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15 July 2018, Volume 13 Issue 7 Previous Issue    Next Issue

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The impact of hypoxic-ischemic brain injury on stem cell mobilization, migration, adhesion, and proliferation Stephanie M. Parry, Eric S. Peeples 2018, 13 (7):  1125-1135.  doi: 10.4103/1673-5374.235012 Abstract ( 142 )   PDF (554KB) ( 322 )   Save Neonatal hypoxic-ischemic encephalopathy continues to be a significant cause of death or neurodevelopmental delays despite standard use of therapeutic hypothermia. The use of stem cell transplantation has recently emerged as a promising supplemental therapy to further improve the outcomes of infants with hypoxic-ischemic encephalopathy. After the injury, the brain releases several chemical mediators, many of which communicate directly with stem cells to encourage mobilization, migration, cell adhesion and differentiation. This manuscript reviews the biomarkers that are released from the injured brain and their interactions with stem cells, providing insight regarding how their upregulation could improve stem cell therapy by maximizing cell delivery to the injured tissue. Related Articles | Metrics

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Subcellular localization of alpha-synuclein aggregates and their interaction with membranes Fabiana Miraglia, Alessio Ricci, Lucia Rota, Emanuela Colla 2018, 13 (7):  1136-1144.  doi: 10.4103/1673-5374.235013 Abstract ( 147 )   PDF (618KB) ( 295 )   Save For more than a decade numerous evidence has been reported on the mechanisms of toxicity of α-synuclein (αS) oligomers and aggregates in α-synucleinopathies. These species were thought to form freely in the cytoplasm but recent reports of αS multimer conformations when bound to synaptic vesicles in physiological conditions, have raised the question about where αS aggregation initiates. In this review we focus on recent literature regarding the impact on membrane binding and subcellular localization of αS toxic species to understand how regular cellular function of αS contributes to pathology. Notably αS has been reported to mainly associate with specific membranes in neurons such as those of synaptic vesicles, ER/Golgi and the mitochondria, while toxic species of αS have been shown to inhibit, among others, neurotransmission, protein trafficking and mitochondrial function. Strategies interfering with αS membrane binding have shown to improve αS-driven toxicity in worms and in mice. Thus, a selective membrane binding that would result in a specific subcellular localization could be the key to understand how aggregation and pathology evolves, pointing out to αS functions that are primarily affected before onset of irreversible damage. Related Articles | Metrics

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Glaucomatous optic neuropathy treatment options: the promise of novel therapeutics, techniques and tools to help preserve vision Najam A. Sharif 2018, 13 (7):  1145-1150.  doi: 10.4103/1673-5374.235017 Abstract ( 129 )   PDF (912KB) ( 376 )   Save Peripheral vision loss followed by “tunnel vision” and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells (RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve. Since patients suffering from this glaucomatous optic neuropathy (GON) first notice visual impairment when they have lost > 40% of their RGCs, early diagnosis is the key to retard the progression of glaucoma. Elevated intraocular pressure (IOP), low cerebrospinal and/or low intracranial fluid pressure, advancing age, and ethnicity are major risk factors associated with POAG. However, retinal vascular abnormalities, a high sensitivity of RGCs and optic nerve head components to neurotoxic, inflammatory, oxidative and mechanical insults also contribute to vision loss in POAG/GON. Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs and combination drug products. Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/ NTG. Neuroprotective and regenerative agents, coupled with electroceutical, mechanical support systems, stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON. The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures, thereby providing a gain of function of the visual system for the glaucoma patients. Related Articles | Metrics

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Factors that modulate olfactory dysfunction Kate Beecher, James A. St John, Fatemeh Chehrehasa 2018, 13 (7):  1151-1155.  doi: 10.4103/1673-5374.235018 Abstract ( 126 )   PDF (714KB) ( 290 )   Save The olfactory system is one of a few areas in the nervous system which is capable of regeneration throughout the life. Olfactory sensory neurons reside in the nasal cavity are continuously replenished with new neurons arising from stem cells. Some factors such as aging, neurodegenerative diseases, head trauma, brain tumor extraction and infection cause olfactory dysfunction which significantly influences physical wellbeing, quality of life, mental health, nutritional status, memory processes, identifying danger and is associated with increased mortality. Therefore, finding a treatment to improve olfactory dysfunction is needed. Recent research efforts in the field have shown some very promising new approaches to treat olfactory dysfunction. This review explores the current studies that have addressed therapeutic approaches to improve olfactory neuron regeneration based on cell transplantation therapy, modulation of physiological olfactory dysfunction and drug treatments. Related Articles | Metrics

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What can computational modeling offer for studying the Ca2+ dysregulation in Alzheimer’s disease: current research and future directions Jingyi Liang, Don Kulasiri 2018, 13 (7):  1156-1158.  doi: 10.4103/1673-5374.235020 Abstract ( 129 )   PDF (127KB) ( 255 )   Save Ca2+ dysregulation is an early event observed in Alzheimer’s disease (AD) patients preceding the presence of its clinical symptoms. Dysregulation of neuronal Ca2+ will cause synaptic loss and neuronal death, eventually leading to memory impairments and cognitive decline. Treatments targeting Ca2+ signaling pathways are potential therapeutic strategies against AD. The complicated interactions make it challenging and expensive to study the underlying mechanisms as to how Ca2+ signaling contributes to the pathogenesis of AD. Computational modeling offers new opportunities to study the signaling pathway and test proposed mechanisms. In this mini-review, we present some computational approaches that have been used to study Ca2+ dysregulation of AD by simulating Ca2+ signaling at various levels. We also pointed out the future directions that computational modeling can be done in studying the Ca2+ dysregulation in AD. Related Articles | Metrics

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Molecular mechanism of noradrenaline during the stress-induced major depressive disorder Kenjiro Seki, Satomi Yoshida, Manoj Kumar Jaiswal 2018, 13 (7):  1159-1169.  doi: 10.4103/1673-5374.235019 Abstract ( 162 )   PDF (642KB) ( 394 )   Save Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate. Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression. Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder (MDD) and several antidepressants functions by increasing the monoamine level at the synapses in the brain. However, it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant. Contrary to noradrenergic receptor stimulation, it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant. In addition, enhanced noradrenaline (NA) release is central response to stress and thought to be a risk factor for the development of MDD. Moreover, fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus (LC). However, it is unclear how they alter the firing activity of LC neurons. These inconsistent reports about antidepressant effect of NA-reuptake inhibitors (NRIs) and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD. In this review, we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD. We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons, hypothalamic-pituitary-adrenal axis (HPA-axis) and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD. Related Articles | Metrics

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Amyloid β and free heme: bloody new insights into the pathogenesis of Alzheimer’s disease Jörg Flemmig, Marcel Zámocký, A Alia 2018, 13 (7):  1170-1174.  doi: 10.4103/1673-5374.235021 Abstract ( 162 )   PDF (1374KB) ( 279 )   Save The cerebral formation of Amyloid β (Aβ) is a critical pathological feature of Alzheimer’s disease (AD). An accumulation of this peptide as senile plaques (SP) was already reported by Alois Alzheimer, the discoverer of the disease. Yet the exact contribution of Aβ to AD development remains elusive. Moreover, while extensive cerebral Aβ formation leads to fibril formation in many species, AD-like symptoms apparently depend on the highly conserved N-terminal residues R5, Y10 and H13. The amino acids were also shown to lead to the formation of Aβ-heme complexes, which exhibit peroxidase activity in the presence of H2O2. Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology. Furthermore, Aβ is also known to lead to cerebral micro-vessel destruction (CAA) as well as to hemolytic events. Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes. Related Articles | Metrics

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Matricellular proteins as possible biomarkers for early brain injury after aneurysmal subarachnoid hemorrhage Hidenori Suzuki, Hirofumi Nishikawa, Fumihiro Kawakita 2018, 13 (7):  1175-1178.  doi: 10.4103/1673-5374.235022 Abstract ( 125 )   PDF (326KB) ( 308 )   Save Aneurysmal subarachnoid hemorrhage remains devastating, and the most important determinant of poor outcome is early brain injury (EBI). In clinical settings, as a surrogate marker of EBI, loss of consciousness at ictus, poor initial clinical grades, and some radiographic findings are used, but these markers are somewhat subjective. Thus, it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications. In our opinion, an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia (DCI), being a therapeutic target, and can be measured easily in the peripheral blood in an acute stage. A good candidate of such a biomarker is a matricellular protein, which is a secreted, inducible and multifunctional extracellular matrix protein. There are many kinds of matricellular proteins reported, but only tenascin-C, osteopontin, galectin-3 and periostin are reported relevant to EBI and DCI. Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI, and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI. This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted. Related Articles | Metrics

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Optimization of nanofiber scaffold properties towards nerve guidance channel design Graham Ka-Hon Shea, Francis Mok 2018, 13 (7):  1179-1180.  doi: 10.4103/1673-5374.235023 Abstract ( 137 )   PDF (262KB) ( 251 )   Save Nerve guidance channels are limited by lack of topographical guidance: Treatment of sizeable nerve gaps remains problematic following peripheral nerve injury. Functional outcomes are good when neurorrhaphy, or direct end-to-end suture repair, is possible.The problem arises when there is significant segmental loss, which can occur following trauma as well as oncological procedures. In such scenarios, it is often not possible to appose severed nerve ends without causing significant tension. The current gold standard for management is to utilize autologous nerve grafts, commonly obtained from the sural nerve, to bridge these defects. This inevitably results in loss of cutaneous sensation over the lower limb, and the risk of donor site morbidities including infection and scarring.Suitable donor nerves remain finite in supply, and are often not ideally matched with recipient sites in terms of calibre and length.Nerve guidance channels have been designed to address these limitations, with proximal and distal nerve stumps telescoped and sutured to the ends of the artificial conduit during operative repair.Design objectives of nerve guidance channels have evolved over time with the emergence of new materials. Silicone represents a first-generation channel utilized to restore continuity and to prevent fibrous ingrowth from surrounding tissues. In being non-resorbable, silicone tubes frequently had to be removed as they caused extrinsic compression, offsetting their usefulness despite promising functional recovery. Thus, second-generation conduits shifted towards usage of biodegradable materials. These include commercially available products composed of collagen (Neuragen, Neuroflex, NeuroMatrix), polyglycolic acid (Neurotube),polylactide-caprolactone (Neurolac) and polyvinylalcohol-based hydrogel (SaluTunnel). It is essential that the next generation of guidance channels can facilitate repair across larger nerve gaps, with 2 cm representing a critical threshold beyond which the performance of artificial conduits remains fair. The present generation of nerve guidance channels are lacking in microstructure to provide physical guidance of the regenerative process. Provision of nanotopography within the channel lumen serves to minimize aberrant sprouting, and potentially enhance regeneration along the intended axis. Related Articles | Metrics

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Vascular endothelial growth factor: an essential neurotrophic factor for motoneurons? Paula M. Calvo, Angel M. Pastor, Rosa R. de la Cruz 2018, 13 (7):  1181-1182.  doi: 10.4103/1673-5374.235024 Abstract ( 136 )   PDF (260KB) ( 312 )   Save Vascular endothelial growth factor (VEGF), an angiogenic factor with neuroprotective effects: The VEGF was initially characterized by its vasculogenic and angiogenic activities and its capacity to promote vascular permeability. VEGF is also known as VEGF-A and is the prototype member of a related group of five trophic factors,VEGF-B, VEGF-C, VEGF-D and placental growth factor . Interestingly, VEGF-B shares a high degree of homology with VEGF but, in contrast to VEGF, has low angiogenic activity and is not pro-inflammatory. VEGF-A binds to two tyrosine quinase receptors,named VEGFR-1 and VEGFR-2, and also to the coreceptor neuropilin-1.By contrast, VEGF-B only binds to the tyrosine kinase receptor VEGFR-1 and also to the coreceptor neuropilin-1. Related Articles | Metrics

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Bone morphogenetic protein signaling: a promising target for white matter protection in perinatal brain injury Jill Chang, Robert W. Dettman, Maria L.V. Dizon 2018, 13 (7):  1183-1184.  doi: 10.4103/1673-5374.235025 Abstract ( 108 )   PDF (289KB) ( 278 )   Save Prematurely born newborns, as well as those born at term, may suffer from several types of brain injury including hypoxic-ischemic injury, intracranial hemorrhage, both intraventricular and parenchymal, and injury that is the consequence of intrauterine growth restriction (IUGR). Injury of all types can impact the motor and cognitive abilities of survivors. The mechanisms leading to disability are not completely understood. Here we discuss the role of the bone morphogenetic protein (BMP) signaling pathway in newborn brain injury. We review the evidence that the BMP signaling pathway is activated in various injury types and discuss the downstream effects of its activation and possible interventions to curtail the effects of this pathway’s activation. In addition, we identify interactions with other signaling pathways important in neurodevelopment. Related Articles | Metrics

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Neurodegenerative diseases are a function of matrix breakdown: how to rebuild extracellular matrix and intracellular matrix Greg Maguire 2018, 13 (7):  1185-1186.  doi: 10.4103/1673-5374.235026 Abstract ( 168 )   PDF (459KB) ( 386 )   Save Matrix within cells, the cytoskeleton, and that which surrounds cells,the extracellular matrix (ECM), are connected to one another through a number of receptors including those in primary cilia, serving as an important chemical and physical signaling system: Mechanical forces generated through the matrix play a critical role in determining the form and function of tissues. Such forces, even in adult tissues, will be important given that breakdown of the ECM in adults may lead to the tissue changing from an adult phenotype to one of primordial or embryonic. As an example, chemical and mechanical signaling from the microenvironment and ECM to the cell can be so powerful as to change cellular phenotype from one of cancer to a normal somatic form. Even in development and inheritance, the matrix is important for what embryos receive from egg and sperm upon fertilization. Centrioles, the matrix structures responsible for cell division, are given by the paternal gamete. In the oocytes, the maternal gametes, the centriole is lost through desolvation.Thus, paternal matrix inheritance through the centriole structure is another important example of mechanism of heredity beyond the genome that may have consequences to neural dysfunction. Related Articles | Metrics

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Brain repair for Parkinson’s disease:is the answer in the matrix? Niamh Moriarty, Eilís Dowd 2018, 13 (7):  1187-1188.  doi: 10.4103/1673-5374.235027 Abstract ( 149 )   PDF (586KB) ( 517 )   Save Two hundred years after James Parkinson first described the cardinal motor symptoms of the disorder that would later bear his name, there is still an irrefutable need for a therapy that targets the underlying pathophysiology of the disease and not solely its symptoms. Parkinson’s disease (PD) is classically characterised by Lewy body formation and a relatively selective degeneration of nigrostriatal dopaminergic neurons. The loss of dopaminergic neurons from the substantia nigra pars compacta causes a consequential depletion of the neurotransmitter dopamine from the striatum, and it is this loss that causes the motor symptoms experienced by patients.To date, all treatments for this condition are symptomatic in that they simply endeavour to correct the neurochemical and/or electrical anomalies caused by striatal dopaminergic deafferentation in an attempt to improve motor function. While such symptomatic approaches show extraordinary efficacy in the early years after initiating treatment, the underlying disease pathology continues to progress, and eventually their efficacy subsides. In view of this, there remains an urgent need for an alternative treatment approach that is capable of protecting or repairing the brain in order to provide a more sustained benefit to patients. Related Articles | Metrics

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Developing biomarkers for neurodegenerative diseases using genetically-modified common marmoset models Ikuo Tomioka, Yoshitaka Nagai, Kazuhiko Seki 2018, 13 (7):  1189-1190.  doi: 10.4103/1673-5374.235028 Abstract ( 145 )   PDF (238KB) ( 326 )   Save Mouse and non-human primate models of neurodegenerative disease: The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60. Although the difficulties associated with neurodegenerative diseases present an urgent global issue, there is no effective treatment for these conditions. To develop therapeutic methods and therapeutic agents for neurodegenerative diseases, model animals that simulate the human disease pathology are eagerly anticipated.There have been significant advancement in embryonic stem cell and genetic engineering in mice, and various transgenic models of neurodegenerative diseases provided great contribution to our understanding of basic disease mechanisms and the development of potential therapeutic molecules for neurodegenerative diseases. However, differences between humans and rodents in the structure and physiological functions of the brain have resulted in difficulty in reproducing the selective vulnerability of specific neurons or circuits in mouse and rat models . Non-human primates, on the other hand, more closely share genetic, physiological, and morphological similarities with humans and can provide a better test system for drug and biomarker discovery for various psychological disorders and neurological diseases. Despite their value, non-human primates are not widely used due to limited availability of the animals, requiring a large breeding space, specialized breeders and veterans, which increases the cost of the study, not to mention the ethical issues. Related Articles | Metrics

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Histone methylation in Huntington’s disease: are bivalent promoters the critical targets? Nóra Zsindely, László Bodai 2018, 13 (7):  1191-1192.  doi: 10.4103/1673-5374.235029 Abstract ( 176 )   PDF (298KB) ( 229 )   Save Huntington’s disease (HD) is a currently incurable, late onset, progressive,ultimately fatal neurological disorder (Bates et al., 2015). We have recently published the results of comprehensive genetic interaction tests aimed at identification of histone methyltransferases and demethylases involved in HD pathogenesis in a Drosophila model of the disease.The methylation state of histone proteins regulates the accessibility of chromatin structure by which it may influence transcriptional dysregulation observed in HD. We found that several factors affecting the methylation state of histone H3 lysine 4 (H3K4) and H3K27 residues influenced HD symptoms and identified the H3K27 specific demethylase, Utx, as a druggable target whose inhibition ameliorated neurodegeneration.These results in combination with previous findings suggest that bivalent chromatin regions, which are characterized by simultaneous presence of activating trimethylated-H3K4 (H3K4me3) and repressing H3K27me3 chromatin marks, might play a prominent role in HD pathogenesis. Related Articles | Metrics

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Lateral olfactory tract usher substance (LOTUS) protein, an endogenous Nogo receptor antagonist, converts a non-permissive to permissive brain environment for axonal regrowth Tomoko Hirokawa, Kohtaro Takei 2018, 13 (7):  1193-1194.  doi: 10.4103/1673-5374.235030 Abstract ( 124 )   PDF (220KB) ( 304 )   Save It is well known that primates, including humans, hardly recover motor function after spinal cord injury (SCI) when compared with non-primate mammals such as rodents. This limited functional recovery is in part due to a non-permissive environment of the central nervous system (CNS) inhibiting axonal regrowth. This inhibitory environment for axonal regrowth is mainly caused by interaction of axon growth inhibitors with their common receptor, Nogo receptor-1 (NgR1). Axon regrowth inhibitors such as Nogo proteins, myelin associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and B lymphocyte stimulator (BLyS) are derived from glial cells in damaged brain. Related Articles | Metrics

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Houshiheisan and its components promote axon regeneration after ischemic brain injury Yue Lu, Flora Hsiang, Jia-Hui Chang, Xiao-Quan Yao, Hui Zhao, Hai-Yan Zou, Lei Wang, Qiu-Xia Zhang 2018, 13 (7):  1195-1203.  doi: 10.4103/1673-5374.235031 Abstract ( 286 )   PDF (9599KB) ( 260 )   Save Houshiheisan, a classic prescription in traditional Chinese medicine, contains Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi,Rhizoma Chuanxiong, Radix et Rhizoma Asari, Radix Platycodonis, Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis, Radix et Rhizoma Ginseng, Radix Scutellariae and Concha Ostreae. According to traditional Chinese medicine theory, Flos Chrysanthemi, Radix Saposhnikoviae, Ramulus Cinnamomi, Rhizoma Chuanxiong, Radix et Rhizoma Asari and Radix Platycodonis are wind-dispelling drugs; Rhizoma Atractylodis macrocephalae, Poria, Rhizoma Zingiberis, Radix Angelicae sinensis and Radix et Rhizoma Ginseng are deficiency-nourishing drugs. A large number of randomized controlled trials have shown that Houshiheisan is effective in treating stroke, but its mechanism of action is unknown. Axonal remodeling is an important mechanism in neural protection and regeneration. Therefore, this study explored the effect and mechanism of action of Houshiheisan on the repair of axons after cerebral ischemia. Rat models of focal cerebral ischemia were established by ligating the right middle cerebral artery. At 6 hours after model establishment, rats were intragastrically administered 10.5 g/kg Houshiheisan or 7.7 g/kg wind-dispelling drug or 2.59 g/kg deficiency-nourishing drug. These medicines were intragastrically administered as above every 24 hours for 7 consecutive days. Houshiheisan,and its wind-dispelling and deficiency-nourishing components reduced the neurological deficit score and ameliorated axon and neuron lesions after cerebral ischemia. Furthermore, Houshiheisan, and its wind-dispelling and deficiency-nourishing components decreased the expression of proteins that inhibit axonal remodeling: amyloid precursor protein, neurite outgrowth inhibitor protein A (Nogo-A), Rho family small GTPase A (RhoA) and Rho-associated kinase 2 (Rock2), and increased the expression of growth associated protein-43, microtubule-associated protein-2, netrin-1, Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42). The effect of Houshiheisan was stronger than wind-dispelling drugs or deficiency-nourishing drugs alone. In conclusion, Houshiheisan, and wind-dispelling and deficiency-nourishing drugs promote the repair of axons and nerve regeneration after cerebral ischemia through Nogo-A/RhoA/Rock2 and Netrin-1/Rac1/Cdc42 signaling pathways. These effects are strongest with Houshiheisan. Related Articles | Metrics

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Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro Pei-Dong Zheng, Rajneesh Mungur, Heng-Jun Zhou, Muhammad Hassan, Sheng-Nan Jiang, Jie-Sheng Zheng 2018, 13 (7):  1204-1211.  doi: 10.4103/1673-5374.232476 Abstract ( 166 )   PDF (1776KB) ( 288 )   Save Neural stem cells have great potential for the development of novel therapies for nervous system diseases. However, the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair. Ginkgolide B has a robust neuroprotective effect. In this study, we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo. Neural stem cells were treated with 20, 40 and 60 mg/L ginkgolide B in vitro. Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase, glial fibrillary acid protein and suppressor of cytokine signaling 2. After treatment with 40 and 60 mg/L ginkgolide B, cells were large, with long processes. Moreover, the proportions of neuron-specific enolase-, glial fibrillary acid protein- and suppressor of cytokine signaling 2-positive cells increased. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. Six hours after ischemia, ginkgolide B (20 mg/kg) was intraperitoneally injected, once a day. Zea Longa’s method was used to assess neurological function. Immunohistochemistry was performed to evaluate the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells. Real-time quantitative polymerase chain reaction was used to measure mRNA expression of brain-derived neurotrophic factor and epidermal growth factor. Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2. Ginkgolide B decreased the neurological deficit score, increased the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells, increased the mRNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together, the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury. Related Articles | Metrics

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Is transesophageal echocardiography needed for evaluating tissue-based transient ischemic attack? Mohamed Al-Khaled, Björn Scheef, Toralf Brüning 2018, 13 (7):  1212-1215.  doi: 10.4103/1673-5374.235058 Abstract ( 132 )   PDF (160KB) ( 227 )   Save Transient ischemic attack (TIA) is a warning signal for stroke. A comprehensive evaluation of TIA may reduce the risk for subsequent stroke. Data on the findings of cardiac evaluation with transesophageal echocardiography (TEE) in patients with TIA are sparse. Our aims were to determine the frequency of TEE performance and to investigate the findings of TEE in patients with TIA based on the new definition of TIA (i.e., transient neurological symptoms without evidence of infarction). During a 4-year period (2011–2014), 1071 patients (mean age, 70 ± 13 years; female, 49.7%) with TIA were included in a prospective study and evaluated. Of 1071 consecutive patients suffering from TIA, 288 patients (27%) underwent TEE.The median time between admission and TEE was 6 days. Patients with TIA who were evaluated by TEE were younger (67 vs. 71 years, P < 0.001) than those who were not evaluated by TEE. They had a higher rate of sensibility disturbance as a TIA symptom (39% vs. 31%, P = 0.012) but a lower rate of previous stroke (15% vs. 25%, P = 0.001) and atrial fibrillation (2% vs. 21%, P < 0.001) than those who did not. Foramen ovale was detected in 71 patients (25.7%), atrial septal aneurysm in 13 patients (4.6%), and severe atherosclerotic plaques (grade 4 and 5) in the aortic arch in 25 patients (8.7%). One patient (0.3%) had a fibroma detected by TEE. In 17 of the 288 patients (6%) who underwent TEE, the indication for anticoagulation therapy was based on the TEE results, and 1 patient with fibroma underwent heart surgery. During hospitalization,7 patients experienced a subsequent stroke, and 27 patients had a recurrent TIA. At 3 months following discharge, the rates of readmission, stroke, recurrent TIA, and death were 19%, 2.7%, 4.2%, and 1.6%, respectively. The rates of mortality (0.9% vs. 1.8%, P = 0.7), stroke risk (1.9% vs. 3.0%, P = 0.8), and recurrent TIA (5.0% vs. 3.9%, P = 0.8) were similar in patients who underwent TEE and in those who did not. Performing TEE in patients with tissue-based TIA is helpful in detecting cardiac sources for embolism and may indicate for anticoagulation. Related Articles | Metrics

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MicroRNA-219 alleviates glutamate-induced neurotoxicity in cultured hippocampal neurons by targeting calmodulin-dependent protein kinase II gamma Ting Wang, Qun Cai, Wen-Jie Yang, Hai-Hua Fan, Jian-Feng Yi, Feng Xu 2018, 13 (7):  1216-1224.  doi: 10.4103/1673-5374.235059 Abstract ( 143 )   PDF (802KB) ( 338 )   Save Septic encephalopathy is a frequent complication of sepsis, but there are few studies examining the role of microRNAs (miRs) in its pathogenesis.In this study, a miR-219 mimic was transfected into rat hippocampal neurons to model miR-219 overexpression. A protective effect of miR-219 was observed for glutamate-induced neurotoxicity of rat hippocampal neurons, and an underlying mechanism involving calmodulin-dependent protein kinase II γ (CaMKIIγ) was demonstrated. miR-219 and CaMKIIγ mRNA expression induced by glutamate in hippocampal neurons was determined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). After neurons were transfected with miR-219 mimic, effects on cell viability and apoptosis were measured by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. In addition, a luciferase reporter gene system was used to confirm CaMKIIγ as a target gene of miR-219. Western blot assay and rescue experiments were also utilized to detect CaMKIIγ expression and further verify that miR-219 in hippocampal neurons exerted its effect through regulation of CaMKIIγ. MTT assay and qRT-PCR results revealed obvious decreases in cell viability and miR-219 expression after glutamate stimulation, while CaMKIIγ mRNA expression was increased. MTT,flow cytometry, and caspase-3 activity assays showed that miR-219 overexpression could elevate glutamate-induced cell viability, and reduce cell apoptosis and caspase-3 activity. Moreover, luciferase CaMKIIγ-reporter activity was remarkably decreased by co-transfection with miR-219 mimic, and the results of a rescue experiment showed that CaMKIIγ overexpression could reverse the biological effects of miR-219. Collectively, these findings verify that miR-219 expression was decreased in glutamate-induced neurons, CaMKIIγ was a target gene of miR-219, and miR-219 alleviated glutamate-induced neuronal excitotoxicity by negatively controlling CaMKIIγ expression. Related Articles | Metrics

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Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex, but not in the myocardium Wen-Yuan Zhang, Ke-Yi Wang, Yun-Jing Li, Ying-Ran Li, Rong-Zhi Lu 2018, 13 (7):  1225-1230.  doi: 10.4103/1673-5374.235060 Abstract ( 145 )   PDF (734KB) ( 275 )   Save Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson’s correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover,4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex. Related Articles | Metrics

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A partition-type tubular scaffold loaded with PDGFreleasing microspheres for spinal cord repair facilitates the directional migration and growth of cells Xue Chen, Mei-Ling Xu, Cheng-Niu Wang, Lu-Zhong Zhang, Ya-Hong Zhao, Chang-Lai Zhu, Ying Chen, Jian Wu, Yu-Min Yang, Xiao-Dong Wang 2018, 13 (7):  1231-1240.  doi: 10.4103/1673-5374.235061 Abstract ( 189 )   PDF (2351KB) ( 391 )   Save The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ. Platelet-derived growth factor (PDGF) has been shown to promote the migration of bone marrow stromal cells;however, cytokines need to be released at a steady rate to maintain a stable concentration in vivo. Therefore, new methods are needed to maintain an optimal concentration of cytokines over an extended period of time to effectively promote seed cell localization, proliferation and differentiation. In the present study, a partition-type tubular scaffold matching the anatomical features of the thoracic 8–10 spinal cord of the rat was fabricated using chitosan and then subsequently loaded with chitosan-encapsulated PDGF-BB microspheres (PDGF-MSs).The PDGF-MS-containing scaffold was then examined in vitro for sustained-release capacity, biocompatibility, and its effect on neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells (MUSE-NPCs). We found that pre-freezing for 2 hours at −20°C significantly increased the yield of partition-type tubular scaffolds, and 30 μL of 25% glutaraldehyde ensured optimal crosslinking of PDGF-MSs. The resulting PDGF-MSs cumulatively released 52% of the PDGF-BB at 4 weeks in vitro without burst release.The PDGF-MS-containing tubular scaffold showed suitable biocompatibility towards MUSE-NPCs and could promote the directional migration and growth of these cells. These findings indicate that the combination of a partition-type tubular scaffold, PDGF-MSs and MUSENPCs may be a promising model for the fabrication of tissue-engineered spinal cord grafts. Related Articles | Metrics

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Effects of decompression joint Governor Vessel electro-acupuncture on rats with acute upper cervical spinal cord injury Yan-Lei Wang, Ying-Na Qi, Wei Wang, Chun-Ke Dong, Ping Yi, Feng Yang, Xiang-Sheng Tang, Ming-Sheng Tan 2018, 13 (7):  1241-1246.  doi: 10.4103/1673-5374.235062 Abstract ( 156 )   PDF (602KB) ( 274 )   Save Decompression is the major therapeutic strategy for acute spinal cord injury, but there is some debate about the time window for decompression following spinal cord injury. An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury. Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord. In this study, Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury. The rat models were established by inserting a balloon catheter into the atlanto-occipital space. The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression. Electroacupuncture was conducted at the acupoints Dazhui (GV14) and Baihui (GV 20) (2 Hz, 15 minutes) once a day for 14 consecutive days.Compared with decompression alone, hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture. However, the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours. Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone. These findings indicate that compared with decompression alone,Governor Vessel electroacupuncture combined with delayed decompression (48 hours) is more effective in the treatment of upper cervical spinal cord injury. Governor Vessel electroacupuncture combined with early decompression (12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury. Nevertheless, further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone Related Articles | Metrics

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Controlled release of FK506 from micropatterned PLGA films: potential for application in peripheral nerve repair Brett Davis, Susan Wojtalewicz, Pratima Labroo, Jill Shea, Himanshu Sant, Bruce Gale, Jayant Agarwal 2018, 13 (7):  1247-1252.  doi: 10.4103/1673-5374.235063 Abstract ( 146 )   PDF (1083KB) ( 358 )   Save After decades of research, peripheral nerve injury and repair still frequently results in paralysis, chronic pain and neuropathies leading to severe disability in patients. Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506 (Tacrolimus), an FDA approved immunosuppressant, has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically. The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves. Photolithography was used to create micropatterned poly(lactide-co-glycolic acid) (PLGA) films embedded with FK506. Non-patterned,10/10 μm (ridge/groove width), and 30/30 μm patterned films loaded with 0, 1, and 3 μg/cm2 FK506 were manufactured and characterized. In vitro FK506 rate of release testing indicated that the films are capable of an extended (at least 56 days), controlled, and scalable release of FK506. Neurite extension bioactivity assay indicated that FK506 released from the films (concentration of samples tested ranged between 8.46–19.7 ng/mL) maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages (10 ng/mL FK506). The multi-functional FK506 embedded, micropatterned poly(lactide-co-glycolic acid) films developed in this study have potential to be used in the construction of peripheral nerve repair devices. Related Articles | Metrics

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Spatiotemporal microRNA profile in peripheral nerve regeneration: miR-138 targets vimentin and inhibits Schwann cell migration and proliferation Travis B. Sullivan, Litchfield C. Robert, Patrick A. Teebagy, Shannon E. Morgan, Evan W. Beatty, Bryan J. Cicuto, Peter K. Nowd,Kimberly M. Rieger-Christ, David J. Bryan 2018, 13 (7):  1253-1262.  doi: 10.4103/1673-5374.235073 Abstract ( 170 )   PDF (1777KB) ( 524 )   Save While the peripheral nervous system has regenerative ability, restoration of sufficient function remains a challenge. Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneration,including myelination, neuroplasticity, kinase signaling in nerve axoplasm, and cell migration;however, the mechanisms regulating its expression within Schwann cell (SC) remain unexplored. The aim of this study was to profile the spatial and temporal expression profile of microRNA (miRNA) in a regenerating rat sciatic nerve after transection, and explore the potential role of miR-138-5p targeting vimentin in SC proliferation and migration. A rat sciatic nerve transection model, utilizing a polyethylene nerve guide,was used to investigate miRNA expression at 7, 14, 30, 60, and 90 days during nerve regeneration. Relative levels of miRNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain reaction. In vitro assays were conducted with cultured Schwann cells transfected with miRNA mimics and assessed for migratory and proliferative potential. The top seven dysregulated miRNAs reported in this study have been implicated in cell migration elsewhere, and GO and KEGG analyses predicted activities essential to wound healing. Transfection of one of these, miRNA-138-5p, into SCs reduced cell migration and proliferation. miR-138-5p has been shown to directly target vimentin in cancer cells, and the luciferase assay performed here in rat Schwann cells confirmed it. These results detail a role of miR-138-5p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system. Related Articles | Metrics

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Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury Heng-Tao Xie, Zhong-Yuan Xia*, Xia Pan, Bo Zhao, Zhi-Gang Liu 2018, 13 (7):  1263-1268.  doi: 10.4103/1673-5374.235074 Abstract ( 204 )   PDF (468KB) ( 306 )   Save Puerarin is a major active ingredient of the traditional Chinese plant medicine, Radix Puerariae, and commonly used in the treatment of myocardial and cerebral ischemia. However, the effects of puerarin on neuropathic pain are still unclear. In this study, a neuropathic pain animal model was created by partial sciatic nerve ligation. Puerarin (30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment. Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats, especially at 7 days after model establishment.At 7 days after model establishment, quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed mRNA expression of transient receptor potential vanilloid 1 (Trpv1) and transient receptor potential ankyrin 1 (Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury. These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats. Related Articles | Metrics

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Zishenpingchan granules for the treatment of Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial Qing Ye, Xiao-Lei Yuan, Can-Xing Yuan, Hong-Zhi Zhang, Xu-Ming Yang 2018, 13 (7):  1269-1275.  doi: 10.4103/1673-5374.235075 Abstract ( 650 )   PDF (411KB) ( 445 )   Save Levodopa preparations remain the preferred drug for Parkinson’s disease. However, long-term use of levodopa may lead to a series of motor complications. Previous studies have shown that the combination of levodopa and Zishenpingchan granules (consisting of Radix Rehmanniae preparata, Lycium barbarum, Herba Taxilli, Rhizoma Gastrodiae, Stiff Silkorm, Curcuma phaeocaulis, Radix Paeoniae Alba,Rhizoma Arisaematis, Scorpio and Centipede) can markedly improve dyskinesia and delay the progression of Parkinson’s disease, with especially dramatic improvements of non-motor symptoms. However, the efficacy of this combination has not been confirmed by randomized controlled trials. The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register (registration number: ChiCTR-INR-1701194). From December 2014 to December 2016, 128 patients (72 males and 56 females, mean age of 65.78 ± 6.34 years) with Parkinson’s disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China. Patients were equally allocated into treatment and control groups. In addition to treatment with dopamine, patients in treatment and control groups were given Zishenpingchan granules or placebo, respectively, for 24 weeks. Therapeutic efficacy was assessed using the Unified Parkinson’s Disease Rating Scale,on-off phenomenon, Hoehn-Yahr grade, Scales for Outcomes in Parkinson’s disease–Autonomic, Parkinson’s disease sleep scale, Hamilton Anxiety Scale, Hamilton Depression Scale, Mini-Mental State Examination, and the Parkinson’s Disease Quality of Life Questionnaire.Artificial neural networks were used to determine weights at which to scale these parameters. Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications, and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson’s disease. This combination of Chinese and Western medicine has the potential to reduce levodopa dosages, and no obvious side effects were found. These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson’s disease,reduce toxic side effects of dopaminergic agents, and exert synergistic and detoxifying effects. Related Articles | Metrics

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Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson’s disease models Lan-Xiang Liu, Dan Du, Zhan-Qiu Wang, Yuan Fang, Tao Zheng, Yan-Chao Dong, Qing-Lei Shi, Min Zhao, Fang Xiao, Juan Du 2018, 13 (7):  1276-1280.  doi: 10.4103/1673-5374.235076 Abstract ( 186 )   PDF (736KB) ( 268 )   Save Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson’s disease animal models. They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra, but also satisfy the requirements for iron deposition. However, few studies have compared the characteristics of these two models by magnetic resonance imaging. In this study, rat models of Parkinson’s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra. At 1, 2, 4, and 6 weeks after injection, coronal whole-brain T2-weighted imaging, transverse whole-brain T2-weighted imaging, and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2* values at the injury site. The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group. In the 6-hydroxydopamine group,the fractional anisotropy value was decreased, but T2* values were increased on the right side of the substantia nigra at 1 week. Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods, while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson’s disease over long periods. Related Articles | Metrics

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Degree of dopaminergic degeneration measured by 99mTc-TRODAT-1 SPECT/CT imaging Ling Lin, Jing Ye, Han Zhang, Zhong-Fu Han, Zhi-Hong Zheng 2018, 13 (7):  1281-1287.  doi: 10.4103/1673-5374.235077 Abstract ( 196 )   PDF (920KB) ( 282 )   Save To prevent and treat Parkinson’s disease in its early stages, it is essential to be able to detect the degree of early dopaminergic neuron degeneration. Dopamine transporters (DAT) in the striatum regulate synaptic dopamine levels, and striatal 99mTc-TRODAT-1 single-photon  emission computed tomography (-SPECT) imaging is a marker for presynaptic neuronal degeneration. However, the association between the degree of dopaminergic degeneration and in vivo 99mTc-TRODAT-1 SPECT imaging is unknown. Therefore, this study investigated the association between the degree of 6-hydroxydopamine (6-OHDA)-induced dopaminergic degeneration and DAT imaging using 99mTc-TRODAT-1 SPECT in rats. Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA (2, 4, and 8 μg) into the right medial forebrain bundle. The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining. The results showed that striatal 99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups, and that DAT 99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion (r = –0.887, P < 0.01). There were significant correlations between DAT 99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2, 4, and 8 μg 6-OHDA groups at 8 weeks post-lesion (r = 0.899, P < 0.01). These findings indicate that striatal DAT imaging using 99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration. Related Articles | Metrics

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Injury of the superior longitudinal fasciculus by ventriculoperitoneal shunt: a diffusion tensor tractography study Sung Ho Jang, Han Do Lee 2018, 13 (7):  1288-1289.  doi: 10.4103/1673-5374.235093 Abstract ( 157 )   PDF (374KB) ( 279 )   Save In this study, we report on a patient who suffered from injury of the superior longitudinal fasciculus following ventriculoperitoneal (VP) shunt operation, which was demonstrated with diffusion tensor tractography (DTT). Related Articles | Metrics

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Modulation of microglial functions by methyl jasmonate Jordan A. McKenzie, Andis Klegeris 2018, 13 (7):  1290-1293.  Abstract ( 170 )   PDF (190KB) ( 224 )   Save Neuroinflammation contributes to the neurodegenerative processes in Alzheimer’s disease (AD); therefore, characterization of novel drug candidates aimed at combatting inflammation in the central nervous system is one of the potential avenues for the development of effective AD treatment and prevention strategies.Non-neuronal microglial cells orchestrate neuroinflammatory reactions, and their adverse activation has been linked to AD pathogenesis. Methyl jasmonate (MJ) has anti-cancer properties and has also been shown to reduce peripheral inflammation in pre-clinical models. Recently, anti-neuroinflammatory activity of MJ was demonstrated in mice, but the exact cellular and molecular mechanisms responsible for this beneficial effect are unknown. We hypothesized that MJ can regulate select microglial functions, and used two different in vitro models of microglia to test this hypothesis. MJ inhibited the production of damaging reactive oxygen species by differentiated human HL-60 promyelocytic leukemia cells without reducing their viability. MJ also selectively upregulated phagocytic activity of murine BV-2 microglia, but had no effect on nitric oxide secretion by these cells. Since microglial phagocytosis can be beneficial for clearance of amyloid β aggregates in AD, the observed upregulation of phagocytic activity by MJ, combined with its inhibitory effect on reactive oxygen species production, supports continued studies of MJ as a candidate drug for managing adverse neuroinflammation in AD. Related Articles | Metrics

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Stem cells: a promising candidate to treat neurological disorders Chang-Geng Song, Yi-Zhe Zhang, Hai-Ning Wu, Xiu-Li Cao, Chen-Jun Guo, Yong-Qiang Li, Min-Hua Zheng, Hua Han 2018, 13 (7):  1294-1304.  doi: 10.4103/1673-5374.235085 Abstract ( 248 )   PDF (250KB) ( 478 )   Save Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system. Therefore, based on the regenerative capacity of stem cells, transplantation therapies of various stem cells have been tested in basic research and preclinical trials, and some have shown great prospects. This manuscript overviews the cellular and molecular characteristics of embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal stem/progenitor cells, mesenchymal stem/stromal cells,and their derivatives in vivo and in vitro as sources for regenerative therapy. These cells have all been considered as candidates to treat several major neurological disorders and diseases, owing to their self-renewal capacity, multi-directional differentiation, neurotrophic properties, and immune modulation effects. We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and age-related macular degeneration, as well as traumatic brain injury and glioblastoma. In spite of a few unsuccessful cases, risks of tumorigenicity, and ethical concerns, most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease. In summary, these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders.Thus, stem cells are a promising candidate for the treatment of nervous system diseases. Related Articles | Metrics