9
Michael J Sofis, David P Jarmolowicz, Sam V Kaplan, Rachel C Gehringer, Shea M Lemley, Gaurav Garg, Brian S Blagg, Michael A Johnson
Chemotherapy induced cognitive impairment (i.e. chemobrain) involves acute and long-term deficits in memory, executive function, and processing speed. Animal studies investigating these cognitive deficits have had mixed results, potentially due to variability in the complexity of behavioral tasks across experiments. Further, common chemotherapy treatments such as 5-fluorouracil (5-FU) break down myelin integrity corresponding to hippocampal neurodegenerative deficits and mitochondrial dysfunction. There is little evidence, however, of pharmacological treatments that may target mitochondrial dysfunction...
June 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28327626/altered-resting-state-hippocampal-functional-networks-associated-with-chemotherapy-induced-prospective-memory-impairment-in-breast-cancer-survivors
#10
Huaidong Cheng, Wen Li, Liang Gong, Han Xuan, Zhonglian Huang, Hong Zhao, Long Sheng Wang, Kai Wang
In this study, we aimed to investigate the intrinsic hippocampal functional connectivity (FC) network and its relationship with prospective memory in patients with breast cancer suffering from chemotherapy-induced cognitive impairment (CICI). Thirty-four breast cancer patients before and after adjuvant chemotherapy (CB and CC, respectively) and 31 age- and education-matched cognitively normal (CN) women were recruited and subjected to a prospective memory task and a resting-state functional magnetic resonance imaging scan...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108946/in-vivo-neuroimaging-and-behavioral-correlates-in-a-rat-model-of-chemotherapy-induced-cognitive-dysfunction
#11
Robert L Barry, Nellie E Byun, M Noor Tantawy, Chase A Mackey, George H Wilson, Adam J Stark, Michael P Flom, Laura C Gee, C Chad Quarles
Adjuvant chemotherapy has been used for decades to treat cancer, and it is well known that disruptions in cognitive function and memory are common chemotherapeutic adverse effects. However, studies using neuropsychological metrics have also reported group differences in cognitive function and memory before or without chemotherapy, suggesting that complex factors obscure the true etiology of chemotherapy-induced cognitive dysfunction (CICD) in humans. Therefore, to better understand possible mechanisms of CICD, we explored the effects of CICD in rats through cognition testing using novel object recognition (NOR) and contextual fear conditioning (CFC), and through metabolic neuroimaging via [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)...
January 20, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28063894/dysregulation-of-cytokine-mediated-chemotherapy-induced-cognitive-impairment
#12
REVIEW
Xiaojia Ren, Daret K St Clair, D Allan Butterfield
One of the major complaints patients who survive cancer often make is chemotherapy induced cognitive impairment (CICI), which survivors often call "chemo brain." CICI is a side effect of chemotherapy due to the cytotoxicity and neurotoxicity of anti-cancer drugs causing structural and functional changes in brain, even when drugs that do not cross the blood brain barrier (BBB) are used. Diminished cognitive functions including diminution of learning and memory, concentration and attention, processing speed and executive functions that reduce quality of life and ability to work are common signs and symptoms of CICI...
March 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27992857/tfeb-ameliorates-the-impairment-of-the-autophagy-lysosome-pathway-in-neurons-induced-by-doxorubicin
#13
Jose Felix Moruno-Manchon, Ndidi-Ese Uzor, Shelli R Kesler, Jeffrey S Wefel, Debra M Townley, Archana Sidalaghatta Nagaraja, Sunila Pradeep, Lingegowda S Mangala, Anil K Sood, Andrey S Tsvetkov
Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated liposomal doxorubicin exhibited autophagosomes, often with mitochondria, lipofuscin, and lipid droplets...
December 16, 2016: Aging
https://www.readbyqxmd.com/read/27933449/clearing-the-fog-a-review-of-the-effects-of-dietary-omega-3-fatty-acids-and-added-sugars-on-chemotherapy-induced-cognitive-deficits
#14
REVIEW
Tonya S Orchard, Monica M Gaudier-Diaz, Kellie R Weinhold, A Courtney DeVries
Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis...
February 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27908784/cisplatin-induced-mitochondrial-dysfunction-is-associated-with-impaired-cognitive-function-in-rats
#15
Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSCs). We also assessed the protective effects of the antioxidant, N-acetylcysteine in mitigating these damages...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908748/the-chemotherapeutic-agent-paclitaxel-selectively-impairs-learning-while-sparing-source-memory-and-spatial-memory
#16
Alexandra E Smith, Richard A Slivicki, Andrea G Hohmann, Jonathon D Crystal
Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27904710/the-comt-rs165599-gene-polymorphism-contributes-to-chemotherapy-induced-cognitive-impairment-in-breast-cancer-patients
#17
Huaidong Cheng, Wen Li, Chen Gan, Bo Zhang, Qianqian Jia, Kai Wang
The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27879267/pifithrin-%C3%AE-prevents-cisplatin-induced-chemobrain-by-preserving-neuronal-mitochondrial-function
#18
Gabriel S Chiu, Magdalena A Maj, Sahar Rizvi, Robert Dantzer, Elisabeth G Vichaya, Geoffroy Laumet, Annemieke Kavelaars, Cobi J Heijnen
Cognitive impairment, termed chemobrain, is a common neurotoxicity associated with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy-induced cognitive impairment (CICI), we explored the efficacy of administering the small-molecule pifithrin (PFT)-μ, an inhibitor of mitochondrial p53 accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin ± PFT-μ for two 5-day cycles were assessed for cognitive function using novel object/place recognition and alternation in a Y-maze...
February 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27851909/systemic-cisplatin-exposure-during-infancy-and-adolescence-causes-impaired-cognitive-function-in-adulthood
#19
Tami John, Naomi Lomeli, Daniela A Bota
Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown...
February 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27845242/neo-adjuvant-chemotherapy-with-cisplatin-induces-low-expression-of-nmda-receptors-and-postoperative-cognitive-impairment
#20
Jing Cheng, Xiaoqing Liu, Longhui Cao, Tianhua Zhang, Huiting Li, Wenqian Lin
Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline...
January 10, 2017: Neuroscience Letters
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