Neuroscience
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Regeneration in the adult mammalian spinal cord is limited due to intrinsic properties of mature neurons and a hostile environment, mainly provided by central nervous system myelin and reactive astrocytes. Recent results indicate that propriospinal connections are a promising target for intervention to improve functional recovery. To study this functional regeneration in vitro we developed a model consisting of two organotypic spinal cord slices placed adjacently on multi-electrode arrays. ⋯ This reduction was not accompanied by an inability for axons to cross the lesion site. We show that functional regeneration in these old cultures can be improved by increasing the intracellular cAMP level with Rolipram or by placing a young slice next to an old one directly after the lesion. We conclude that co-cultures of two spinal cord slices are an appropriate model to study functional regeneration of intraspinal connections.
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The aim of this study was to quantitatively assess the effects of short-term intermittent ethanol intoxication on cerebral metabolite changes among sham controls (CNTL), low-dose ethanol (LDE)-exposed, and high-dose ethanol (HDE)-exposed rats, which were determined with ex vivo high-resolution spectra. Eight-week-old male Wistar rats were divided into three groups. Twenty rats in the LDE (n=10) and the HDE (n=10) groups received ethanol doses of 1.5 and 2.5 g/kg, respectively, through oral gavage every 8h for 4days. ⋯ The six pairs of normalized metabolite levels were positively (+) or negatively (-) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and aspartate (Asp) (+), myo-Inositol (mIns) and Asp (-), mIns and alanine (+), mIns and taurine (+), and mIns and tNAA (-). Our results suggested that short-term intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo(1)H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of short-term intermittent ethanol intoxication in the frontal cortex.
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Guillain-Barré syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. ⋯ In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1β, interleukin-2, interleukin-6, inteleukin-12, interferon γ and tumor necrosis factor α, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.
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Hydrogen peroxide (H₂O₂) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H₂O₂ is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. ⋯ Hyperexcitability persisted with repeated H₂O₂ exposure. H₂O₂ effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H₂O₂ initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes.
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Developing new strategies to treat cerebral ischemic-reperfusion injury will require a better understanding of the mechanisms that underlie vascular permeability. In this study we examined the temporal expression of Src and angiogenic factors in rat brain after focal cerebral ischemia and reperfusion and analyzed the relationships among those factors. We also investigated the effect of Src inhibitor PP1 (4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) in ischemic reperfusion. ⋯ PP1 effectively decreased Src Y418 phosphorylation and the expression of VEGF and Ang-2 and increased the expression of Ang-1 and ZO-1. It also reduced cerebral infarct size and neurologic dysfunction. Therefore, Src may represent a new therapeutic target for reducing tissue damage caused by increased vascular permeability.