Focal Injection of Ethidium Bromide as a Simple Model to Study Cognitive Deficit and Its Improvement

Introduction: Memory and cognitive impairments are some of devastating outcomes of Multiple Sclerosis (MS) plaques in hippocampus, the gray matter part of the brain. The present study aimed to evaluate the intrahippocampal injection of Ethidium Bromide (EB) as a simple and focal model to assess cognition and gray matter demyelination. Methods: Thirty Wistar rats were divided into three groups: control group, which received saline, as solvent of EB, into the hippocampus and two experimental groups, which received 3 &muL of EB into the hippocampus, and then, were evaluated 7 and 28 days after EB injection (n=10 in each group), using a 5-day protocol of Morris Water Maze (MWM) task as well as Transmission Electron Microscopy (TEM) assay. Results: Seven days after EB injection, the behavioral study revealed a significance increase in travelled distance for platform finding in the experimental group compared to the control group. In addition, the nucleus of oligodendrocyte showed the typical clumped chromatin, probably attributed to apoptosis, and the myelin sheaths of some axons were unwrapped and disintegrated. Twentyeight days after EB injection, the traveled distance and the time spent in target quadrant significantly decreased and increased, respectively in experimental groups compared to the control group. Also, TEM micrographs revealed a thin layer of remyelination around the axons in 28 days lesion group. Discussion: While intracerebral or intraventricular injection of EB is disseminated in different parts of the brain and can affect the other motor and sensory systems, this model is confined locally and facilitates behavioral study. Also, this project could show improvement of memory function subsequent to the physiological repair of the gray matter of the hippocampus

How does the impact of a community trial on cardio-metabolic risk factors differ in terms of gender and living area? Findings from the Isfahan healthy heart program

Objective: To assess the impact of gender and living area on cardiovascular risk factors in the context of a comprehensive lifestyle intervention program. Design: Data from independent sample surveys before (2000--2001) and after (2007) a community trial, entitled the Isfahan Healthy Heart Program (IHHP) were used to compare differences in the intervention area (IA) and reference area (RA) by gender and living area. Setting: The interventions targeted the population living in Isfahan and Najaf-Abad counties as IA and Arak as RA. Participants: Overall, 12 514 individuals who were more than 19 years of age were studied at baseline, and 9570 were studied in postintervention phase. Interventions: Multiple activities were conducted in connection with each of the four main strategies of healthy nutrition, increasing physical activity, tobacco control, and coping with stress. Main Outcomes: Comparing serum lipids levels, blood pressure, blood glucose and obesity indices changes between IA and RA based on sex and living areas during the study. Results: In IA, while the prevalence of hypertension declined in urban and rural females (P < 0.05). In IA, the prevalence of hypercholesterolemia and hypertriglyceridemia decreased in both females and males of urban and rural areas except for hypercholesterolemia in rural males (P < 0.01). In RA, the significant changes include both decrease in the hypercholesterolemia among rural males (P < 0.001) and hypertriglyceridemia in urban females (P < 0.01), while hypertriglyceridemia was significantly increased in rural females (P < 0.01). Conclusions: This comprehensive community trial was effective in controlling many risk factors in both sexes in urban and rural areas. These findings also reflect the transitional status of rural population in adopting urban lifestyle behaviors

How does the impact of a community trial on cardio-metabolic risk factors differ in terms of gender and living area? Findings from the Isfahan healthy heart program

Objective: To assess the impact of gender and living area on cardiovascular risk factors in the context of a comprehensive lifestyle intervention program. Design: Data from independent sample surveys before (2000--2001) and after (2007) a community trial, entitled the Isfahan Healthy Heart Program (IHHP) were used to compare differences in the intervention area (IA) and reference area (RA) by gender and living area. Setting: The interventions targeted the population living in Isfahan and Najaf-Abad counties as IA and Arak as RA. Participants: Overall, 12 514 individuals who were more than 19 years of age were studied at baseline, and 9570 were studied in postintervention phase. Interventions: Multiple activities were conducted in connection with each of the four main strategies of healthy nutrition, increasing physical activity, tobacco control, and coping with stress. Main Outcomes: Comparing serum lipids levels, blood pressure, blood glucose and obesity indices changes between IA and RA based on sex and living areas during the study. Results: In IA, while the prevalence of hypertension declined in urban and rural females (P < 0.05). In IA, the prevalence of hypercholesterolemia and hypertriglyceridemia decreased in both females and males of urban and rural areas except for hypercholesterolemia in rural males (P < 0.01). In RA, the significant changes include both decrease in the hypercholesterolemia among rural males (P < 0.001) and hypertriglyceridemia in urban females (P < 0.01), while hypertriglyceridemia was significantly increased in rural females (P < 0.01). Conclusions: This comprehensive community trial was effective in controlling many risk factors in both sexes in urban and rural areas. These findings also reflect the transitional status of rural population in adopting urban lifestyle behaviors

Mutant IDH1 and seizures in patients with glioma.

ObjectiveBecause the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons.MethodsThree WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5.ResultsPreoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1wt) patients and in 59%-74% of IDH1mut patients (p &lt; 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, p &lt; 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5.ConclusionsThe D2HG product of IDH1mut may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas

Mutant IDH1 and seizures in patients with glioma.

ObjectiveBecause the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons.MethodsThree WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5.ResultsPreoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1wt) patients and in 59%-74% of IDH1mut patients (p &lt; 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, p &lt; 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5.ConclusionsThe D2HG product of IDH1mut may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas