Neuroscience
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Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. ⋯ The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery.
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The superior paraolivary nucleus (SPON) is a prominent structure in the mammalian auditory brainstem with a proposed role in encoding transient broadband sounds such as vocalized utterances. Currently, the source of excitatory pathways that project to the SPON and how these inputs contribute to SPON function are poorly understood. To shed light on the nature of these inputs, we measured evoked excitatory postsynaptic currents (EPSCs) in the SPON originating from the intermediate acoustic stria and compared them with the properties of EPSCs in the lateral superior olive (LSO) originating from the ventral acoustic stria during auditory development from postnatal day 5 to 22 in mice. ⋯ Evoked SPON excitation is comparatively weaker than evoked LSO excitation, likely due to a larger fraction of postsynaptic GluR2-containing Ca(2+)-impermeable AMPA receptors after hearing onset. Taken together, SPON excitation develops synaptic properties that are suited for transmitting single events with high temporal reliability and the strong, dynamic LSO excitation is compatible with high rate-level sensitivity. Thus, the excitatory input pathways to the SPON and LSO mature to support different decoding strategies of respective coarse temporal and sound intensity information at the brainstem level.
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The unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat is one of the most commonly used experimental models of Parkinson's disease (PD). Here we investigated whether magnetic resonance imaging (MRI) that is widely used in human PD research, has the potential to non-invasively detect macroscopic structural brain changes in the 6-OHDA rat in ways translatable to humans. ⋯ Unilateral nigrostriatal 6-OHDA lesioning leads to widespread GMV changes, which extend beyond the nigrostriatal system and resemble advanced Parkinsonism. This study highlights the potential of structural MRI, and VBM in particular, for the system-level phenotyping of rodent models of Parkinsonism and provides a methodological framework for future studies in novel rodent models as they become available to the research community.
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Recent discussions on the ethics in animal experimentation instigate the refinement of methods used in Behavioral Neuroscience, particularly regarding fear/anxiety paradigms. We propose the Light Switch-Off Test (LSOT), based on the innate motivation to cease an aversive stimulus (bright light), displayed naturally by rodents in their habitat. Forty-six male adult Wistar rats were allocated into independent groups: control, diazepam at 1 or 2mg/kg, and meta-Chlorophenylpiperazine (mCPP) at 0.5 or 1mg/kg. ⋯ Animals exposed solely to the box for the length of the test did not respond in a false positive way. Therefore, the SOR represents a good index to measure the innate rodent fear of bright-lighten areas, once they react quickly in order to turn off the stimulus. Among its many advantages, the LSOT is a simple, replicable, non-invasive and minimally stressful procedure, since it does not expose animals to excessively aversive stimulus.
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An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults. We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes. ⋯ Brief 4-6-Hz spike-wave discharges appeared de novo in the latent post-SE period and the acute administration of WIN55,212-2 also reduced the incidence of the epileptiform events. A single dose of WIN55,212-2 administered soon after SE improved survival of animals and reduced cell loss in the dentate hilus but did not prevent appearance of spontaneous recurrent seizures in the chronic period. Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.