Gap between recognition and response to stroke scenarios among Saudi population: Cross-sectional survey study.

OBJECTIVES: Recognition of stroke symptoms and emergency medical services (EMS) calls have a significant impact on patient management and outcome after acute strokes. The objective of this study is to assess the presence of a gap in the Saudi population between the recognition of stroke symptoms and the appropriate response to call EMS. MATERIALS AND METHODS: This questionnaire-based, cross-sectional survey study was conducted among the Saudi population with 563 total participants. The data were collected using a self-administered, web-based questionnaire. It was distributed randomly via social media platforms and emails to the general population of Saudi Arabia (SA). A series of 12 vignettes of stroke scenarios and four non-stroke scenarios was adapted from validated instruments. RESULTS: Our study revealed that 8% (n = 533) of the responses were appropriately recognized and resulted in calls to EMS while 38% (n = 2,639) did not respond by calling EMS despite their correct recognition. However, 9% (n = 608) chose to call EMS regardless of their incorrect recognition of the stroke scenario, and the plurality, 45% (n = 3,096), did not recognize the stroke scenario or respond by calling EMS. Furthermore, we found a statistically significant association among appropriate response, recognition, and self-efficacy. CONCLUSIONS: A recognition-response gap has been found among the Saudi population. Future campaigns should focus on the identification of common stroke symptoms and reinforce the importance of calling the EMS to apply the knowledge appropriately. Consequently, such actions could decrease mortality and chronic disability among stroke patients.

Investigation of the optimal dose for experimental lipopolysaccharide-induced recognition memory impairment: behavioral and histological studies.

BACKGROUND: Lipopolysaccharide (LPS) administration is one of the most commonly used methods for inducing inflammation in animal models. Several animal studies have investigated the effects of acute and chronic peripheral administration of LPS on cognitive impairment. However, no previous study has compared the effects of different doses of chronically administered LPS on recognition memory performance. AIM: Here, we aimed to investigate the optimal dose of chronically administered LPS for the induction of recognition memory impairment in mice. MATERIALS AND METHODS: LPS at different doses (0.25, 0.50 and 0.75 mg/kg) was administered to SWR/J mice daily for 7 days. On day 9, the open field, novel object recognition and novel arm discrimination behavioral tests were performed. Additionally, prefrontal cortical histological examination was conducted. RESULTS: Compared with the control group, mice injected with 0.75 mg/kg LPS notably showed no object preference (familiar vs. novel), a reduction in the discrimination index, and spatial recognition impairment. Administration of the 0.25 and 0.50 mg/kg doses of LPS showed a preference for the novel object compared with the familiar object, had no significant impact on the discrimination index, and caused spatial recognition impairment. These behavioral results are in line with the histological examination of the prefrontal cortex, which revealed that the 0.75 mg/kg dose produced the most histological damage. CONCLUSIONS: Our findings suggest that for chronic peripheral administration of LPS, 0.75 mg/kg is the optimal dose for inducing neuroinflammation-associated recognition memory deficits.

Biochanin A Improves Memory Decline and Brain Pathology in Cuprizone-Induced Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural degeneration, and axonal loss. Cognitive impairment, including memory decline, is a significant feature in MS affecting up to 70% of patients. Thereby, it substantially impacts patients' quality of life. Biochanin A (BCA) is an o-methylated isoflavone with a wide variety of pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective activities. Thus, this study aimed to investigate the possible protective effects of BCA on memory decline in the cuprizone (CPZ) model of MS. Thirty Swiss albino male mice (SWR/J) were randomly divided into three groups (n = 10): control (normal chow + i.p. 1:9 mixture of DMSO and PBS), CPZ (0.2% w/w of CPZ mixed into chow + i.p. 1:9 mixture of DMSO and PBS), and CPZ + BCA (0.2% w/w of CPZ mixed into chow + i.p. 40 mg/kg of BCA). At the last week of the study (week 5), a series of behavioral tasks were performed. A grip strength test was performed to assess muscle weakness while Y-maze, novel object recognition task (NORT), and novel arm discrimination task (NADT) were performed to assess memory. Additionally, histological examination of the hippocampus and the prefrontal cortex (PFC) were conducted. BCA administration caused a significant increase in the grip strength compared with the CPZ group. Additionally, BCA significantly improved the mice's spatial memory in the Y-maze and recognition memory in the NORT and the NADT compared with the CPZ group. Moreover, BCA mitigated neuronal damage in the PFC and the hippocampus after five weeks of administration. In conclusion, our data demonstrates the possible protective effect of BCA against memory deterioration in mice fed with CPZ for five weeks.

Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach.

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

The Effect of Melatonin and Exercise on Social Isolation-Related Behavioral Changes in Aged Rats.

Social isolation (SI) is well established as an environmental factor that negatively influences different behavioral parameters, including cognitive function, anxiety, and social interaction, depending on the age of isolation. Aging is a physiological process that is associated with changes in cognitive function, locomotor activity, anxiety and emotional responses. Few studies have investigated the effect of SI in senescence, or possible interventions. In the current study, we investigated the possible complementary effects of melatonin (MLT) and exercise (Ex) in improving SI-related behavioral changes in aged rats. Forty aged Wistar rats (24 months old) were randomly divided into five groups (n = 8 per group): Control (group housing), SI (individual housing for 7 weeks), SI + MLT (SI rats treated with 0.4 mg MLT/ml in drinking water), SI + Ex (SI rats treated with 60 min of swimming), and SI + MLT + Ex (SI rats treated with both MLT and Ex). Different behavioral tasks were conducted in the following sequence: open field test, elevated plus maze test, sucrose preference test, Y maze test, and Morris water maze test. Locomotor activities measured by total distance moved and velocity revealed that SI + Ex (P = 0.0038; P = 0.0015) and SI + MLT + Ex (P = 0.0001; P = 0.0003) significantly improved the locomotor activity compared with SI rats but SI + MLT (P = 0.0599; P = 0.0627) rats showed no significant change. Anxiety index score was significantly improved in SI + MLT + Ex (P = 0.0256) compared with SI rats while SI + MLT (P > 0.9999) and SI + Ex (P = 0.2943) rats showed no significant change. Moreover, latency to reach the platform in Morris water maze was significantly reduced at day 5 in SI + MLT + Ex (P = 0.0457) compared with SI rats but no change was detected in SI + MLT (P = 0.7314) or SI + Ex (P = 0.1676) groups. In conclusion, this study supports the possible potential of MLT in combination with Ex in improving physical activity, anxiety, and cognitive functions in aging population.

BrainFD: Measuring the Intracranial Brain Volume With Fractal Dimension.

A few methods and tools are available for the quantitative measurement of the brain volume targeting mainly brain volume loss. However, several factors, such as the clinical conditions, the time of the day, the type of MRI machine, the brain volume artifacts, the pseudoatrophy, and the variations among the protocols, produce extreme variations leading to misdiagnosis of brain atrophy. While brain white matter loss is a characteristic lesion during neurodegeneration, the main objective of this study was to create a computational tool for high precision measuring structural brain changes using the fractal dimension (FD) definition. The validation of the BrainFD software is based on T1-weighted MRI images from the Open Access Series of Imaging Studies (OASIS)-3 brain database, where each participant has multiple MRI scan sessions. The software is based on the Python and JAVA programming languages with the main functionality of the FD calculation using the box-counting algorithm, for different subjects on the same brain regions, with high accuracy and resolution, offering the ability to compare brain data regions from different subjects and on multiple sessions, creating different imaging profiles based on the Clinical Dementia Rating (CDR) scores of the participants. Two experiments were executed. The first was a cross-sectional study where the data were separated into two CDR classes. In the second experiment, a model on multiple heterogeneous data was trained, and the FD calculation for each participant of the OASIS-3 database through multiple sessions was evaluated. The results suggest that the FD variation efficiently describes the structural complexity of the brain and the related cognitive decline. Additionally, the FD efficiently discriminates the two classes achieving 100% accuracy. It is shown that this classification outperforms the currently existing methods in terms of accuracy and the size of the dataset. Therefore, the FD calculation for identifying intracranial brain volume loss could be applied as a potential low-cost personalized imaging biomarker. Furthermore, the possibilities measuring different brain areas and subregions could give robust evidence of the slightest variations to imaging data obtained from repetitive measurements to Physicians and Radiologists.

The Effect of Short-Term Feeding of a High-Coconut Oil or High-Fat Diet on Neuroinflammation and the Performance of an Object-Place Task in Rats.

The consumption of high-fat and high-sugar diets, in the form of junk food, and binge eating are now common. Increasing evidence suggests that a high-fat diet (HFD) can induce neuroinflammation and alter behavior. I aimed to study the effects of diets of differing fat content on neuroinflammation and spatial memory using an object-place (OP) task. Thirty-two adult male rats were allocated to four groups and fed a regular diet (Regular diet), a control diet (Control diet), an HFD (60% of calories from lard), or a high-coconut oil diet (HCOD; 60% of calories from coconut oil) for 3 days. Their water intake, food consumption, body mass, and metabolic variables were measured. HFD-fed rats showed significantly poorer performance on the OP task, as assessed using the discrimination index (- 0.208 ± 0.094), than the Regular (0.462 ± 0.078; P < 0.0001) and Control (0.379 ± 0.081; P = 0.0003) groups. However, no significant difference was observed in spatial memory between the HCOD and Regular groups. The concentrations of neuroinflammatory markers (interleukin [IL]-1ß, IL-6, tumor necrosis factor α, and nuclear factor κB) were also measured in the hippocampus and prefrontal cortex. HFD-fed rats showed significantly higher levels of neuroinflammatory markers than the Regular and Control diet-fed groups. HCOD feeding did not induce neuroinflammation in the hippocampus and prefrontal cortex compared with the Regular and Control groups.

Melatonin improves memory defects in a mouse model of multiple sclerosis by up-regulating cAMP-response element-binding protein and synapse-associated proteins in the prefrontal cortex.

Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Melatonin can diffuse through the blood-brain barrier and has well-known antioxidant and anti-inflammatory properties with almost no side effects; it is, therefore, a promising neuroprotective supplement for many neurological diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, and fibromyalgia. However, only some researches have assessed the effect of melatonin on cognitive dysfunction in multiple sclerosis. Here, we evaluated the effects of melatonin supplementation on memory defects induced by cuprizone in a mouse model of multiple sclerosis. Cuprizone (400 mg/kg) and melatonin (80 mg/kg) were administered to SWR/J mice daily for 5 weeks. Open field, tail-flick, and novel object recognition behavioral tests were performed. Also, expression of cAMP-response element-binding protein, synaptophysin, and postsynaptic density protein 95 were measured in the prefrontal cortex. Melatonin significantly improved the memory defects induced by cuprizone toxicity by up-regulating cAMP-response element-binding protein and by increasing expression of the synapse-associated synaptophysin and postsynaptic density protein 95 genes in the prefrontal cortex. These results indicate that melatonin may provide protective effects against memory impairments associated with multiple sclerosis.

Neuroprotective Effects of Melatonin during Demyelination and Remyelination Stages in a Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive chronic inflammatory autoimmune disease of the myelin sheath, and melatonin is a powerful antioxidant and anti-inflammatory agent. The present study evaluated the protective effect of melatonin on demyelination and remyelination processes in male and female mice with experimental MS induced by cuprizone. This model of experimental MS in mice is widely used because cuprizone administration causes an artificial demyelination reaction through oligodendrocyte apoptosis, while its withdrawal leads to spontaneous remyelination. Male and female SWR/J mice (n = 78) were divided into three main groups (control, cuprizone, and cuprizone + melatonin), which were each further subdivided into males and females. Cuprizone was orally administered at a dose of 400 mg/kg/day by oral gavage for 5 weeks. In addition, melatonin was intraperitoneally administered for 9 weeks at a dose of 80 mg/kg/day. During the demyelination stage, melatonin exhibited a neuroprotective function in both male and female mice. This was evidenced by improved locomotor activity, increased antioxidant levels (catalase, superoxide dismutase, glutathione peroxidase, and glutathione), and reduced levels of malondialdehyde and inflammatory factors (interleukin-1 beta and tumor necrosis factor-alpha) in male and female mice. However, the effect of melatonin during the remyelination stage varied between sexes; male mice experienced protective effects following melatonin administration, whereas no effect was observed in female mice. These results suggest a complex interaction involving exogenous melatonin, remyelination, and endogenous female sex hormones.

Preferences of Academic Researches and Pattern of Utilization of Behavior Laboratory Science for Preclinical Researches - a Cross Sectional Study.

INTRODUCTION: Several studies confirmed the relation between mortality, behavioral and social factors and emphasized the importance of behavioral and social science to public health practice. AIM: This study aimed to determine the preferences of the researchers who utilize the behavioral sciences laboratory at the Preclinical Research Unit and define the patter of laboratory utilization in order to maximize the benefits gained from it. METHODS: This cross sectional study conducted at the KFMRC, KAU, Jeddah, Saudi Arabia in 2018 on the researchers who visited the behavior research laboratory between October 2018 and December 2018. A structured self-administered questionnaire was utilized to collect the demographic data and preferences of the participants and the pattern of utilization of the behavior science laboratory. The response rate was 100%. The Data were analyzed using the Statistical Package of Social Sciences (SPSS) version 21. RESULTS: About 47% of the participants were working at the faculty of medicine (FOM) and about 47% were assistant professor. About 53 had previously conducted researches in behaviors science field. The majority of the participants were interested in memory field (about 57%) followed by the social field (20%). The least attractive field were the nutritional and anxiety (1.4%). The percent of non-medical researchers who had no interest in co-ordination field was significantly higher (p=0.041) compared to the medical/paramedical specialists. CONCLUSION: This study shed the light on the relative reduced interest in behavior researches among the academic researchers. There is need for more orientation programs and campaigns to raise the awareness of the importance of behaviors researches laboratories and researches.

Possible prophylactic anti-excitotoxic and anti-oxidant effects of virgin coconut oil on aluminium chloride-induced Alzheimer's in rat models.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects an estimated 5.4 million people worldwide. However, there remains no curative treatment for the condition. Aß and hyperphosphorylated tau accumulation are the main hallmarks of the disease; they interfere with glutamate uptake and mediate glutamate excitotoxicity, oxidative stress, inflammation and neurodegeneration. As virgin coconut oil (VCO) is well-known as an antioxidant and anti-inflammatory natural compound, the purpose of the present study was to assess the possible prophylactic effect of VCO on aluminium chloride (AlCl3)- induced AD in rat. Alzheimer was induced by intraperitoneal injections of aluminium chloride (AlCl3) for 45 days (40 ml/kg per day), and our results showed that oral administration of VCO (5 ml per day for 30 days) prior to the administration of AlCl3 significantly reduced the glutamate level in both the hippocampus and prefrontal cortex compared to an VCO non-administrated AD group. Moreover, VCO significantly increased the glutathione (GSH) level in both the hippocampus and cortex and significantly decreased the malondialdehyde (MDA) level in only the cortex of the AlCl3-induced AD rat model compared to an AlCl3-induced AD rat model with no VCO. Our findings therefore show that VCO preserved the ultrastructural morphology of the hippocampus and cortex of the AlCl3-induced AD rat model, potentially providing protection against the neurodegeneration in AD of both cortical and hippocampal neurons. In conclusion, VCO has a potential prophylactic effect for memory enhancement, anti-excitotoxicity and antioxidants in AD model. AD is the leading cause of dementia worldwide, and it has no particular effective cure. The AD incidence rate increases with age and causes neurodegeneration and memory impairment. As virgin coconut oil (VCO) is well-known as an antioxidant and anti-inflammatory natural compound, this study focused on investigating the possible prophylactic effect of VCO on AD.