8-epi-prostaglandin-f2alpha and Cognition-Disorders

Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2α (8-iso-PGF2α), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso-PGF2α levels to predict POD and POCD in elderly patients undergoing hip fracture surgery.. Postoperative plasma 8-iso-PGF2α levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2α levels and the risk of POD and POCD using a multivariate analysis.. Plasma 8-iso-PGF2α levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso-PGF2α were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2α significantly enhanced the areas under curve of age for prediction of POD and POCD.. Postoperative plasma 8-iso-PGF2α levels may have the potential to predict POD and POCD in elder patients undergoing hip fracture surgery.

Topics: Aged; Cognition Disorders; Delirium; Dinoprost; Female; Hip Fractures; Humans; Male; Postoperative Period

Autism is a neurodevelopmental disorder that displays significant heterogeneity. Comparison of subgroups within autism, and analyses of selected biomarkers as measure of the variation of the severity of autistic features such as cognitive dysfunction, social interaction impairment, and sensory abnormalities might help in understanding the pathophysiology of autism.. In this study, two sets of biomarkers were selected. The first included 7, while the second included 6 biomarkers. For set 1, data were collected from 35 autistic and 38 healthy control participants, while for set 2, data were collected from 29 out of the same 35 autistic and 16 additional healthy subjects. These markers were subjected to a principal components analysis using either covariance or correlation matrices. Moreover, libraries composed of participants categorized into units were constructed. The biomarkers used include, PE (phosphatidyl ethanolamine), PS (phosphatidyl serine), PC (phosphatidyl choline), MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1), IL-10 (interleukin-10), IL-12, NFκB (nuclear factor-κappa B); PGE2 (prostaglandin E2), PGE2-EP2, mPGES-1 (microsomal prostaglandin synthase E-1), cPLA2 (cytosolic phospholipase A2), 8-isoprostane, and COX-2 (cyclo-oxygenase-2).. While none of the studied markers correlated with CARS and SRS as measure of cognitive and social impairments, six markers significantly correlated with sensory profiles of autistic patients. Multiple regression analysis identifies a combination of PGES, mPGES-1, and PE as best predictors of the degree of sensory profile impairment. Library identification resulted in 100% correct assignments of both autistic and control participants based on either set 1 or 2 biomarkers together with a satisfactory rate of assignments in case of sensory profile impairment using different sets of biomarkers.. The two selected sets of biomarkers were effective to separate autistic from healthy control subjects, demonstarting the possibility to accurately predict the severity of autism using the selected biomarkers. The effectiveness of the identified libraries lied in the fact that they were helpful in correctly assigning the study population as control or autistic patients and in classifying autistic patients with different degree of sensory profile impairment.

Topics: Adolescent; Autistic Disorder; Biomarkers; Child; Child, Preschool; Cognition Disorders; Cyclooxygenase 2; Dinoprost; Dinoprostone; Female; Humans; Interleukin-10; Interleukin-12; Male; MAP Kinase Kinase 1; NF-kappa B; Phosphatidylcholines; Phosphatidylserines; Phospholipases A2; Prostaglandin-E Synthases

To evaluate protective effects of inhaled hydrogen gas (H2) on cognitive function in a murine model of sepsis-associated encephalopathy (SAE).. A total of 84 male ICR mice, weighing 20-25 g, aged 6-8 weeks, were randomly divided into 4 groups of sham, sham+H2, sepsis and sepsis+H2. Sepsis was established by cecal ligation and puncture (CLP). Mice in sham+H2 and sepsis+H2 groups received 2% H2 inhalation for 1 h at 1 h and 6 h after sham operation or CLP operation respectively. The changes of neurological function and neuronal damage in hippocampal CA1 region were observed at 24 h post-operation. The activities of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in sera and hippocampus were detected at 24 h post-operation. The changes of cognitive function were observed by Y-maze test and fear conditional test at days 3 to 14 post-operation.. Compared with sham group, the neurological function significantly declined and neurons in hippocampal CA1 region were significantly damaged; the activities of SOD and CAT markedly decreased while the levels of MDA and 8-iso-PGF2α markedly increased in sera and hippocampus; the time in new zone and the percentage of freezing time dramatically decreased at days 3 to 14 post-operation in sepsis group (P < 0.05) . Compared with sepsis group, neurological function significantly improved and damaged neurons in hippocampal CA1 region significantly reduced; the activities of SOD and CAT markedly increased and the levels of MDA and 8-iso-PGF2α markedly decreased in sera and hippocampus; the time in new zone and the percentage of freezing time dramatically increased at days 3 to 14 post-operations in sepsis+H2 group (P < 0.05).. H2 inhalation can significantly alleviate neuronal damage and improve cognitive dysfunction in CLP-induced SAE mice. And it is probably associated with the increased activities of antioxidant enzymes and the reduced levels of oxidative products.

Topics: Animals; Cognition; Cognition Disorders; Dinoprost; Disease Models, Animal; Hippocampus; Hydrogen; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Neurons; Sepsis-Associated Encephalopathy; Superoxide Dismutase

Oxidative stress has been associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about oxidative stress in postoperative cognitive dysfunction (POCD) in aging. The aim of this study was to investigate urinary excretion rate of 8-isoprostane:creatinine (U8-isoPG:Cr) and malonaldehyde:creatinine (UMDA:Cr) to predict short-term POCD in elderly patients undergoing general and orthopedic surgery. 72 patients aged above 65 years were enrolled in this prospective observational study. Each patient underwent cognitive testing to determine POCD performed by an investigator before surgery and 1 week after surgery. Morning urine was collected at baseline, 1, 2, and 7 days postoperatively. U8-isoPG was performed using enzymelinked immunosorbent assay (ELISA), and UMDA levels were measured by chemiluminescence detection. Creatinine levels were also analyzed if differences in the oxidative biomarkers were observed in the urine creatinine concentration. (1). Of 72 patients who completed cognitive testing, postoperative cognitive dysfunction was detected in 29.2 % (n = 21) of patients in 7 days. (2) U8-isoPG:Cr levels in 7 days postoperatively were significantly higher in POCD patients compared with the non-POCD group (p = 0.01). When measuring change from baseline, U8-isoPG:Cr levels were higher than that of control groups (p = 0.01). (3) UMDA:Cr levels were significantly elevated in 1 and 2 days postoperatively in both groups (p < 0.05). U8-isoPG:Cr level seems to be a valuable marker to detect lipid peroxidation early in POCD patients. However, it will also be important to take into account or reduce potential confounders to improve the identification of changes in the status of oxidative stress as a marker for POCD.

Topics: Aged; Aging; Biomarkers; Cognition Disorders; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Luminescent Measurements; Male; Malondialdehyde; Neuropsychological Tests; Orthopedic Procedures; Oxidative Stress; Postoperative Complications; Postoperative Period

Early exposure to general anesthesia (GA) causes developmental neuroapoptosis in the mammalian brain and long-term cognitive impairment. Recent evidence suggests that GA also causes functional and morphological impairment of the immature neuronal mitochondria. Injured mitochondria could be a significant source of reactive oxygen species (ROS), which, if not scavenged in timely fashion, may cause excessive lipid peroxidation and damage of cellular membranes. We examined whether early exposure to GA results in ROS upregulation and whether mitochondrial protection and ROS scavenging prevent GA-induced pathomorphological and behavioral impairments. We exposed 7-day-old rats to GA with or without either EUK-134, a synthetic ROS scavenger, or R(+) pramipexole (PPX), a synthetic aminobenzothiazol derivative that restores mitochondrial integrity. We found that GA causes extensive ROS upregulation and lipid peroxidation, as well as mitochondrial injury and neuronal loss in the subiculum. As compared to rats given only GA, those also given PPX or EUK-134 had significantly downregulated lipid peroxidation, preserved mitochondrial integrity, and significantly less neuronal loss. The subiculum is highly intertwined with the hippocampal CA1 region, anterior thalamic nuclei, and both entorhinal and cingulate cortices; hence, it is important in cognitive development. We found that PPX or EUK-134 co-treatment completely prevented GA-induced cognitive impairment. Because mitochondria are vulnerable to GA-induced developmental neurotoxicity, they could be an important therapeutic target for adjuvant therapy aimed at improving the safety of commonly used GAs.

Topics: Age Factors; Analysis of Variance; Anesthesia, General; Animals; Animals, Newborn; Antioxidants; Benzothiazoles; Brain; Cognition Disorders; Dinoprost; Dose-Response Relationship, Drug; Drug Administration Schedule; Exploratory Behavior; Female; Lipid Peroxidation; Male; Maze Learning; Midazolam; Mitochondria; Organometallic Compounds; Oxygen; Pramipexole; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salicylates; Time Factors; Up-Regulation

It is widely accepted that oxidative stress is involved in the pathogenesis of Down syndrome, but the effectiveness of antioxidant treatment remains inconclusive. We tested whether chronic administration of α-tocopherol ameliorates the cognitive deficits exhibited by Ts65Dn mice, a mouse model of Down syndrome. α-Tocopherol was administered to pregnant Ts65Dn females, from the day of conception throughout the pregnancy, and to pups over their entire lifetime, from birth to the end of the behavioral testing period. Cognitive deficits were confirmed for Ts65Dn mice fed a control diet, revealing reduced anxiety or regardlessness in the elevated-plus maze task test and spatial learning deficits in the Morris water maze test. However, supplementation with α-tocopherol attenuated both cognitive impairments. In addition, we found that levels of 8-iso-prostaglandin F(2α) in brain tissue and hydroxyoctadecadienoic acid and 7-hydroxycholesterol in the plasma of Ts65Dn mice were higher than those of control mice. Supplementation with α-tocopherol decreased levels of lipid peroxidation products in Ts65Dn mice. Furthermore, we found out that α-tocopherol improved hypocellularity in the hippocampal dentate gyrus of Ts65Dn mice. These results imply that α-tocopherol supplementation from an early stage may be an effective treatment for the cognitive deficits associated with Down syndrome.

Topics: alpha-Tocopherol; Animals; Animals, Newborn; Brain; Cognition Disorders; Dinoprost; Disease Models, Animal; Down Syndrome; Fatty Acids, Unsaturated; Female; Free Radicals; Hippocampus; Hydroxycholesterols; Lipid Peroxidation; Maze Learning; Mice; Mice, Neurologic Mutants; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Space Perception