Brain research
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Endothelin B receptor agonist, IRL-1620, has been shown in previous studies, conducted in our lab, to provide significant neuroprotection at both 24h and 1 week following permanent cerebral ischemia. It is possible that IRL-1620 may be neuroprotective due to angiogenesis and neurogenesis. However, the effect of IRL-1620 on neurovascular remodeling following cerebral ischemia has not been established. ⋯ VEGF and NGF protein expression significantly increased at 1 week post MCAO in the infarcted hemisphere of IRL-1620 treated rats as compared to sham (P<0.01). Pretreatment with BQ788 blocked the effects of IRL-1620, thus confirming the role of ETB receptors in the neurovascular remodeling actions of IRL-1620. Results of the present study indicate that IRL-1620, administered on the day of infarct, is neuroprotective and enhances angiogenic and neurogenic remodeling following cerebral ischemia.
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Although protracted prefrontal gray matter development is associated with concomitant executive function (EF) development in adolescents, few studies have explored the relationship between white matter and EF. This study examined the relationship between white matter microstructure and two aspects of EF, inhibition and task-switching, in a sample of 84 adolescents using diffusion tensor imaging (DTI). Tract-Based Spatial Statistics (TBSS) were used to examine fractional anisotropy (FA) and mean diffusivity (MD). ⋯ There were no significant associations between MD and performance. Results suggest better inhibition and task-switching are associated with greater integrity of white matter microstructure in regions supporting cross-cortical and cortical-subcortical connections stemming from the prefrontal cortex. These findings are consistent with functional studies of cognitive control and models of EF that propose separate, yet related, latent factors.
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Stress predisposes the brain to various neuropathological disorders. Fibrates like gemfibrozil, commonly used for hyperlipidemia, have not yet been examined for their protective/deteriorative potential against restraint stress-induced disturbances. Pretreatment of rats with a range of gemfibrozil concentrations showed significant protection against stress consequences at 90 mg/kg of gemfibrozil, as it resulted in the highest level of antioxidant defense system potentiation among other doses. ⋯ Administration of gemfibrozil (90 mg/kg) before stress induction was able to significantly induce the protein levels of some protective factors including hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in the antioxidant nuclear factor erythroid-derived 2-like 2 (Nrf-2) pathway, as well as mitochondrial pro-survival proteins, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1). In parallel, the level of cleaved caspase-3 and apoptosis-inducing factor (AIF), two proteins involved in apoptotic cell death, and the number of damaged neurons detected in hematoxylin-eosin (H&E) stained hippocampus sections were suppressed in the presence of gemfibrozil. Herein, although gemfibrozil demonstrated protection against the restraint stress, considering its dose and context-dependent effects reported in the previous studies, as well as its common application in clinic, further investigations are essential to unravel its exact beneficial/deleterious effects in various neuronal contexts.
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The relationship between prenatal stress (PS) exposure and neurodevelopmental deficits remains inconclusive, especially when assessing the role of PS duration and timing and sex-dependent effects. This study explored a sex-specific association between the duration and timing of exposure and the outcomes of PS-induced neurotoxicity in hippocampal microstructure, synaptophysin expression, and neurobehavioral performance in rats. Pregnant rats were randomly assigned to control, PS-ML (exposed to prenatal restraint stress in the mid-to-late period of pregnancy), or PS-L (exposed in the late period of pregnancy) groups, and offspring in each group were divided into two subgroups by sex. ⋯ On postnatal day 22, hippocampal microstructure was examined by electron microscopy, and the expression of hippocampal synaptophysin was assessed by western blot. Abnormal ultrastructural appearance of hippocampal neurons and myelin sheaths, more degenerating neurons and higher G-ratios were found in young PS-ML and PS-L rats as well as reduced expression of hippocampal synaptophysin, although PS-ML pups were more greatly affected than PS-L, with males showing slightly greater impairments than females. These findings suggest that hippocampal hypo-myelination and decreased synaptophysin expression in neurodevelopment may be a duration and time-dependent effect of prenatal stress exposure, modified slightly by sex.
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This study addresses the spatial relation between local Na(+) and K(+) imbalances in the ischemic core in a rat model of focal ischemic stroke. Quantitative [Na(+)] and [K(+)] brain maps were obtained by (23)Na MRI and histochemical K(+) staining, respectively, and calibrated by emission flame photometry of the micropunch brain samples. Stroke location was verified by diffusion MRI, by changes in tissue surface reflectivity and by immunohistochemistry with microtubule-associated protein 2 antibody. ⋯ Some residual mismatch between the sites of maximum Na(+) and K(+) imbalances was attributed to the different channels and pathways involved in transport of the two ions. A linear regression of the [Na(+)]br vs. [K(+)]br in the samples of ischemic brain indicates that for each K(+) equivalent leaving ischemic tissue, 0.8±0.1 Eq, on average, of Na(+) enter the tissue. Better understanding of the mechanistic link between the Na(+) influx and K(+) egress would validate the (23)Na MRI slope as a candidate biomarker and a complementary tool for assessing ischemic damage and treatment planning.