More attention on glial cells to have better recovery after spinal cord injury

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury. © 2021 The Author

Scale-dependent non-Gaussianity and the CMB power asymmetry

We introduce an alternative parametrisation for the scale dependence of the non–linearity parameter fNL in quasi-local models of non–Gaussianity. Our parametrisation remains valid when fNL changes sign, unlike the commonly adopted power law ansatz fNL(k) ∝ knfNL. We motivate our alternative parametrisation by appealing to the self-interacting curvaton scenario, and as an application, we apply it to the CMB power asymmetry. Explaining the power asymmetry requires a strongly scale dependent non-Gaussianity. We show that regimes of model parameter space where fNL is strongly scale dependent are typically associated with a large gNL and quadrupolar power asymmetry, which can be ruled out by existing observational constraints

The hemispherical asymmetry from a scale-dependent inflationary bispectrum

If the primordial bispectrum is sufficiently large then the CMB hemispherical asymmetry may be explained by a large-scale mode of exceptional amplitude which perturbs the zeta two-point function. We extend previous calculations, which were restricted to one- or two-source scenarios, by providing a method to compute the response of the two-point function in any model yielding a 'local-like' bispectrum. In general, this shows that it is not the reduced bispectrum fNL which sources the amplitude and scale-dependence of the mode coupling but rather a combination of 'response functions'. We discuss why it is difficult to construct successful scenarios and enumerate the fine-tunings which seem to be required. Finally, we exhibit a concrete model which can be contrived to match the observational constraints and show that to a Planck-like experiment it would appear to have |fNL-local| ~ |fNL-equi| ~ |fNL-ortho| ~ 1. Therefore, contrary to previous analyses, we conclude that it is possible to generate the asymmetry while respecting observational constraints on the bispectrum and low-ell multipoles even without tuning our location on the long-wavelength mode

Squeezed tensor non-Gaussianity in non-attractor inflation

We investigate primordial tensor non-Gaussianity in single field inflation, during a phase of non-attractor evolution when the spectrum of primordial tensor modes can be enhanced to a level detectable at interferometer scales. Making use of a tensor duality we introduced in arXiv:1808.10475, we analytically compute the full bispectrum of primordial tensor fluctuations during the non-attractor era. During this epoch the shape of the tensor bispectrum is enhanced in the squeezed limit, its amplitude can be amplified with respect to slow-roll models, and tensor non-Gaussianity can exhibit a scale dependence distinctive of our set-up. We prove that our results do not depend on the frame used for the calculations. Squeezed tensor non-Gaussianity induces a characteristic quadrupolar anisotropy on the power spectrum of the stochastic background of primordial tensor perturbations. As a step to make contact with gravitational wave experiments, we discuss the response function of a ground based Michelson interferometer to a gravitational wave background with such a feature.Comment: 34 pages, 4 figure

Laterality and sex differences in the expression of brain-derived neurotrophic factor in developing rat hippocampus

Brain-derived neurotrophic factor (BDNF), as a member of neurotrophin family, plays an important role in neurogenesis, neuronal survival and synaptic plasticity. BDNF is strongly expressed in the hippocampus, where has been associated with memory consolidation, learning, and cognition. In this study, Real-time PCR, immunohistochemistry, and stereology were used to evaluate the gender differences and left-right asymmetries in the expression of BDNF in the developing rat hippocampus during the neurogenesis-active period, at postnatal days P0, P7 and P14. We found the lowest expression of BDNF in the right side and the highest in the left side hippocampi of both male and female neonates at P14 (P � 0.05 each). At the same time, there were significant differences in the hippocampal expression of BDNF between males and females (P � 0.05 each). No important differences in the number of BDNF expressing neurons in different subregions of right/left hippocampus were observed between male and female animals at P0 and P7 (P > 0.05). Furthermore, the highest numerical density of BDNF positive cells was detected in the both sides hippocampal CA1 in the male/female offspring at P7, and in the CA2, CA3 and dentate gyrus at P14 (P � 0.05 each). Based on these findings, it can be concluded that there are prominent sex and interhemispheric differences in the expression of BDNF in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development, structure, and function of the hippocampus. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

FNDC5 expression in Purkinje neurons of adult male rats with acute spinal cord injury following treatment with methylprednisolone

Spinal cord injury (SCI) is a serious and complex medical condition that can happen to anyone. At present, therapy mainly focuses on rehabilitation and pharmacological treatment, such as methylprednisolone (MP). Supra-spinal changes in certain structures, such as the cerebellum, that receive many afferents from the spinal cord might be one reason for unsuccessful therapeutic outcomes. Recently, the expression of FNDC5 was reported in cerebellar Purkinje cells as a possible neuroprotective agent. In the present study, we considered the expression of FNDC5 in Purkinje cells following SCI with and without MP administration in adult rats with SCI. Thirty-five adult male rats were used in this study. The animals were randomly allocated into five groups, including SCI, spinal cord injury with methylprednisolone treatment (SCI + MP), operation sham, control, and operation sham with MP. Induction of SCI was achieved by using special clips to compress the spinal cord at a determined level. After a certain interval time, the animals underwent study for FNDC5 expression, apoptosis by using immunohistochemistry, Western blotting, and TUNEL and Nissl staining. Our results showed a significant decrease in the number of Purkinje cells following SCI. Therapy with MP inhibits apoptosis in irFNDC5 Purkinje cells and restores them. Expression of FNDC5 significantly increased in SCI and decreased following MP therapy. We also showed other cerebellar cells with FNDC5 immunoreactivity in the two other cerebellar layers that were firstly reported. Since irisin is known as a plasma product of FNDC5, we think it might be a plasma marker following therapeutic efforts for SCI; however, it needs further research. In addition, it is possible that changes in FNDC5 expression in Purkinje cells might be related to neurogenesis in the cerebellum with unknown mechanisms. © 2018 Elsevier Lt

A survey on viewpoints of nursing and midwifery students and their clinical instructors at Faculty of Nursing and Midwifery of Shahid Sadoughi University of Medical Sciences towards clinical education during 2009-2011

Introduction: Clinical environments play a vital role in nursing and midwifery students' learning. The present study investigates the viewpoints of clinical instructors and nursing and midwifery students of Shahid Sadoughi University of Medical Sciences about clinical education status during 2009-2011. Methods: In this cross sectional research data were gathered using a researcher made questionnaire including five domains: educational plan, quality of clinical instructors function, role of clinical professionals in clinical education, educational facilities and space, clinical evaluation and professional satisfaction. The questionnaire was completed by clinical instructors and nursing and midwifery students. Convenient sampling was accomplished. Face validity, content validity and reliability of the questionnaire was assessed and confirmed by test – retest method. Results: Majority of clinical instructors, nursing and midwifery students reported day and evening work shifts more appropriate. Majority of clinical instructors reported the clinical education status pleasant, but 79.8% nursing students and 64.2% midwifery students reported it moderate. Comparing the mean of clinical education status from the viewpoints of clinical instructors didn't show a significant difference in the domain of "the role of the others impressive in clinical education", but there was a significant difference between the nursing and midwifery students in their view points about the domain. Conclusion: Clinical competency is an essential component in providing high quality nursing care, thus the educational planners should continue to evaluate the effectiveness of clinical education. Boosting the clinical learning environment domains such as “successful instructors”, “professional values”, “professional relationship with the members of caring team” and “conflict management” could make the clinical experience attractive and assure students’ satisfaction about their professional life

Maternal diabetes-induced alterations in the expression of brain-derived neurotrophic factor in the developing rat hippocampus

Maternal diabetes during pregnancy affects the development of hippocampus in the offspring. Brain-derived neurotrophic factor (BDNF) has received increasing attention for its role in regulating the survival and differentiation of neuronal cells in developing and adult brain. In the current study, we evaluated the effects of maternal diabetes and insulin treatment on expression and distribution pattern of BDNF in the hippocampus of neonatal rats at the first two postnatal weeks. We found no differences in hippocampal expression of BDNF between diabetics with normal control or insulin treated neonatal rats at postnatal day (P0) (P > 0.05 each). Nevertheless, there was a marked BDNF downregulation in both sides� hippocampi of male/female diabetic group in two-week-old offspring (P � 0.05 each). Furthermore, the numerical density of BDNF+ cells was significantly reduced in the right/left dentate gyrus (DG) of male and female newborns born to diabetic animals at all studied postnatal days (P � 0.05 each). In addition, a lower number of reactive cells have shown in the all hippocampal subareas in the diabetic pups at P14 (P � 0.05 each). Our results have demonstrated that the insulin-treatment improves some of the negative impacts of diabetes on the expression of hippocampal BDNF in the newborns. We conclude that diabetes in pregnancy bilaterally disrupts the expression of BDNF in the hippocampus of the both male and female newborns at early postnatal days. In addition, good glycemic control by insulin in the most cases is sufficient to prevent the alterations in expression of BDNF protein in developing hippocampus. © 2021 Elsevier B.V

miR-219 overexpressing oligodendrocyte progenitor cells for treating compression spinal cord injury

Oligodendrocyte progenitor cells (OPCs) transplantation has been considered a promising treatment for spinal cord injury, according to previous studies. Recent research shed light on the importance of microRNA 219 (miR-219) in oligodendrocyte development, so here miR-219-overexpressing OPCs (miR-219 OPCs) were transplanted in animal models of spinal cord injury to evaluate the impact of miR-219 on oligodendrocyte differentiation and functional recovery in vivo. Our findings demonstrate that transplanted cells were distributed in the tissue sections and contributed to reducing the size of cavity in the injury site. Interestingly, miR-219 promoted OPC differentiation into mature oligodendrocyte expressing MBP in vivo whereas in absence of miR-219, less number of cells differentiated into mature oligodendrocytes. An eight week evaluation using the Basso Beattie Bresnahan (BBB) locomotor test confirmed improvement in functional recovery of hind limbs. Overall, this study demonstrated that miR-219 promoted differentiation and maturation of OPCs after transplantation and can be used in cell therapy of spinal cord injury. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature

Targeting axonal degeneration and demyelination using combination administration of 17β-estradiol and Schwann cells in the rat model of spinal cord injury

Schwann cells (SCs) are known to be responsible for axonal ensheathing and myelination, and their transplantation is used commonly for treatment of spinal cord injury (SCI). 17β-estradiol (E2) has also reported for its protective roles in neurons in the transplanted SCs to the SCI model. In the current study, we evaluated the roles of E2 administration before SCs transplantation in targeting SCI-induced axonal degeneration and demyelination. E2 (25 µg/kg, IP) was administered to the male Wistar rats underwent contusive SCI at T10 segment. At 7 days after injury, 1 � 106 SCs were transplanted to the injury epicenter of the spinal cord. The groups were laminectomy, SCI, SCI+E2, and SCI+E2+SCs. Functional recovery was evaluated using the Basso-Bresnahan-Beattie locomotor test. Sections from spinal cord were also assessed for histoloical staining, including Luxol fast blue, Bielschowsky's silver and immunofluorescence evaluation of myelin basic protein (MBP). The SCI group showed impaired locomotion in the hind limb, increased number of cavities within spinal cord, low observable numbers of regenerating fibers, and a significant decrease in the rate of expression for MBP. These changes were counteracted in the treatment groups (P < 0.05 vs SCI) with no significant changes among them. From the results, it may be concluded that application of E2 and SCs could be effective when axons undergo demyelination and degenerative processes, and their combination could partly provide cumulative outcomes. © 2018 Wiley Periodicals, Inc