Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia

Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Results: Intra�NRM injection of SNP (exogenous NO donor, 0.1� 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1� 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L�glutamate was reduced by prior intra NRM administration of NO synthase inhibitor NG�methyl�L�arginine or NG�nitro�L�arginine methyl ester (L�NAME, 0.1 μl, 100 nM). Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation. © 2015, Mashhad University of Medical Sciences. All rights reserved

VOCAL FOLD DYNAMICS DURING PHONATIONS

ABSTRACT During phonation, the vocal folds collision in the glottal closure is considered as a risk factor for pathology development. Based on the finite element model using the software ABAQUS TM , the impact stresses between the vocal folds are studied

PKC Mediates endogenous inhibition of myelin repair in the context of local demyelination induced in mice optic chiasm

Background: Axon regeneration in adult CNS is limited by the presence of inhibitory proteins associated with myelin. Although blocking PKC activity attenuates the ability of CNS myelin to inhibit neurite outgrowth, the role as well as mechanisms underlying the remyelination inhibition in CNS are still largely unknown. Considering the role of PKC in axonal regeneration and the vulnerability of optic chiasm in multiple sclerosis (MS), we assessed the effect of PKC inhibition on remyelination of lysolecithin induced demyelinated optic chiasm.Materials and Methods: Demyelination was induced by stereotaxic intra-chiasmatic injection of 1µl lysolecithin (1) in male mice. Intracerebroventricular daily injection of a PKC inhibitor (GO6976) was done for 14 days post-lesion. Demyelination and remyelination patterns in optic chiasm were confirmed through histological verification and electrophysiological study using Luxol fast blue staining and visual evoked potentials (VEP) recording, respectively.Results: In lysolecithin treated animals, demyelination was mostly marked at days 3 and 7 post-lesion and an incomplete remyelination occurred at day 14 post-lesion. VEP recording showed increased P-latency at the days 3 and 7 post-lesion while it partially decreased at day 14. Following the inhibition of PKC, while the extent of demyelination and P-latency slightly decreased at the days 3 and 7 post-lesion, it recovered at day 14. VEP recording data were confirmed by histological verification. Conclusion: Inhibition of PKC activity could represent a potential therapeutic approach for stimulating the remyelination process in the context of multiple sclerosis

PuraMatrix hydrogel enhances the expression of motor neuron progenitor marker and improves adhesion and proliferation of motor neuron-like cells

Objective(s): Cell therapy has provided clinical applications to the treatment of motor neuron diseases. The current obstacle in stem cell therapy is to direct differentiation of stem cells into neurons in the neurodegenerative disorders. Biomaterial scaffolds can improve cell differentiation and are widely used in translational medicine and tissue engineering. The aim of this study was to compare the efficiency of two-dimensional with a three-dimensional culture system in their ability to generate functional motor neuron-like cells from adipose-derived stem cells. Materials and Methods: We compared motor neuron-like cells derived from rat adipose tissue in differentiation, adhesion, proliferation, and functional properties on two-dimensional with three-dimensional culture systems. Neural differentiation was analyzed by immunocytochemistry for immature (Islet1) and mature (HB9, ChAT, and synaptophysin) motor neuron markers. Results: Our results indicated that the three-dimensional environment exhibited an increase in the number of Islet1. In contrast, two-dimensional culture system resulted in more homeobox gene (HB9), Choline Acetyltransferase (ChAT), and synaptophysin positive cells. The results of this investigation showed that proliferation and adhesion of motor neuron-like cells significantly increased in three-dimensional compared with two-dimensional environments. Conclusion: The findings of this study suggested that three-dimension may create a proliferative niche for motor neuron-like cells. Overall, this study strengthens the idea that three-dimensional culture may mimic neural stem cell environment for neural tissue regeneration

Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca2+ homeostasis. Changes in ADP-ribosyl cyclase (ADPRC), lysophosphatidic acid receptor 3 (LPAR3), calreticulin, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), synaptosomal nerve-associated protein 25 (SNAP 25) and transgelin 3 proteins were probed by Western blot analysis and validated using immunohistochemistry. Inhibition of calcium influx by 8-Bromo-cADP-Ribose (8-Br-cADPR) and 2-Aminoethyl diphenylborinate (2-APB) which act via the ADPRC and LPAR3, respectively, attenuated epileptic seizures. Considering a wide range of molecular events and effective role of calcium homeostasis in epilepsy, polypharmacy with multiple realistic targets should be further explored to reach the most effective treatments

Nogo Receptor Inhibition Enhances Functional Recovery following Lysolecithin-Induced Demyelination in Mouse Optic Chiasm

<div><p>Background</p><p>Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR) that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm.</p><p>Methodology/Principal Findings</p><p>A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down <i>NgR</i> levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs). Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+) migrated away from this area as a function of time.</p><p>Conclusions/Significance</p><p>Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.</p></div