Neuroscience
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The benefits of Cochlear implant (CI) technology depend among other factors on the proximity of the electrode array to the spiral ganglion neurons. Laminin, a component of the extracellular matrix, regulates Schwann cell proliferation and survival as well as reorganization of actin fibers within their cytoskeleton, which is necessary for myelination of peripheral axons. In this study we explore the effectiveness of laminin-coated electrodes in promoting neuritic outgrowth from auditory neurons towards the electrode array and the ability to reduce acoustic and electric auditory brainstem response (i.e. aABR and eABR) thresholds. ⋯ In vivo: Animals implanted with laminin-coated electrodes experience significant decreases in eABR and aABR thresholds at selected frequencies compared to the results from the uncoated electrodes group. At 1 month post implantation there were a greater number of spiral ganglion neurons and neuritic processes projecting into the scala tympani of animals implanted with laminin-coated electrodes compared to animals with uncoated electrodes. These data suggest that Schwann cells are attracted towards laminin-coated electrodes and promote neuritic outgrowth/ guidance and promote the survival of spiral ganglion neurons following electrode insertion trauma.
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Temporal lobe epilepsy (TLE) is the commonest of adult epilepsies, often refractory to antiepileptic medications, whose prevention and treatment rely on understanding basic pathophysiological mechanisms in interlinked structures of the temporal lobe. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies have examined the role of the presubiculum (PrS) in mediating MEA pathophysiology but not the juxtaposed parasubiculum (Par). ⋯ These neurons experience significant reductions in synaptic inhibition and perish under chronic epileptic conditions. Connectivity between brain regions was deduced through changes in excitatory and inhibitory synaptic drive to neurons recorded in one region upon focal application of glutamate followed by NBQX to neurons in another using a microfluidic technique called CESOP and TLE-related circuit reorganization was assessed using data from normal and epileptic animals. The region-specific changes in Par and neighboring PrS and MEA together with their unexpected interactions are of significance in identifying ictogenic cells and circuits within the parahippocampal region and in unraveling pathophysiological mechanisms underlying TLE.
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Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. ⋯ DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA.
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In hypertensive retinopathy, the retinal damage due to high blood pressure is accompanied by increased expression of Glial Fibrillary Acidic Protein (GFAP), which indicates a role of neuroinflammatory processes in such a retinopathy. Proteins belonging to the Rho GTPase family, particularly Rac1, are involved in the activation of Müller glia and in the progression of photoreceptor degeneration, and may thus represent a novel candidate for therapeutic intervention following central nervous system inflammation. ⋯ Furthermore, such functional improvement is accompanied by a reduction of Rac1 activity and retinal GFAP expression. Our results suggest that Rac1 inhibition through CNF1 topical administration may represent a new strategy to target retinal gliosis.