Brain research
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Traumatic brain injury (TBI) is one of the largest health problems in the United States and affects both cognitive and motor function. Although weakness is common in TBI patients, few studies have demonstrated a reduction in strength in models of brain injury. ⋯ Following CCI, volitional forelimb strength is reduced by 36% and remains significantly reduced after 6 weeks of post-lesion training. We also show that CCI results in impairment of multiple additional measures of forelimb function for several weeks post-injury.
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The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. ⋯ CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug.
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Estrogen actions on neurons of the principal division of the bed nucleus of the stria terminalis (BNSTpr) are essential for the regulation of female sexual behavior. However, little is known about the effects of estradiol and progesterone (P) on estrogen receptor alpha (ERα) expression in this nucleus. To study this subject, we used stereological methods to estimate the total number of ERα-immunoreactive (ERα-ir) neurons in the BNSTpr of female rats at each stage of the estrous cycle and of ovariectomized rats after administration of estradiol benzoate (EB) and/or P. ⋯ PPT induced no changes in the number of ERα-ir neurons. Contrariwise, DPN induced a decrease in the total number of ERα-ir neurons to values similar to those of EB-treated rats. These results show that P has no effect in the modulation of ERα expression and demonstrate that estradiol regulation of ERα in BNSTpr neurons is mediated by activation of ERβ.
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Neurological complications contribute largely to the morbidity and mortality in patients with acute renal failure. In order to study pathophysiological complications of renal failure, a murine model of renal ischemia/reperfusion-induced acute kidney injury (AKI) was generated by 60min bilateral ischemia, and followed by 2h or 24h reperfusion (B-60'IRI). Compared to the sham-operated mice, B-60'IRI mice exhibited a significant inflammatory injury to remote brain. ⋯ The technology of cDNA microarray and quantitated RT-PCR are used to identify hippocampal genes whose expression is altered in response to AKI in B-60' IRI mice. The initiation of transcriptional abnormality was indicated by the finding that B-60' IRI mice exhibited upregulated mRNA levels of genes involved in inflammation, cell signaling, extracellular matrix and cell-cycle regulation and downregulated mRNA levels of genes involved in transporters, G protein-coupled receptor signaling, cell survival and chaperone. Our data suggest that renal IR contributes to a complicated hippocampal gene irregulation in inflammation and physiological homeostasis.
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Neuroinflammation with microglia activation (MA) constitutes a key tissue response in acute stroke. Until now, its course in the chronic stage is less well defined. Here, we investigated (i) neuroinflammation in the chronic stage of a rat model of embolic stroke (n=6), and (ii) whether this process can be visualized in vivo by multimodal imaging using Magnetic Resonance Imaging (MRI) and Positron-Emission-Tomography (PET). ⋯ Both, neuroinflammation and neurodegeneration were accessible to (immuno-) histochemical methods as well as to in vivo methods using [(11)C]PK11195-PET and T2(*)-weighted MRI. Although the functional roles of these dynamic processes remain to be elucidated, ongoing destruction of neuronal tissue is conceivable. Its inhibition using anti-inflammatory substances may be beneficial in chronic post-stroke conditions, while multimodal imaging can be used to evaluate putative therapeutic effects in vivo.