Table of Content

15 March 2017, Volume 12 Issue 3 Previous Issue    Next Issue

For Selected:

Download Citations EndNote Reference Manager ProCite BibTeX RefWorks

Toggle Thumbnails

Select

Correction: Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair Mikel Sánchez, Ane Garate, Diego Delgado, Sabino Padilla 2017, 12 (3):  338-338.  doi: 10.4103/1673-5374.202914 Abstract ( 124 )   PDF (171KB) ( 288 )   Save Related Articles | Metrics

Select

Neuroprotective mechanisms and translational potential of therapeutic hypothermia in the treatment of ischemic stroke Jin Hwan Lee, James Zhang, Shan Ping Yu 2017, 12 (3):  341-350.  doi: 10.4103/1673-5374.202915 Abstract ( 315 )   PDF (302KB) ( 693 )   Save Stroke is a leading cause of disability and death, yet effective treatments for acute stroke has been very limited. Thus far, tissue plasminogen activator has been the only FDA-approved drug for thrombolytic treatment of ischemic stroke patients, yet its application is only applicable to less than 4–5% of stroke patients due to the narrow therapeutic window (< 4.5 hours after the onset of stroke) and the high risk of hemorrhagic transformation. Emerging evidence from basic and clinical studies has shown that therapeutic hypothermia, also known as targeted temperature management, can be a promising therapy for patients with different types of stroke. Moreover, the success in animal models using pharmacologically induced hypothermia (PIH) has gained increasing momentum for clinical translation of hypothermic therapy. This review provides an updated overview of the mechanisms and protective effects of therapeutic hypothermia, as well as the recent development and findings behind PIH treatment. It is expected that a safe and effective hypothermic therapy has a high translational potential for clinical treatment of patients with stroke and other CNS injuries. Related Articles | Metrics

Select

Outdoor air pollution as a possible modifiable risk factor to reduce mortality in post-stroke population Anita Desikan 2017, 12 (3):  351-353.  doi: 10.4103/1673-5374.202917 Abstract ( 296 )   PDF (157KB) ( 392 )   Save Outdoor air pollution is a known risk factor for mortality and morbidity. The type of air pollutant most reliably associated with disease is particulate matter (PM), especially finer particulate matter that can reach deeper into the lungs like PM2.5 (particulate matter diameter < 2.5 μm). Some subpopulations may be particularly vulnerable to PM pollution. This review focuses on one subgroup, long-term stroke survivors, and the emerging evidence suggesting that survivors of a stroke may be at a higher risk from the deleterious effects of PM pollution. While the mechanisms for mortality are still under debate, long-term stroke survivors may be vulnerable to similar mechanisms that underlie the well-established association between PM pollution and cardiovascular disease. The fact that long-term stroke survivors of ischemic, but not hemorrhagic, strokes appear to be more vulnerable to the risk of death from higher PM pollution may also bolster the connection to ischemic heart disease. Survivors of an ischemic stroke may be more vulnerable to dying from higher concentrations of PM pollution than the general population. The clinical implications of this association suggest that reduced exposure to PM pollution may result in fewer deaths amongst stroke survivors. Related Articles | Metrics

Select

Novel insights into the role of NF-κB p50 in astrocytemediated fate specification of adult neural progenitor cells Valeria Bortolotto, Mariagrazia Grilli 2017, 12 (3):  354-357.  doi: 10.4103/1673-5374.202919 Abstract ( 313 )   PDF (371KB) ( 550 )   Save Within the CNS nuclear factor-kappa B (NF-κB) transcription factors are involved in a wide range of functions both in homeostasis and in pathology. Over the years, our and other groups produced a vast array of information on the complex involvement of NF-κB proteins in different aspects of postnatal neurogenesis. In particular, several extracellular signals and membrane receptors have been identified as being able to affect neural progenitor cells (NPC) and their progeny via NF-κB activation. A crucial role in the regulation of neuronal fate specification in adult hippocampal NPC is played by the NF-κB p50 subunit. NF-κB p50KO mice display a remarkable reduction in adult hippocampal neurogenesis which correlates with a selective defect in hippocampal-dependent short-term memory. Moreover absence of NF-κB p50 can profoundly affect the in vitro proneurogenic response of adult hippocampal NPC (ahNPC) to several endogenous signals and drugs. Herein we briefly review the current knowledge on the pivotal role of NF-κB p50 in the regulation of adult hippocampal neurogenesis. In addition we discuss more recent data that further extend the relevance of NF-κB p50 to novel astroglia-derived signals which can influence neuronal specification of ahNPC and to astrocyte-NPC cross-talk. Related Articles | Metrics

Select

Telomerase and mTOR in the brain: the mitochondria connection Satomi Miwa, Gabriele Saretzki 2017, 12 (3):  358-361.  doi: 10.4103/1673-5374.202922 Abstract ( 462 )   PDF (496KB) ( 563 )   Save Telomerase is an enzyme that maintains telomeres in dividing cells using a template on its inherent RNA component. Additionally, the protein part TERT (Telomerase Reverse Transcriptase) has various non-canonical functions. For example, it can localize to mitochondria under increased stress and protect cells in vitro from oxidative stress, DNA damage and apoptosis. Recently it has been demonstrated that TERT protein persists in adult neurons in the brain and data emerge suggesting that it might have a protective function in these post-mitotic cells as well. We have recently published that TERT protein accumulated in mitochondria from brain tissue of mice that have undergone short-term dietary restriction (DR) and rapamycin treatment. This localization correlated to lower levels of oxidative stress in these brain mitochondria. Since rapamycin treatment decreases mTOR signaling which is also thought to play an important role for the beneficial effects of DR, we conclude that the mTOR pathway might be involved in the TERT localization and its effects in brain mitochondria in vivo. These data are in line with previous findings from our group about increased mitochondrial localization of TERT in Alzheimer’s disease (AD) brains and a protective function of TERT protein in neurons in vitro against pathological tau. Related Articles | Metrics

Select

Tissue-type plasminogen activator is a homeostatic regulator of synaptic function in the central nervous system Valerie Jeanneret, Manuel Yepes 2017, 12 (3):  362-365.  doi: 10.4103/1673-5374.202924 Abstract ( 266 )   PDF (248KB) ( 345 )   Save Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons. Once in the synaptic cleft this tPA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles, and regulates the postsynaptic response to the presynaptic release of glutamate. Indeed, tPA has a bidirectional effect on the composition of the postsynaptic density (PSD) that does not require plasmin generation or the presynaptic release of glutamate, but varies according to the baseline level of neuronal activity. Hence, in inactive neurons tPA induces phosphorylation and accumulation in the PSD of the Ca2+/calmodulin-dependent protein kinase IIα (pCaMKIIα), followed by pCaMKIIα-induced phosphorylation and synaptic recruitment of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In contrast, in active neurons with increased levels of pCaMKIIα in the PSD tPA induces pCaMKIIα and pGluR1 dephosphorylation and their subsequent removal from the PSD. These effects require active synaptic N-methyl-D-aspartate (NMDA) receptors and cyclin-dependent kinase 5 (Cdk5)-induced phosphorylation of the protein phosphatase 1 (PP1) at T320. These data indicate that tPA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCaMKIIα /PP1 switch in the PSD. Related Articles | Metrics

Select

Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders Lir-Wan Fan, Yi Pang 2017, 12 (3):  366-371.  doi: 10.4103/1673-5374.202926 Abstract ( 263 )   PDF (219KB) ( 453 )   Save Embryonic neurogenesis is the process of generating neurons, the functional units of the brain. Because of its sensitivity to adverse intrauterine environment such as infection, dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders (ASD). Adult neurogenesis, although is restricted to a few neurogenic niches, plays pivotal roles in brain plasticity and repair. Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer’s disease. A hallmark feature of these brain disorders is neuroinflammation, which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment. In this review paper, we present evidence from both experimental and human studies to show a complex picture of relationship between these two events, and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders. Related Articles | Metrics

Select

Neuromelanin, one of the most overlooked molecules in modern medicine, is not a spectator Robert L. Haining, Cindy Achat-Mendes 2017, 12 (3):  372-375.  doi: 10.4103/1673-5374.202928 Abstract ( 590 )   PDF (337KB) ( 474 )   Save The loss of pigmented neurons from the human brain has long been the hallmark of Parkinson’s disease (PD). Neuromelanin (NM) in the pre-synaptic terminal of dopamine neurons is emerging as a primary player in the etiology of neurodegenerative disorders including PD. This mini-review discusses the interactions between neuromelanin and different molecules in the synaptic terminal and describes how these interactions might affect neurodegenerative disorders including PD. Neuromelanin can reversibly bind and interact with amine containing neurotoxins, e.g., MPTP, to augment their actions in the terminal, eventually leading to the instability and degeneration of melanin-containing neurons due to oxidative stress and mitochondrial dysfunction. In particular, neuromelanin appears to confer susceptibility to chemical toxicity by providing a large sink of iron-bound, heme-like structures in a pi-conjugated system, a system seemingly purposed to allow for stabilizing interactions including pi-stacking as well as ligand binding to iron. Given the progressive accumulation of NM with age corresponding with an apparent decrease in dopamine synthetic pathways, the immediate question of whether NM is also capable of binding dopamine, the primary functional monoamine utilized in this cell, should be raised. Despite the rather glaring implications of this finding, this idea appears not to have been adequately addressed. As such, we postulate on potential mechanisms by which dopamine might dissociate from neuromelanin and the implications of such a reversible relationship. Intriguingly, if neuromelanin is able to sequester and release dopamine in membrane bound vesicles, this intracellular pre-synaptic mechanism could be the basis for a form of chemical memory in dopamine neurons. Related Articles | Metrics

Select

Impacts of the retinal environment and photoreceptor type on functional regeneration Michèle G. DuVal, W. Ted Allison 2017, 12 (3):  376-379.  doi: 10.4103/1673-5374.202930 Abstract ( 272 )   PDF (497KB) ( 358 )   Save Retinal regeneration is a promising central nervous system (CNS) target amongst the various stem cell therapy pursuits, due to its accessibility for manipulation and its disposition towards longitudinal monitoring of treatment safety and efficacy. We offer our perspective on current hurdles towards functional regeneration of cone photoreceptors. Cones are key: For patients suffering vision loss, cone photoreceptors are a required cellular component to restoring daytime vision, colour vision, and high acuity vision. The challenges of regenerating cones contrast with logistic challenges of regenerating rod photoreceptors, which underlines the importance of evaluating context in degeneration and regeneration studies. Foundational research is required to delineate the factors required to generate a diversity of cones in the human macula, and to coax both remaining and newly regenerating cones to rewire towards restoring daytime colour vision. A complex interplay between cell-intrinsic factors and the retinal environment determine both the specification of cone fates and the synaptic plasticity enabling their functional integration. Recent revelations that cellular materials are transferred amongst photoreceptor progenitors further emphasize the critical role of neighbouring cells in directing stem cell fates. From our vantage point, translation of stem cell therapies to restore the cone-rich human macula must be borne upon foundational research in cone-rich retinas. Research frameworks centered on patient outcomes should prioritize animal models and functional outputs that enable and report functional restoration of cone-mediated vision. Related Articles | Metrics

Select

The emerging role of autophagic-lysosomal dysfunction in Gaucher disease and Parkinson’s disease Kerri J. Kinghorn, Amir M. Asghari, Jorge Iván Castillo-Quan 2017, 12 (3):  380-384.  doi: 10.4103/1673-5374.202934 Abstract ( 313 )   PDF (484KB) ( 321 )   Save Gaucher disease (GD), the commonest lysosomal storage disorder, results from the lack or functional deficiency of glucocerebrosidase (GCase) secondary to mutations in the GBA1 gene. There is an established association between GBA1 mutations and Parkinson’s disease (PD), and indeed GBA1 mutations are now considered to be the greatest genetic risk factor for PD. Impaired lysosomal-autophagic degradation of cellular proteins, including α-synuclein (α-syn), is implicated in the pathogenesis of PD, and there is increasing evidence for this also in GD and GBA1-PD. Indeed we have recently shown in a Drosophila model lacking neuronal GCase, that there are clear lysosomal-autophagic defects in association with synaptic loss and neurodegeneration. In addition, we demonstrated alterations in mechanistic target of rapamycin complex 1 (mTORC1) signaling and functional rescue of the lifespan, locomotor defects and hypersensitivity to oxidative stress on treatment of GCase-deficient flies with the mTOR inhibitor rapamycin. Moreover, a number of other recent studies have shown autophagy-lysosomal system (ALS) dysfunction, with specific defects in both chaperone-mediated autophagy (CMA), as well as macroautophagy, in GD and GBA1-PD model systems. Lastly we discuss the possible therapeutic benefits of inhibiting mTOR using drugs such as rapamycin to reverse the autophagy defects in GD and PD. Related Articles | Metrics

Select

The translational importance of establishing biomarkers of human spinal cord injury Sanam Salimi Elizei, Brian K. Kwon 2017, 12 (3):  385-388.  doi: 10.4103/1673-5374.202933 Abstract ( 199 )   PDF (182KB) ( 350 )   Save Our current dependence upon the clinical assessment of neurologic impairment renders many acute SCI patients ineligible for trials because they are not examinable. Furthermore, the difficulty in predicting neurologic recovery based on the early clinical assessment forces investigators to recruit large cohorts to have sufficient power. Biomarkers that objectively classify injury severity and better predict neurologic outcome would be valuable tools for translational research. As such, the objective of the present review was to describe some of the translational challenges in acute spinal cord injury research and examine the potential utility of neurochemical biomarkers found within cerebrospinal fluid and blood. We focus on published efforts to establish biological markers for accurately classifying injury severity and precisely predict neurological outcome. Related Articles | Metrics

Select

Neural grafting for Parkinson’s disease: challenges and prospects Thomas B. Stoker, Nicholas F. Blair, Roger A. Barker 2017, 12 (3):  389-392.  doi: 10.4103/1673-5374.202935 Abstract ( 187 )   PDF (193KB) ( 292 )   Save Parkinson’s disease (PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra. The motor disorder responds well to dopamine-replacement therapies, though these result in significant adverse effects due to non-physiological release of dopamine in the striatum, and off-target effects. Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine, in a physiological manner. Dopaminergic neurons for cell-based therapies can be obtained from several sources. Fetal ventral mesencephalon tissue contains dopaminergic neuron progenitors, and has been transplanted into the striatum of PD patients with good results in a number of cases. However, the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical setting. Induced pluripotent stem cells can be used to generate dopaminergic neurons for transplantation, providing a source of autologous tissue for grafting. This approach means that challenges associated with allografts, such as the potential for immune rejection, can be circumvented. However, the associated cost and difficulty in producing a standardized product from different cell lines means that, at present, this approach is not commercially viable as a cell-based therapy. Dopaminergic neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson’s disease, with trials due to commence in the next few years. Though there are ethical considerations to take into account when using embryonic tissue, the possibility of producing a standardized, optimized cell product means that this approach can be both effective, and commercially viable. Related Articles | Metrics

Select

The impact of vitamin D deficiency on neurogenesis in the adult brai Natalie J. Groves, Thomas H. J. Burne 2017, 12 (3):  393-394.  doi: 10.4103/1673-5374.202936 Abstract ( 453 )   PDF (141KB) ( 392 )   Save Related Articles | Metrics

Select

Regulation of neural stem/progenitor cell functions by P2X and P2Y receptors Peter Illes, Patrizia Rubini 2017, 12 (3):  395-396.  doi: 10.4103/1673-5374.202937 Abstract ( 353 )   PDF (150KB) ( 530 )   Save Related Articles | Metrics

Select

Small regulators making big impacts: regulation of neural stem cells by small non-coding RNAs Zhong Liu, Rui Zhao 2017, 12 (3):  397-398.  doi: 10.4103/1673-5374.202938 Abstract ( 199 )   PDF (230KB) ( 549 )   Save Related Articles | Metrics

Select

Targeting colony stimulating factor 1 receptor to prevent cognitive deficits induced by fractionated whole-brain irradiation Xi Feng, Susanna Rosi 2017, 12 (3):  399-400.  doi: 10.4103/1673-5374.202940 Abstract ( 285 )   PDF (142KB) ( 327 )   Save Related Articles | Metrics

Select

Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures Buqing Liang, Jason H. Huang 2017, 12 (3):  401-402.  doi: 10.4103/1673-5374.202939 Abstract ( 154 )   PDF (363KB) ( 318 )   Save Related Articles | Metrics

Select

Neurorestoration from medicinal plants: an opportunity to treat painful neuropathies Lorenzo Di Cesare Mannelli, Carla Ghelardini 2017, 12 (3):  403-404.  doi: 10.4103/1673-5374.202941 Abstract ( 315 )   PDF (312KB) ( 304 )   Save Related Articles | Metrics

Select

New approaches for prevention and treatment of Alzheimer’s disease: a fascinating challenge Luca Piemontese 2017, 12 (3):  405-406.  doi: 10.4103/1673-5374.202942 Abstract ( 188 )   PDF (134KB) ( 348 )   Save Related Articles | Metrics

Select

Amyotrophic lateral sclerosis disease modifying therapeutics: a cell biological perspective Bor Luen Tang 2017, 12 (3):  407-408.  doi: 10.4103/1673-5374.202943 Abstract ( 271 )   PDF (146KB) ( 320 )   Save Related Articles | Metrics

Select

Electroacupuncture reduces apoptotic index and inhibits p38 mitogen-activated protein kinase signaling pathway in the hippocampus of rats with cerebral ischemia/reperfusion injury Xiao Lan, Xin Zhang, Guo-ping Zhou, Chun-xiao Wu, Chun Li, Xiu-hong Xu 2017, 12 (3):  409-416.  doi: 10.4103/1673-5374.202944 Abstract ( 296 )   PDF (1171KB) ( 412 )   Save Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury. To further identify the involved mechanisms, we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa’s method. At 30 minutes before model establishment, p38 MAPK blocker SB20358 was injected into the left lateral ventricles. At 1.5 hours after model establishment, electroacupuncture was administered at acupoints of Chize (LU5), Hegu (LI4), Zusanli (ST36), and Sanyinjiao (SP6) for 20 minutes in the affected side. Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores, but no significant differences were determined among different interventional groups. Hematoxylin-eosin staining also showed reduced brain tissue injuries. Compared with the SB20358 group, the cells were regularly arranged, the structures were complete, and the number of viable neurons was higher in the SB20358 + electroacupuncture group. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assay showed a decreased apoptotic index in each group, with a significant decrease in the SB20358 + electroacupuncture group. Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group. There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group. These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway. A time period of 3 days could promote the repair of ischemic cerebral nerves. Related Articles | Metrics

Select

Neuroprotective effects of autophagy inhibition on hippocampal glutamate receptor subunits after hypoxiaischemia-induced brain damage in newborn rats Li-xiao Xu, Xiao-juan Tang, Yuan-yuan Yang, Mei Li, Mei-fang Jin, Po Miao, Xin Ding, Ying Wang, Yan-hong Li, Bin Sun, Xing Feng 2017, 12 (3):  417-424.  doi: 10.4103/1673-5374.202945 Abstract ( 240 )   PDF (2466KB) ( 463 )   Save Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage (HIBD). However, its regulatory role in HIBD remains unclear and was thus examined here using a rat model. To induce HIBD, the left common carotid artery was ligated in neonatal rats, and the rats were subjected to hypoxia for 2 hours. Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine (10 mM in 10 μL) or the autophagy stimulator rapamycin (1 g/kg) 1 hour before artery ligation. Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR1, but by reduced expression of GluR2. Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury, whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury. Additionally, 3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of GluR1 and downregulation of GluR2 in the hippocampus. By contrast, rapamycin further elevated hippocampal GluR1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD. Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats, at least in part, through normalizing GluR1 and GluR2 expression. Related Articles | Metrics

Select

Fermented Chinese formula Shuan-Tong-Ling attenuates ischemic stroke by inhibiting inflammation and apoptosis Zhi-gang Mei, Ling-jing Tan, Jin-feng Wang, Xiao-li Li, Wei-feng Huang, Hua-jun Zhou 2017, 12 (3):  425-432.  doi: 10.4103/1673-5374.202946 Abstract ( 335 )   PDF (892KB) ( 500 )   Save The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae (Gegen), salvia miltiorrhiza (Danshen), radix curcuma (Jianghuang), hawthorn (Shanzha), salvia chinensis (Shijianchuan), sinapis alba (Baijiezi), astragalus (Huangqi), panax japonicas (Zhujieshen), atractylodes macrocephala koidz (Baizhu), radix paeoniae alba (Baishao), bupleurum (Chaihu), chrysanthemum (Juhua), rhizoma cyperi (Xiangfu) and gastrodin (Tianma), whose aqueous extract was fermented with lactobacillus, bacillus aceticus and saccharomycetes. Shuan-Tong-Ling is a formula used to treat brain diseases including ischemic stroke, migraine, and vascular dementia. Shuan-Tong-Ling attenuated H2O2-induced oxidative stress in rat microvascular endothelial cells. However, the potential mechanism involved in these effects is poorly understood. Rats were intragastrically treated with 5.7 or 17.2 mL/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced. The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores. Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side. In addition, Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax. Injection of 5 mg/kg silent information regulator 1 (SIRT1) inhibitor EX527 into the subarachnoid space once every 2 days, four times, reversed the above changes. These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway. Related Articles | Metrics

Select

Neural stem cells over-expressing brain-derived neurotrophic factor promote neuronal survival and cytoskeletal protein expression in traumatic brain injury sites Tao Chen, Yan Yu, Liu-jiu Tang, Li Kong, Cheng-hong Zhang, Hai-ying Chu, Liang-wei Yin, Hai-ying Ma 2017, 12 (3):  433-439.  doi: 10.4103/1673-5374.202947 Abstract ( 405 )   PDF (1076KB) ( 477 )   Save Cytoskeletal proteins are involved in neuronal survival. Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury. However, the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear. To examine this, we established a rat model of traumatic brain injury by controlled cortical impact. At 72 hours after injury, 2 × 107 cells/mL neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells (3 mL) were injected into the injured cortex. At 1–3 weeks after transplantation, expression of neurofilament 200, microtubule-associated protein 2, actin, calmodulin, and beta-catenin were remarkably increased in the injury sites. These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival, growth, and differentiation in the injury sites. The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway. Related Articles | Metrics

Select

Stress injuries and autophagy in mouse hippocampus after chronic cold exposure Ting-ting Qu, Jie-xin Deng,Rui-ling Li, Zhan-jun Cui, Xiao-qing Wang, Lai Wang, Jin-bo Deng 2017, 12 (3):  440-446.  doi: 10.4103/1673-5374.202932 Abstract ( 437 )   PDF (1891KB) ( 502 )   Save Cold exposure is an external stress factor that causes skin frostbite as well as a variety of diseases. Estrogen might participate in neuroprotection after cold exposure, but its precise mechanism remains unclear. In this study, mice were exposed to 10°C for 7 days and 0–4°C for 30 days to induce a model of chronic cold exposure. Results showed that oxidative stress-related c-fos and cyclooxygenase 2 expressions, MAP1LC3-labeled autophagic cells, Iba1-labeled activated microglia, and interleukin-1β-positive pyramidal cells were increased in the hippocampal CA1 area. Chronic cold exposure markedly elevated the levels of estrogen in the blood and the estrogen receptor, G protein-coupled receptor 30. These results indicate that neuroimmunoreactivity is involved in chronic cold exposure-induced pathological alterations, including oxidative stress, neuronal autophagy, and neuroimmunoreactivity. Moreover, estrogen exerts a neuroprotective effect on cold exposure. Related Articles | Metrics

Select

Modulation of neuronal dynamic range using two different adaptation mechanism Lei Wang, Ye Wang, Wen-long Fu, Li-hong Cao 2017, 12 (3):  447-451.  doi: 10.4103/1673-5374.202931 Abstract ( 201 )   PDF (1046KB) ( 529 )   Save The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents) in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered) adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range. Related Articles | Metrics

Select

Guinea pigs as an animal model for sciatic nerve injury Malik Abu Rafee, Amarpal, Prakash Kinjavdekar, Hari Prasad Aithal, Sajad Ahmad Wani, Irfan Ahmad Bhat 2017, 12 (3):  452-457.  doi: 10.4103/1673-5374.202929 Abstract ( 284 )   PDF (1047KB) ( 615 )   Save The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1) gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2) gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters. Related Articles | Metrics

Select

Combination therapy using evening primrose oil and electrical stimulation to improve nerve function following a crush injury of sciatic nerve in male rats Omid Badri, Parviz Shahabi, Jalal Abdolalizadeh, Mohammad Reza Alipour, Hadi Veladi, Mehdi Farhoudi, Mohsen Sharif Zak 2017, 12 (3):  458-463.  doi: 10.4103/1673-5374.202927 Abstract ( 317 )   PDF (1335KB) ( 732 )   Save Peripheral nerve injuries with a poor prognosis are common. Evening primrose oil (EPO) has beneficial biological effects and immunomodulatory properties. Since electrical activity plays a major role in neural regeneration, the present study investigated the effects of electrical stimulation (ES), combined with evening primrose oil (EPO), on sciatic nerve function after a crush injury in rats. In anesthetized rats, the sciatic nerve was crushed using small haemostatic forceps followed by ES and/or EPO treatment for 4 weeks. Functional recovery of the sciatic nerve was assessed using the sciatic functional index. Histopathological changes of gastrocnemius muscle atrophy were investigated by light microscopy. Electrophysiological changes were assessed by the nerve conduction velocity of sciatic nerves. Immunohistochemistry was used to determine the remyelination of the sciatic nerve following the interventions. EPO + ES, EPO, and ES obviously improved sciatic nerve function assessed by the sciatic functional index and nerve conduction velocity of the sciatic nerve at 28 days after operation. Expression of the peripheral nerve remyelination marker, protein zero (P0), was increased in the treatment groups at 28 days after operation. Muscle atrophy severity was decreased significantly while the nerve conduction velocity was increased significantly in rats with sciatic nerve injury in the injury + EPO + ES group than in the EPO or ES group. Totally speaking, the combined use of EPO and ES may produce an improving effect on the function of sciatic nerves injured by a crush. The increased expression of P0 may have contributed to improving the functional effects of combination therapy with EPO and ES as well as the electrophysiological and histopathological features of the injured peripheral nerve. Related Articles | Metrics

Select

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats Chao Deng, Ya-juan Gu, Hong Zhang1, Jun Zhang 2017, 12 (3):  464-469.  doi: 10.4103/1673-5374.202925 Abstract ( 310 )   PDF (827KB) ( 376 )   Save Estrogen affects the generation and transmission of neuropathic pain, but the specific regulatory mechanism is still unclear. Activation of the N-methyl-D-aspartate acid receptor 1 (NMDAR1) plays an important role in the production and maintenance of hyperalgesia and allodynia. The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain. A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats. These rats were then subcutaneously injected with 17β-estradiol, the NMDAR1 antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP-5), or both once daily for 15 days. Compared with injured drug naïve rats, rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency, indicating increased sensitivity to mechanical and thermal pain. Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity (as assessed by immunohistochemistry) and protein (as determined by western blot assay) in spinal dorsal root ganglia. This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5, whereas AP-5 alone did not affect NMDAR1 expression. These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve, and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia. Related Articles | Metrics

Select

The mechanism of Naringin-enhanced remyelination after spinal cord injury Wei Rong, Yong-wei Pan, Xu Cai, Fei Song, Zhe Zhao, Song-hua Xiao, Cheng Zhang 2017, 12 (3):  470-477.  doi: 10.4103/1673-5374.202923 Abstract ( 301 )   PDF (1480KB) ( 465 )   Save Our previous study revealed that intragastric administration of naringin improved remyelination in rats with spinal cord injury and promoted the recovery of neurological function of the injured spinal cord. This study sought to reveal the mechanisms by which naringin improves oligodendrocyte precursor cell differentiation and maturation, and promotes remyelination. Spinal cord injury was induced in rats by the weight-drop method. Naringin was intragastrically administered daily (20, 40 mg/kg) for 4 weeks after spinal cord injury induction. Behavioral assessment, histopathological staining, immunofluorescence spectroscopy, ultrastructural analysis and biochemical assays were employed. Naringin treatment remarkably mitigated demyelination in the white matter, increased the quality of myelinated nerve fibers and myelin sheath thickness, promoted oligodendrocyte precursor cell differentiation by upregulating the expression of NKx2.2 and 2′3′-cyclic nucleotide 3′-phosphodiesterase, and inhibited β-catenin expression and glycogen synthase kinase-3β (GSK-3β) phosphorylation. These findings indicate that naringin treatment regulates oligodendrocyte precursor cell differentiation and promotes remyelination after spinal cord injury through the β-catenin/GSK-3β signaling pathway. Related Articles | Metrics

Select

Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injur Wei Zhao, Yong Chai, Yun Hou, Da-wei Wang, Jian-qiang Xing, Cheng Yang, Qing-min Fang 2017, 12 (3):  478-485.  doi: 10.4103/1673-5374.202921 Abstract ( 361 )   PDF (1921KB) ( 419 )   Save Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury. A rat model of spinal cord injury was established via dorsal complete transection at the T10 vertebra. The rats received an intraperitoneal injection of epothilone B (0.75 mg/kg) at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group. Neuron-glial antigen 2, platelet-derived growth factor receptor β, and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group, but β-tubulin protein expression was greater. Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment. The Basso, Beattie, and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group. The results of this study demonstrated that epothilone B reduced the number of pericytes, inhibited extracellular matrix formation, and suppressed scar formation after spinal cord injury. Related Articles | Metrics

Select

Anatomical distributional defects in mutant genes associated with dominant intermediate Charcot-Marie-Tooth disease type C in an adenovirus-mediated mouse model SeoJin Lee, Sandesh Panthi, Hyun Woo Jo, Jaeyoung Cho, Min-Sik Kim, Na Young Jeong, In Ok Song, Junyang Jung, Youngbuhm Huh 2017, 12 (3):  486-492.  doi: 10.4103/1673-5374.202920 Abstract ( 306 )   PDF (1193KB) ( 359 )   Save Dominant intermediate Charcot-Marie-Tooth disease type C (DI-CMTC) is a dominantly inherited neuropathy that has been classified primarily based on motor conduction velocity tests but is now known to involve axonal and demyelination features. DI-CMTC is linked to tyrosyl-tRNA synthetase (YARS)-associated neuropathies, which are caused by E196K and G41R missense mutations and a single de novo deletion (153-156delVKQV). It is well-established that these YARS mutations induce neuronal dysfunction, morphological symptoms involving axonal degeneration, and impaired motor performance. The present study is the first to describe a novel mouse model of YARS-mutation-induced neuropathy involving a neuron-specific promoter with a deleted mitochondrial targeting sequence that inhibits the expression of YARS protein in the mitochondria. An adenovirus vector system and in vivo techniques were utilized to express YARS fusion proteins with a Flag-tag in the spinal cord, peripheral axons, and dorsal root ganglia. Following transfection of YARS-expressing viruses, the distributions of wild-type (WT) YARS and E196K mutant proteins were compared in all expressed regions; G41R was not expressed. The proportion of Flag/green fluorescent protein (GFP) double-positive signaling in the E196K mutant-type mice did not significantly differ from that of WT mice in dorsal root ganglion neurons. All adenovirus genes, and even the empty vector without the YARS gene, exhibited GFP-positive signaling in the ventral horn of the spinal cord because GFP in an adenovirus vector is driven by a cytomegalovirus promoter. The present study demonstrated that anatomical differences in tissue can lead to dissimilar expressions of YARS genes. Thus, use of this novel animal model will provide data regarding distributional defects between mutant and WT genes in neurons, the DI-CMTC phenotype, and potential treatment approaches for this disease. Related Articles | Metrics

Select

Transplantation of autologous peripheral blood mononuclear cells in the subarachnoid space for amyotrophic lateral sclerosis: a safety analysis of 14 patient Xiao-yan Li, Zhan-hua Liang, Chao Han, Wen-juan Wei, Chun-li Song, Li-na Zhou, Yang Liu, Ying Li, Xiao-fei Ji, Jing Liu 2017, 12 (3):  493-498.  doi: 10.4103/1673-5374.202918 Abstract ( 194 )   PDF (632KB) ( 313 )   Save There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis. The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials. After stem cell mobilization and collection, autologous peripheral blood mononuclear cells (1 × 109) were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients. The primary outcome measure was incidence of adverse events. Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation, Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale 1 week preoperatively and 1, 2, 4 and 12 weeks postoperatively. There was no immediate or delayed transplant-related cytotoxicity. The number of leukocytes, serum alanine aminotransferase and creatinine levels, and body temperature were within the normal ranges. Radiographic evaluation showed no serious transplant-related adverse events. Muscle strength grade, results of Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale were not significantly different before and after treatment. These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe, but its therapeutic effect is not remarkable. Thus, a large-sample investigation is needed to assess its efficacy further. Related Articles | Metrics

Select

Anesthetic considerations for patients with acute cervical spinal cord injury Fang-ping Bao, Hong-gang Zhang, Sheng-mei Zhu 2017, 12 (3):  499-504.  doi: 10.4103/1673-5374.202916 Abstract ( 189 )   PDF (244KB) ( 315 )   Save Anesthesiologists work to prevent or minimize secondary injury of the nervous system and improve the outcome of medical procedures. To this end, anesthesiologists must have a thorough understanding of pathophysiology and optimize their skills and equipment to make an anesthesia plan. Anesthesiologists should conduct careful physical examinations of patients and consider neuroprotection at preoperative interviews, consider cervical spinal cord movement and compression during airway management, and suggest awake fiberoptic bronchoscope intubation for stable patients and direct laryngoscopy with manual in-line immobilization in emergency situations. During induction, anesthesiologists should avoid hypotension and depolarizing muscle relaxants. Mean artery pressure should be maintained within 85–90 mmHg (1 mmHg = 0.133 kPa; vasoactive drug selection and fluid management). Normal arterial carbon dioxide pressure and normal blood glucose levels should be maintained. Intraoperative neurophysiological monitoring is a useful option. Anesthesiologists should be attentive to postoperative respiratory insufficiency (carefully considering postoperative extubation), thrombus, and infection. In conclusion, anesthesiologists should carefully plan the treatment of patients with acute cervical spinal cord injuries to protect the nervous system and improve patient outcome. Related Articles | Metrics