Rationale Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person’s day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies. Objectives A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain. Results Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent. Conclusion Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals.

Background : Virgin coconut oil (VCO) has been identified as a potential cognitive strengthener associated with Alzheimer’s disease (AD). It contains medium chain fatty acids (MCFA) which are absorbed and easily metabolized by the liver to form ketone bodies. Ketone bodies are converted to acetyl Co-A in the brain which then enters the citric acid cycle to provide ATP and also serves as precursors of acetylcholine in neurons. Sunflower oil (SO) contains poly unsaturated fatty acids which has both anti-inflammatory and neuroprotective actions. To compare the neuroprotective effects of VCO and SO on biochemical parameters involved in the cognitive dysfunction induced by colchicine through intracerebroventricular (i.c.v) route.To assess the role of polyphenols and MCFA present in VCO in preventing oxidative stress and its influence on in neuroprotection and memory enhancement. Methods: In the present study, we induced dementia through i.c.v injection of colchicine after giving the diet enriched VCO and SO in rats for 60 days. Rats were sacrificed on the 22nd day after the administration of colchicine. Behavioral parameters were assessed during the study period and biochemical estimations were performed using frontal cortex and hippocampus isolated from rat brain. Results: From the memory and learning tests by Morris water maze, VCO treated group performed better than SO treated rats. VCO reversed the antagonistic effects induced by colchicine by decreasing the acetylcholinesterase and malondialdehyde levels and increasing the levels of catalase and superoxide dismutase. SO only reduced malondialdehyde levels in cortex and hippocampus. Conclusion: The results demonstrated potential beneficiary effects of VCO in the cognitive dysfunction induced by colchicine by enhancing acetylcholine levels in the frontal cortex and hippocampus and also by reducing oxidative stress induced by physiological oxidants.

The post-treatment status of breast cancer survivors has become a concern because of the toxicity induced by chemotherapeutic agents in the brain tissues resulting in cognitive deficits, which is generally referred as chemobrain. The aim of this study was to assess the effect of a proprietary ayurvedic formulation Mulmina Mango against chemotherapy-induced cognitive impairment (CICI). Mammary carcinoma was induced by subcutaneously inoculating 4T1 cells into the mammary fat pad of the animals. Intraperitoneal administration of Cyclophosphamide, Methotrexate, 5-Fluorouracil (CMF) regimen was carried out once a week for three weeks. Treatment of Mulmina began one week before chemotherapy and continued till the end of the chemotherapy cycle. After three cycles of chemotherapy, cognitive decline was assessed by Morris water maze task followed by assessment of locomotor activity by open-field test. Tumor progression was evaluated by measurement of tumor volume. Oxidative and neuroinflammatory markers were also evaluated from the isolated brain samples. CMF treatment resulted in a considerable reduction in tumour volume. We found chemotherapy negatively affected behavioral and biochemical parameters in animals and Mulmina treatment ameliorated these cognitive impairments by restoring antioxidant and maintaining cytokine levels. The combination of phytochemicals in Mulmina proved its possible ability to alleviate CICI without affecting chemotherapeutic efficiency and could pave the way for identifying treatment strategies to combat chemobrain.

The goal of this study was to provide an EEG profile of patients (150) with uncontrolled (U) seizures, in contrast with those (150) with controlled (C) attacks. In the U group 804 EEGs were done and in the C group 674 were performed, all with both waking and sleep recordings; the range of EEG records on a given patient was 2-23. The number of spikes and the amount of abnormal slowing was quantified in each record. Two different peaks of age were evident, appearing at 10-19 yrs and 40-49 yrs. The number of patients with a spike discharge on the first EEG was 64% in the C and 92% in the U group with an increasing incidence to 83% (C) and 100% (U) in later records. If spikes were absent in the first EEG in the C group, the majority showed only rare discharges later. The spike profile of the U patient initially was that 1/2 showed a typical number of spikes and nearly 1/2 many or very many spikes. Over time a decrease was seen in those with many-very many discharges, resulting in an increase with a typical number. Still later, a reversal occurred in the U patients with an increasing number with many or very many spikes. The slow wave profile of the U patient was that 2/3 showed some abnormal slow waves on the first record, increasing to 100% in later records. The increase was from delta, not theta activity. The spike profile of the C patient was that a typical number of spikes was seen at first in nearly 1/2, but only a small minority showed many-very many discharges. The slow wave profile for the C patient was that theta, not delta waves, increased in time. The (median) time between a unilateral spike discharge to a bilateral discharge was 4-5 yrs, and the U group much more often than the C group showed this change to bilateral spikes. The time between unilateral to bilateral slow waves varied between 4-9 yrs.

The management of breast cancer by chemotherapeutic agents has significantly increased the survival rates and, at the same time, raised concerns about the side effects caused by these agents on healthy tissues. Chemotherapy-induced cognitive impairment resulting from non-CNS malignancies like breast cancer has emerged as a significant challenge among cancer survivors due to its negative impact on the quality of day-to-day life activities. Using doxorubicin-based chemotherapy as a preclinical model for chemotherapy-induced cognitive impairment, we assessed the effect of quercetin on behavioral memory alterations in tumor-bearing female rats in vivo and changes in neurite length and apoptosis in PC12 cell lines in vitro. Quercetin is purported to have neuroprotective effects in different preclinical models of human neurological conditions because of its possible anti-inflammatory and antioxidant properties. Mammary carcinoma was induced by intraperitoneal administration of N-methyl-N-nitrosourea followed by doxorubicin administration once in 5 days (50 days). Pre-treatment with quercetin began 1 week before the chemotherapy and continued till the end of the chemotherapy cycle. Mechanistically, quercetin produced protection against doxorubicin-induced neurotoxicity by decreasing apoptosis and had a neurogenic effect evidenced by the prevention of toxicant-induced inhibition of neurite establishment. Quercetin reversed episodic and spatial memory deficits caused by doxorubicin treatment assessed by novel object recognition memory and Morris water maze, respectively. Taken together, our findings suggest that cytotoxic effects of doxorubicin may be a contributor to neurogenic impairment in tumor-bearing animals, leading to memory deficits. Therefore, quercetin could be a promising therapeutic strategy for doxorubicin-related cognitive impairment, thus imparting hope for improved quality of life among cancer survivors. Graphical Abstract

Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 with severe respiratory failure and organ damage that later appeared as a pandemic disease. Worldwide, people’s mental and physical health and socioeconomic have been affected. Currently, with no promising treatment for COVID-19, the existing anti-viral drugs and vaccines are the only hope to boost the host immune system to reduce morbidity and mortality rate. Unfortunately, several reports show that people who are partially or fully vaccinated are still susceptible to COVID-19 infection. Evidence suggests that COVID-19 immunopathology may include dysregulation of macrophages and monocytes, reduced type 1 interferons (IFN-1), and enhanced cytokine storm that results in hypersecretion of proinflammatory cytokines, capillary leak syndrome, intravascular coagulation, and acute respiratory distress syndrome (ARDS) ultimately leading to the worsening of patient’s condition and death in most cases. The recent use of cell-based therapies such as mesenchymal stem cells (MSCs) for critically ill COVID-19 patients has been authorized by the Food and Drug Administration (FDA) to alleviate cytokine release syndrome. It protects the alveolar epithelial cells by promoting immunomodulatory action and secreting therapeutic exosomes to improve lung function and attenuate respiratory failure. As a result, multiple clinical trials have been registered using MSCs that aim to use various cell sources, and dosages to promote safety and efficacy against COVID-19 infection. In this review, the possibility of using MSCs in COVID-19 treatment and its associated challenges in their use have been briefly discussed.

No abstract