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15 May 2020, Volume 15 Issue 5 Previous Issue    Next Issue

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Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review Yazdan Naderi, Yunes Panahi, George E. Barreto, Amirhosein Sahebkar 2020, 15 (5):  773-782.  doi: 10.4103/1673-5374.268898 Abstract ( 129 )   PDF (263KB) ( 155 )   Save To review the neuroprotective effects of minocycline in focal cerebral ischemia in animal models. By searching in the databases of PubMed, ScienceDirect, and Scopus, and considering the inclusion and exclusion criteria of the study. Studies were included if focal cerebral ischemia model was performed in mammals and including a control group that has been compared with a minocycline group. Written in languages other than English; duplicate data; in vitro studies and combination of minocycline with other neuroprotective agents were excluded. Neurological function of patients was assessed by National Institute of Health Stroke Scale, modified Rankin Scale, and modified Barthel Index. Neuroprotective effects were assessed by detecting the expression of inflammatory cytokines. We examined 35 papers concerning the protective effects of minocycline in focal cerebral ischemia in animal models and 6 clinical trials which had evaluated the neuroprotective effects of minocycline in ischemic stroke. These studies revealed that minocycline increases the viability of neurons and decreases the infarct volume following cerebral ischemia. The mechanisms that were reported in these studies included anti-inflammatory, antioxidant, as well as anti-apoptotic effects. Minocycline also increases the neuronal regeneration following cerebral ischemia. Minocycline has considerable neuroprotective effects against cerebral ischemia-induced neuronal damages. However, larger clinical trials may be required before using minocycline as a neuroprotective drug in ischemic stroke. Related Articles | Metrics

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Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering Rocío Fernández-Serra, Rebeca Gallego, Paloma Lozano, Daniel González-Nieto 2020, 15 (5):  783-789.  doi: 10.4103/1673-5374.268891 Abstract ( 259 )   PDF (1447KB) ( 287 )   Save The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal pathologies. High-performance preclinical results have failed at clinical level, as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke, Alzheimer’s and Parkinson’s diseases. An unquestionable reality is the current absence of effective therapies to neuroprotect the brain, to arrest neurodegeneration and rewire the impaired brain circuits. Part of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet clarified. Another contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation procedures. For medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last decades. Although the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs, the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown exponentially. Hydrogel-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced therapy. Hydrogels show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and cells. It is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and elongation. Along this article, we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery, cell engraftment and axonal reinnervation in brain pathologies. Related Articles | Metrics

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Edible seaweed-derived constituents: an undisclosed source of neuroprotective compounds Melissa Schepers, Nikita Martens, Assia Tiane, Kenneth Vanbrabant, Hong-Bing Liu, Dieter Lütjohann, Monique Mulder, Tim Vanmierlo 2020, 15 (5):  790-795.  doi: 10.4103/1673-5374.268894 Abstract ( 93 )   PDF (508KB) ( 166 )   Save Edible marine algae, or seaweeds, are a rich source of several bioactive compounds including phytosterols, carotenoids, and polysaccharides. Over the last decades, seaweed-derived constituents turned out to not only reside in the systemic circulation, but are able to cross the blood-brain barrier to exert neuro-active functions both in homeostatic and pathological conditions. Therefore, seaweed-derived constituents have gained increasing interest for their neuro-immunomodulatory and neuroprotective properties, rendering them interesting candidates for the management of several neurodegenerative disorders. In particular seaweed-derived phytosterols gained interest for the treatment of neurodegenerative disorders as they potentiate neuroplasticity, enhance phagocytic clearance of neurotoxic peptides and have anti-inflammatory properties. Though, the anti-inflammatory and anti-oxidative properties of other constituents including carotenoids, phenols and polysaccharides have recently gained more interest. In this review, we provide an overview of a selection of the described neuro-active properties of seaweed-derived constituents with a focus on phytosterols. Related Articles | Metrics

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Exosomes as mediators of neuron-glia communication in neuroinflammation María Pascual, Francesc Ibáñez, Consuelo Guerri 2020, 15 (5):  796-801.  doi: 10.4103/1673-5374.268893 Abstract ( 128 )   PDF (1161KB) ( 171 )   Save In recent years, a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological conditions. These nanovesicles (30–150 nm) contain proteins, RNAs and lipids, and their internalization by bystander cells could alter their normal functions. This review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous system. Special emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain, in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative disorders. Given the small size and characteristics of exosomes, they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and neuropathologies. Finally, although the application potential of exosome is still limited, current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation. Related Articles | Metrics

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Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies Giulia Costa, Maria Antonietta De Luca, Gessica Piras, Jacopo Marongiu, Liana Fattore, Nicola Simola 2020, 15 (5):  802-816.  doi: 10.4103/1673-5374.268895 Abstract ( 148 )   PDF (474KB) ( 156 )   Save Preclinical and clinical studies indicate that synthetic psychoactive substances, in addition to having abuse potential, may elicit toxic effects of varying severity at the peripheral and central levels. Nowadays, toxicity induced by synthetic psychoactive substances poses a serious harm for health, since recreational use of these substances is on the rise among young and adult people. The present review summarizes recent findings on the peripheral and central toxicity elicited by “old” and “new” synthetic psychoactive substances in humans and experimental animals, focusing on amphetamine derivatives, hallucinogen and dissociative drugs and synthetic cannabinoids. Related Articles | Metrics

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Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders Chuan-Jun Zhuo, Wei-Hong Hou, De-Guo Jiang, Hong-Jun Tian, Li-Na Wang, Feng Jia, Chun-Hua Zhou, Jing-Jing Zhu 2020, 15 (5):  817-823.  doi: 10.4103/1673-5374.268969 Abstract ( 109 )   PDF (448KB) ( 199 )   Save Neuropsychiatric disorders represent a set of severe and complex mental illnesses, and the exact etiologies of which are unknown. It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders. Currently, the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment, because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure. In recent years, there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs. In the brain, circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts. They are highly active at neuronal synapses. These features make circRNAs uniquely crucial for understanding brain health, disease, and neuropsychiatric disorders. This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders. In addition, we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders. The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders. Related Articles | Metrics

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Alzheimer’s disease, neural stem cells and neurogenesis: cellular phase at single-cell level Mehmet Ilyas Cosacak, Prabesh Bhattarai, Caghan Kizil 2020, 15 (5):  824-827.  doi: 10.4103/1673-5374.268896 Abstract ( 118 )   PDF (558KB) ( 222 )   Save Alzheimer’s disease cannot be cured as of yet. Our current understanding on the causes of Alzheimer’s disease is limited. To develop treatments, experimental models that represent a particular cellular phase of the disease and more rigorous scrutiny of the cellular pathological mechanisms are crucial. In recent years, Alzheimer’s disease research underwent a paradigm shift. According to this tendency, Alzheimer’s disease is increasingly being conceived of a disease where not only neurons but also multiple cell types synchronously partake to manifest the pathology. Knowledge on every cell type adds an alternative approach and hope for the efforts towards the treatment. Neural stem cells and their neurogenic ability are making an appearance as a new aspect of the disease manifestation based on the recent findings that neurogenesis reduces dramatically in Alzheimer’s disease patients compared to healthy individuals. Therefore, understanding how neural stem cells can form new neurons in Alzheimer’s disease brains holds an immense potential for clinics. However, this provocative idea requires further evidence and tools for investigation. Recently, single cell sequencing appeared as a revolutionary tool to understand cellular programs in unprecedented resolution and it will undoubtedly facilitate comprehensive investigation of different cell types in Alzheimer’s disease. In this mini-review, we will touch upon recent studies that use single cell sequencing for investigating cellular response in Alzheimer’s disease and some consideration pertaining to the utilization of neural regeneration for Alzheimer’s disease research. Related Articles | Metrics

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Electroencephalography studies of hypoxic ischemia in fetal and neonatal animal models Hamid Abbasi, Charles P. Unsworth 2020, 15 (5):  828-837.  doi: 10.4103/1673-5374.268892 Abstract ( 102 )   PDF (220KB) ( 263 )   Save Alongside clinical achievements, experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE). Due to the reasonably fair degree of flexibility with experiments, most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury, following HI insult. This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents, piglets, sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult. Related Articles | Metrics

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Regional brain susceptibility to neurodegeneration: what is the role of glial cells? Andrea Beatriz Cragnolini, Giorgia Lampitella, Assunta Virtuoso, Immacolata Viscovo, Fivos Panetsos, Michele Papa, Giovanni Cirillo 2020, 15 (5):  838-842.  doi: 10.4103/1673-5374.268897 Abstract ( 106 )   PDF (909KB) ( 145 )   Save The main pathological feature of the neurodegenerative diseases is represented by neuronal death that represents the final step of a cascade of adverse/hostile events. Early in the neurodegenerative process, glial cells (including astrocytes, microglial cells, and oligodendrocytes) activate and trigger an insidious neuroinflammatory reaction, metabolic decay, blood brain barrier dysfunction and energy impairment, boosting neuronal death. How these mechanisms might induce selective neuronal death in specific brain areas are far from being elucidated. The last two decades of neurobiological studies have provided evidence of the main role of glial cells in most of the processes of the central nervous system, from development to synaptogenesis, neuronal homeostasis and integration into, highly specific neuro-glial networks. In this mini-review, we moved from in vitro and in vivo models of neurodegeneration to analyze the putative role of glial cells in the early mechanisms of neurodegeneration. We report changes of transcriptional, genetic, morphological, and metabolic activity in astrocytes and microglial cells in specific brain areas before neuronal degeneration, providing evidence in experimental models of neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Understanding these mechanisms might increase the insight of these processes and pave the way for new specific glia-targeted therapeutic strategies for neurodegenerative disorders. Related Articles | Metrics

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Natural stilbenes effects in animal models of Alzheimer’s disease Aline Freyssin, Guylène Page, Bernard Fauconneau, Agnès Rioux Bilan 2020, 15 (5):  843-849.  doi: 10.4103/1673-5374.268970 Abstract ( 112 )   PDF (993KB) ( 196 )   Save Alzheimer’s disease is one of the most frequent neurodegenerative diseases. This pathology is characterized by protein aggregates, mainly constituted by amyloid peptide and tau, leading to neuronal death and cognitive impairments. Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies. However, stilbenes presenting multiple pharmacological effects could be good potential therapeutic candidates. The aim of this review is to gather the more significant papers among the broad literature on this topic, concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer’s disease. Indeed, numerous studies focus on cellular models, but an in vivo approach remains of primary importance since in animals (mice or rats, generally), bioavailability and metabolism are taken into account, which is not the case in in vitro studies. Furthermore, examination of memory ability is feasible in animal models, which strengthens the relevance of a compound with a view to future therapy in humans. This paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in humans. This review shows that resveratrol, the reference polyphenol, is largely studied and seems to have interesting properties on amyloid plaques, and cognitive impairment. However, some resveratrol derivatives such as gnetin C, trans-piceid, or astringin have never been tested on animals. Furthermore, pterostilbene is of particular interest, by its improvement of cognitive disorders and its neuroprotective role. It could be relevant to evaluate this molecule in clinical trials. Related Articles | Metrics

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Neurodegenerative diseases as proteinopathies-driven immune disorders Fausta Ciccocioppo, Giuseppina Bologna, Eva Ercolino, Laura Pierdomenico, Pasquale Simeone, Paola Lanuti, Damiana Pieragostino, Piero Del Boccio, Marco Marchisio, Sebastiano Miscia 2020, 15 (5):  850-856.  doi: 10.4103/1673-5374.268971 Abstract ( 101 )   PDF (1180KB) ( 126 )   Save In the pathophysiology of neurodegenerative disorders, the role of misfolded protein deposition leading to neurodegeneration has been primarily discussed. In the last decade, however, it has been proposed a parallel involvement of innate immune activation, chronic inflammation and adaptive immunity in the neurodegeneration mechanisms triggered by proteinopathies. New insights in the neurodegenerative field strongly suggest a role for the immune system in the pathophysiology of neurodegenerative disorders. Therefore, the hypothesis underlining the modulation of the innate and the adaptive immune system in the events linked to brain deposition of misfolded proteins could open new perspectives in the setting of specific immunotherapeutic strategies for the treatment of neurodegenerative diseases. Therefore, we have reviewed the pathogenic hypothesis in neurodegenerative pathologies, underling the links between the deposition of misfolded protein mechanisms and the immune activation. Related Articles | Metrics

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To treat or not to treat Alzheimer’s disease by the ketogenic diet? That is the question Marzena Ułamek-Kozioł, Ryszard Pluta 2020, 15 (5):  857-858.  doi: 10.4103/1673-5374.268900 Abstract ( 124 )   PDF (233KB) ( 172 )   Save AD is a serious neurological disorder worldwide that affects about 26 million people, and whose prevalence has been calculated to quadruple by 2050, thus reaching over 1% of the total population, with the highest prevalence occurring in both adults and elderly (Pluta et al., 2018). Neurodegenerative processes of the sporadic form of AD probably start 20 years before the clinical onset of the disorder (Pluta et al., 2018). This disease is the most important cause of dementia in world aged society (~75%). AD is a disorder that affects not only patients but also their caregivers. The social and economic burden associated with AD was calculated as an example in the United States alone; 600 billion dollars annually is spent on caring for AD patients (Pluta et al., 2018). AD is the one of the great health-care challenges of the 21st century. The incidence of AD, a chronic and progressive neurodegenerative disorder, is increasing, as well as the need for efficient methods of diagnosis, prevention and treatment (Pluta et al., 2018). The characteristic clinical and neuropathological hallmarks of AD are: dementia as the main clinical symptom and in post-mortem neuropathological examination, the presence of amyloid plaques as well as neurofibrillary tangles and loss of neurons in the brain of AD patients. The role of amyloid and tau protein is questioned in the etiology of AD and other causes such as ischemic etiology are being considered (Pluta and Ułamek-Kozioł, 2019). There are several treatments that are not causal but symptomatic that are not effective, especially for advanced disease. To date, only a few drugs are approved, such as acetylcholinesterase inhibitors and memantine. Drugs that regulate partly the activity of neurotransmitters and partly alleviate behavioral symptoms. Other treatment options include active and passive immunization, anti-aggregation specifics, and secretase inhibitors. The road to clarity AD etiology, early final ante mortem diagnosis and treatment has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Research has recently been launched to identify new mechanisms underlying AD that could be the target of new prevention strategies (Pluta and Ułamek-Kozioł, 2019). Therefore, other treatment options can be recommended, and the ketogenic diet seems to be an interesting last resort solution at the moment (Rusek et al., 2019). The diet contains large amounts of fat and low carbohydrates with vitamin supplementation. New scientific articles suggest that a low-carbohydrate and high-fat ketogenic diet may help alleviate the brain damage in AD (Ota et al., 2019; Rusek et al., 2019). A ketogenic diet can alleviate the effects of impaired glucose metabolism in AD by providing ketones as an additional source of energy. Here, based on new data, we have presented that a ketogenic diet can be effective in preventing and treating AD, but both ketone bodies production and carbohydrate reduction are needed to achieve this. Related Articles | Metrics

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Glycogen synthase kinase 3: a crucial regulator of axotomy-induced axon regeneration Jinlian Liu, Qing Zhou, Chaoqun Liu, Chunfeng Liu, Saijilafu 2020, 15 (5):  859-860.  doi: 10.4103/1673-5374.268899 Abstract ( 100 )   PDF (268KB) ( 193 )   Save Following nerve injury, axonal disconnection in neurons usually results in persistent functional deficits, such as paralysis. However, axons in the adult mammalian central nervous system (CNS) have very limited regenerative ability. Understanding the molecular mechanism of controlling axon regeneration can provide idea for the design of effective therapeutic interventions for CNS injury, such as spinal cord injuries. Efficient axonal regeneration is achieved via gene expression in the neuronal soma, axonal transport of raw materials along the shaft, and membrane and cytoskeleton assembly at the nerve growth cone. Each process is delicately regulated by spatial-temporal controlled signaling pathways that target distinct effectors. Gene expression in the neuronal soma, especially of transcription factors, is often activated immediately following nerve injury. Related Articles | Metrics

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Cerebrospinal fluid neurogranin as a new player in prion disease diagnosis and prognosis. Anna Villar-Piqué, Inga Zerr, Franc Llorens 2020, 15 (5):  861-862.  doi: 10.4103/1673-5374.268901 Abstract ( 103 )   PDF (711KB) ( 172 )   Save Ng is a calmodulin-binding protein mainly expressed in cerebral structures such as the cortex, hippocampus and striatum. It is mainly located in the dendritic processes, particularly in post-synaptic compartments, but also in the cytosolic compartment, being likely involved in the regulation of the intracellular calcium-calmodulin signaling pathway (Represa et al., 1990). In the last decade, a plethora of studies have demonstrated that cerebrospinal fluid (CSF) Ng is increased in AD patients and in individuals with an ADlike CSF profile (Kester et al., 2015a). This increase seems to be disease-specific because other neurodegenerative conditions including frontotemporal dementia, Lewy body dementia, Parkinson’s disease, progressive supranuclear palsy, multiple system atrophy or Huntington’s disease, present CSF Ng concentrations similar to controls (Wellington et al., 2016). Ng levels in CSF appear to be elevated in mild cognitive impairment (MCI)-affected individuals who progress to AD and are highly related to memory and cognitive function (Kester et al., 2015a; Tarawneh et al., 2016), which indicates that this protein may serve as an early AD biomarker with diagnostic utility in pre-dementia disease stages, and with prognostic utility to predict cognitive decline and MCI-to-AD conversion. Related Articles | Metrics

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Challenges in studying geographic atrophy (GA) age-related macular degeneration: the potential of a new mouse model with GA-like features J. Arjuna Ratnayaka, Andrew J. Lotery 2020, 15 (5):  863-864.  doi: 10.4103/1673-5374.268972 Abstract ( 120 )   PDF (746KB) ( 285 )   Save Loss of central vision critical to everyday activities such as reading, face-recognition and driving due to damage in the central retina (the macula) is the leading cause of irreversible blindness amongst adults in the developed world. This condition, termed age-related macular degeneration (AMD), is a complex, chronic degenerative disease driven by a combination of genetic and lifestyle risk factors. Early signs of retinal changes in people as young as 30–40 years have been reported, although these individuals appear to be asymptomatic. However, by the age of 65, the disease is present in ~3% of individuals, which increases dramatically to affect 1/3 of individuals by the eighth decade of life. Early to intermediate AMD is estimated to affect ~150 million individuals globally, with another 10 million individuals suffering from end-stage, sight-threatening forms. These terminal stages are broadly grouped into dry (geographic atrophy, GA) or wet (choroidal neovascular, CNV) AMD (Sarks et al., 1988; Bird et al., 2014), with similar frequencies reported in patients. Recent advances in identifying genetic risk factors, including our discoveries in this field, indicate an initial shared pathology before progressing to aforementioned late-stage phenotypes. Currently, GA patients have no effective treatment, which may in part be due to the lack of good in vivo models for GA studies. Here, we summarize our new findings that describe an altogether new mouse model with GA-like features which shows progressive outer retinal pathology (Ibbett et al., 2019) that can be used to gain novel insights into GA and potentially as a tool for drug development. Related Articles | Metrics

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RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C Li-Min Guo, Zhen Wang, Shi-Ping Li, Mi Wang, Wei-Tao Yan, Feng-Xia Liu, Chu-Dong Wang, Xu-Dong Zhang, Dan Chen, Jie Yan, Kun Xiong 2020, 15 (5):  865-874.  doi: 10.4103/1673-5374.268902 Abstract ( 143 )   PDF (10536KB) ( 26 )   Save Methamphetamine is one of the most prevalent drugs abused in the world. Methamphetamine abusers usually present with hyperpyrexia (39°C), hallucination and other psychiatric symptoms. However, the detailed mechanism underlying its neurotoxic action remains elusive. This study investigated the effects of methamphetamine + 39°C on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats. Primary cortex neurons were exposed to 1 mM methamphetamine + 39°C. Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39°C triggered obvious necrosis-like death in cultured primary cortical neurons, which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially. Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39°C for 3 hours. After pre-treatment with RIP3 inhibitor GSK’872, propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased; RIP3 and MLKL protein expression significantly decreased. Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse. Taken together, the above results suggest that methamphetamine + 39°C can induce RIP3/MLKL regulated necroptosis, thereby resulting in neurotoxicity. The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University, China (approval numbers: 2017-S026 and 2017-S033) on March 7, 2017. Related Articles | Metrics

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Brain activation induced by different strengths of hand grasp: a functional magnetic resonance imaging study Hyeok Gyu Kwon, Ju Sang Kim, Mi Young Lee 2020, 15 (5):  875-879.  doi: 10.4103/1673-5374.268907 Abstract ( 195 )   PDF (737KB) ( 291 )   Save Mirror neuron system can be activated by observation and execution of an action. It has an important function of action understanding. We investigated brain activations in humans by observing the strength of a hand grasp using functional magnetic resonance imaging. Twenty right-handed healthy individuals, consisting of 10 males and 10 females, aged 22.40 ± 2.04 years, were recruited into this study from September to November 2017 via posters. Light hand grasp task video showed a hand lightly grasping and releasing a ball repeatedly. Powerful hand grasp task video showed a hand tightly grasping and releasing a ball repeatedly. Functional magnetic resonance imaging block design paradigm comprised five stimulation blocks alternating with five baseline blocks. Stimulation blocks were presented with two stimulus tasks, consisting of a light grasp and a powerful grasp. Region of interest was defined around the inferior parietal lobule, inferior frontal gyrus, and superior temporal sulcus which have been called mirror neuron system. The inferior parietal lobule, fusiform, postcentral, occipital, temporal, and frontal gyri were activated during light and powerful grasp tasks. The BOLD signal response of a powerful grasp was stronger than that of a light grasp. These results suggest that brain activation of the inferior parietal lobule, which is the core brain region of the mirror neuron system, was stronger in the powerful grasp task than in the light grasp task. We believe that our results might be helpful for instructing rehabilitation of brain injury. This study was approved by the Institutional Review Board of Daegu Oriental Hospital of Daegu Haany University on September 8, 2017 (approval No. DHUMC-D-17020-PRO-01). Related Articles | Metrics

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Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability Dan Lyu, Ning Tang, Andrew W. Womack, Yong-Jin He, Qing Lin 2020, 15 (5):  880-886.  doi: 10.4103/1673-5374.268929 Abstract ( 132 )   PDF (1301KB) ( 202 )   Save Ketamine exposure can lead to selective neuroapoptosis in the developing brain. p66ShcA, the cellular adapter protein expressed selectively in immature neurons, is a known pro-apoptotic molecule that triggers neuroapoptosis when activated. Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg, six times at 2-hour intervals. At 0, 1, 3, and 6 hours after final injection, western blot assay was used to detect the expression of cleaved caspase-3, p66ShcA, and phosphorylated p66ShcA. We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours. The same procedure was performed on a different group of rats. At the age of 4 weeks, spatial learning and memory abilities were tested with the Morris water maze. Latency to find the hidden platform for these rats was longer than it was for control rats, although the residence time in the target quadrant was similar. These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period. This may have contributed to the deficit in spatial learning and memory that persisted into adulthood. The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington, USA (approval No. A13.008) on January 22, 2013. Related Articles | Metrics

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Korean red ginseng promotes hippocampal neurogenesis in mice Sun Ryu, Hyongjun Jeon, Hee-Young Kim, Sungtae Koo, Seungtae Kim 2020, 15 (5):  887-893.  doi: 10.4103/1673-5374.268905 Abstract ( 245 )   PDF (1964KB) ( 189 )   Save Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory. Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve learning and memory; however, the mechanisms are still elusive. Therefore, we evaluated whether KRG can promote cognitive function and enhance neurogenesis in the hippocampus. Eight-week-old male C57BL/6 mice received 50 mg/kg of 5-bromo-2′-deoxyuridine (BrdU) intraperitoneally and 100 mg/kg of KRG or vehicle orally once a day for 14 days. Pole, Rotarod and Morris water maze tests were performed and the brains were collected after the last behavioral test. Changes in the numbers of BrdU- and BrdU/ doublecortin (DCX; a marker for neuronal precursor cells and immature neurons)-positive cells in the dentate gyrus and the gene expression of proliferating cell nuclear antigen (a marker for cell differentiation), cerebral dopamine neurotrophic factor and ciliary neurotrophic factor in the hippocampus were then investigated. KRG-treated mice came down the pole significantly faster and stood on the rotarod longer than vehicle-treated mice. The Morris water maze test showed that KRG administration enhanced the learning and memory abilities significantly. KRG also significantly increased BrdU- and BrdU/DCX-positive cells in the dentate gyrus as well as the proliferating cell nuclear antigen, cerebral dopamine neurotrophic factor and ciliary neurotrophic factor mRNA expression levels in the hippocampus compared to vehicle. Administration of KRG promotes learning and memory abilities, possibly by enhancing hippocampal neurogenesis. This study was approved by the Pusan National University Institutional Animal Care and Use Committee (approval No. PNU-2016-1071) on January 19, 2016. Related Articles | Metrics

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Rosmarinic acid ameliorates hypoxia/ischemia induced cognitive deficits and promotes remyelination Man Li, Miao-Miao Cui, Nwobodo Alexander Kenechukwu, Yi-Wei Gu, Yu-Lin Chen, Si-Jing Zhong, Yu-Ting Gao, Xue-Yan Cao, Li Wang, Fu-Min Liu, Xiang-Ru Wen 2020, 15 (5):  894-902.  doi: 10.4103/1673-5374.268927 Abstract ( 195 )   PDF (4725KB) ( 202 )   Save Rosmarinic acid, a common ester extracted from Rosemary, Perilla frutescens, and Salvia miltiorrhiza Bunge, has been shown to have protective effects against various diseases. This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury. The right common carotid artery of 3-day-old rats was ligated for 2 hours. The rats were then prewarmed in a plastic container with holes in the lid, which was placed in 37°C water bath for 30 minutes. Afterwards, the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models. The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days. At 22 days after birth, rosmarinic acid was found to improve motor, anxiety, learning and spatial memory impairments induced by hypoxia/ischemia injury. Furthermore, rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone. After hypoxia/ischemia injury, rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure. Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2. These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum. This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University, China (approval No. 20161636721) on September 16, 2017. Related Articles | Metrics

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Selective brain hypothermia-induced neuroprotection against focal cerebral ischemia/reperfusion injury is associated with Fis1 inhibition Ya-Nan Tang, Gao-Feng Zhang, Huai-Long Chen, Xiao-Peng Sun, Wei-Wei Qin, Fei Shi, Li-Xin Sun, Xiao-Na Xu, Ming-Shan Wang 2020, 15 (5):  903-911.  doi: 10.4103/1673-5374.268973 Abstract ( 94 )   PDF (2733KB) ( 211 )   Save Selective brain hypothermia is considered an effective treatment for neuronal injury after stroke, and avoids the complications of general hypothermia. However, the mechanisms by which selective brain hypothermia affects mitochondrial fission remain unknown. In this study, we investigated the effect of selective brain hypothermia on the expression of fission 1 (Fis1) protein, a key factor in the mitochondrial fission system, during focal cerebral ischemia/reperfusion injury. Sprague-Dawley rats were divided into four groups. In the sham group, the carotid arteries were exposed only. In the other three groups, middle cerebral artery occlusion was performed using the intraluminal filament technique. After 2 hours of occlusion, the filament was slowly removed to allow blood reperfusion in the ischemia/reperfusion group. Saline, at 4°C and 37°C, were perfused through the carotid artery in the hypothermia and normothermia groups, respectively, followed by restoration of blood flow. Neurological function was assessed with the Zea Longa 5-point scoring method. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining, and apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Fis1 and cytosolic cytochrome c levels were assessed by western blot assay. Fis1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction. Mitochondrial ultrastructure was evaluated by transmission electron microscopy. Compared with the sham group, apoptosis, Fis1 protein and mRNA expression and cytosolic cytochrome c levels in the cortical ischemic penumbra and cerebral infarct volume were increased after reperfusion in the other three groups. These changes caused by cerebral ischemia/reperfusion were inhibited in the hypothermia group compared with the normothermia group. These findings show that selective brain hypothermia inhibits Fis1 expression and reduces apoptosis, thereby ameliorating focal cerebral ischemia/reperfusion injury in rats. Experiments were authorized by the Ethics Committee of Qingdao Municipal Hospital of China (approval No. 2019008). Related Articles | Metrics

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Expression and effect of sodium-potassium-chloride cotransporter on dorsal root ganglion neurons in a rat model of chronic constriction injury Chao-Yang Tan, Yan-Ping Wang, Yuan-Yuan Han, Bi-Han Lu, Wei Ji, Li-Cang Zhu, Yang Wang, Wen-Yan Shi, Li-Ya Shan, Liang Zhang, Ke-Tao Ma, Li Li, Jun-Qiang Si 2020, 15 (5):  912-921.  doi: 10.4103/1673-5374.268904 Abstract ( 102 )   PDF (2198KB) ( 235 )   Save Sodium-potassium-chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) are associated with the transmission of peripheral pain. We investigated whether the increase of NKCC1 and KCC2 is associated with peripheral pain transmission in dorsal root ganglion neurons. To this aim, rats with persistent hyperalgesia were randomly divided into four groups. Rats in the control group received no treatment, and the rat sciatic nerve was only exposed in the sham group. Rats in the chronic constriction injury group were established into chronic constriction injury models by ligating sciatic nerve and rats were given bumetanide, an inhibitor of NKCC1, based on chronic constriction injury modeling in the chronic constriction injury + bumetanide group. In the experiment measuring thermal withdrawal latency, bumetanide (15 mg/kg) was intravenously administered. In the patch clamp experiment, bumetanide (10 μg/μL) and acutely isolated dorsal root ganglion neurons (on day 14) were incubated for 1 hour, or bumetanide (5 μg/μL) was intrathecally injected. The Hargreaves test was conducted to detect changes in thermal hyperalgesia in rats. We found that the thermal withdrawal latency of rats was significantly decreased on days 7, 14, and 21 after model establishment. After intravenous injection of bumetanide, the reduction in thermal retraction latency caused by model establishment was significantly inhibited. Immunohistochemistry and western blot assay results revealed that the immune response and protein expression of NKCC1 in dorsal root ganglion neurons of the chronic constriction injury group increased significantly on days 7, 14, and 21 after model establishment. No immune response or protein expression of KCC2 was observed in dorsal root ganglion neurons before and after model establishment. The Cl– (chloride ion) fluorescent probe technique was used to evaluate the change of Cl– concentration in dorsal root ganglion neurons of chronic constriction injury model rats. We found that the relative optical density of N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (a Cl– fluorescent probe whose fluorescence Cenintensity decreases as Cl– concentration increases) in the dorsal root ganglion neurons of the chronic constriction injury group was significantly decreased on days 7 and 14 after model establishment. The whole-cell patch clamp technique revealed that the resting potential and action potential frequency of dorsal root ganglion neurons increased, and the threshold and rheobase of action potentials decreased in the chronic constriction injury group on day 14 after model establishment. After bumetanide administration, the above indicators were significantly suppressed. These results confirm that CCI can induce abnormal overexpression of NKCC1, thereby increasing the Cl– concentration in dorsal root ganglion neurons; this then enhances the excitability of dorsal root ganglion neurons and ultimately promotes hyperalgesia and allodynia. In addition, bumetanide can achieve analgesic effects. All experiments were approved by the Institutional Ethics Review Board at the First Affiliated Hospital, College of Medicine, Shihezi University, China on February 22, 2017 (approval No. A2017-169-01). Related Articles | Metrics

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Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction Dao-Xia Guo, Zheng-Bao Zhu, Chong-Ke Zhong, Xiao-Qing Bu, Li-Hua Chen, Tan Xu, Li-Bing Guo, Jin-Tao Zhang, Dong Li, Jian-Hui Zhang, Zhong Ju, Chung-Shiuan Chen, Jing Chen, Yong-Hong Zhang, Jiang He 2020, 15 (5):  922-928.  doi: 10.4103/1673-5374.268928 Abstract ( 138 )   PDF (429KB) ( 144 )   Save Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30–0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013. Related Articles | Metrics

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Effects of dexmedetomidine and dexketoprofen on the conduction block of rat sciatic nerve Sengal Bagci Taylan, Hulagu Bariskaner 2020, 15 (5):  929-935.  doi: 10.4103/1673-5374.268926 Abstract ( 94 )   PDF (1524KB) ( 218 )   Save Dexmedetomidine is a selective α2-adrenoceptor agonist that is used because of its sedative, anxiolytic, and analgesic effects. Dexketoprofen, which is used as an analgesic, is a nonselective nonsteroidal anti-inflammatory drug (NSAID). The use of dexmedetomidine and dexketoprofen as adjuvants to local anesthetics for the peripheral nerve is gradually increasing. In this study, we aimed to investigate the effects of different doses of dexmedetomidine and dexketoprofen on conduction block of rat sciatic nerve. The isolated sciatic nerve from adult rats was transferred to a nerve chamber. The compound action potentials (CAPs) were recorded from stimulated nerve with electrophysiological methods. Dexmedetomidine (n = 8) and dexketoprofen (n = 8) were administered in the chamber with cumulative concentrations of 10–9 to 10–5 M, and the CAPs were recorded for 5 and 10 minutes. The CAP parameters were calculated. Both dexmedetomidine and dexketoprofen significantly depressed all CAP parameters in a dose-dependent manner compared with the control group, i.e., the group in which rats did not receive treatment. CAP parameters showed there was no significant difference in nerve conduction inhibition between dexmedetomidine and dexketoprofen. Higher doses of dexmedetomidine suppressed the conduction in the fast-conducting fibers; however, dexketoprofen was found to suppress the conduction in the slow-conducting fibers in a time-dependent manner and suppress the conduction in the medium- and slow-conducting fibers in a dose-dependent manner. These findings suggest that dexmedetomidine and dexketoprofen exhibit better anesthetic effects on peripheral nerve through different ways of action. The experimental procedures were approved by the Necmettin Erbakan University on January 30, 2013 (approval No. 2013-024). Related Articles | Metrics

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Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus Dong-Qi Lin, Xin-Ying Cai, Chun-Hua Wang, Bin Yang, Ri-Sheng Liang 2020, 15 (5):  936-943.  doi: 10.4103/1673-5374.268903 Abstract ( 123 )   PDF (6021KB) ( 196 )   Save Hippocampal neurons undergo various forms of cell death after status epilepticus. Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors. However, there are no reports of necroptosis in mouse models of status epilepticus. Therefore, in this study, we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus, and, furthermore, we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis. A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid, 12 mg/kg. Different concentrations of necrostatin- 1 (10, 20, 40, and 80 μM) were administered into the lateral ventricle 15 minutes before kainic acid injection. Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins. Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy. The 40 μM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region. Furthermore, necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL, RIP1, and RIP3) and apoptosis-related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2. Taken together, our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus, with the 40 μM concentration of the compound having an optimal effect. The experiments were approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-032) on November 9, 2016. Related Articles | Metrics

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Osmotic pressure of serum and cerebrospinal fluid in patients with suspected neurological conditions Tetsuya Akaishi, Toshiyuki Takahashi, Ichiro Nakashima, Michiaki Abe, Masashi Aoki, Tadashi Ishii 2020, 15 (5):  944-947.  doi: 10.4103/1673-5374.268906 Abstract ( 156 )   PDF (320KB) ( 498 )   Save Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells. The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow. However, osmotic pressure- related factors have not been studied until now. In this prospective observational study, to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF), we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions. Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg. Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007, respectively, the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e., 290.5–291.5 mOsm/L). There was strong correlation between CSF osmolality and serum osmolality, but the difference in osmolality between serum and CSF was not correlated with serum osmolality, serum electrolyte levels, protein levels, or quotient of albumin. In conclusion, CSF osmolarity was suggested to be equal to serum osmolarity. Osmolarity is not one of the driving forces of this bulk flow. Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma. This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No. IRB No. 2015-1-257) on July 29, 2015. Related Articles | Metrics

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Dynamic expression of Slit1–3 and Robo1–2 in the mouse peripheral nervous system after injury Bing Chen, Lauren Carr, Xin-Peng Dun 2020, 15 (5):  948-958.  doi: 10.4103/1673-5374.268930 Abstract ( 189 )   PDF (18000KB) ( 48 )   Save The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors. Although we previously reported that Slit1–3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system, how this expression changes after injury has not been well studied. Herein, we constructed a peripheral nerve injury mouse model by transecting the right sciatic nerve. At 14 days after injury, quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1–3 and Robo1–2 in L4–5 spinal cord and dorsal root ganglia, as well as the sciatic nerve. Immunohistochemical analysis was performed to examine Slit1–3, Robo1–2, neurofilament heavy chain, F4/80, and vimentin in L4–5 spinal cord, L4 dorsal root ganglia, and the sciatic nerve. Co-expression of Slit1–3 and Robo1–2 in L4 dorsal root ganglia was detected by in situ hybridization. In addition, Slit1–3 and Robo1–2 protein expression in L4–5 spinal cord, L4 dorsal root ganglia, and sciatic nerve were detected by western blot assay. The results showed no significant changes of Slit1–3 or Robo1–2 mRNA expression in the spinal cord within 14 days after injury. In the dorsal root ganglion, Slit1–3 and Robo1–2 mRNA expression were initially downregulated within 4 days after injury; however, Robo1–2 mRNA expression returned to the control level, while Slit1–3 mRNA expression remained upregulated during regeneration from 4–14 days after injury. In the sciatic nerve, Slit1–3 and their receptors Robo1–2 were all expressed in the proximal nerve stump; however, Slit1, Slit2, and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury. Slit3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after injury. Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge. Robo1 was also upregulated in Schwann cells of the distal nerve stump within 14 days after injury. Our findings indicate that Slit3 is the major ligand expressed in the nerve bridge and distal nerve stump during peripheral nerve regeneration, and Slit3/Robo signaling could play a key role in peripheral nerve repair after injury. This study was approved by Plymouth University Animal Welfare Ethical Review Board (approval No. 30/3203) on April 12, 2014. Related Articles | Metrics

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Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury Ji-Peng Jiang, Xiao-Yin Liu, Fei Zhao, Xiang Zhu, Xiao-Yin Li, Xue-Gang Niu, Zi-Tong Yao, Chen Dai, Hui-You Xu, Ke Ma, Xu-Yi Chen, Sai Zhang 2020, 15 (5):  959-968.  doi: 10.4103/1673-5374.268974 Abstract ( 179 )   PDF (5400KB) ( 259 )   Save Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord. Indeed, cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration. This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord. This scaffold allows cell growth in vitro and in vivo. To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury. Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed), spinal cord injury (transection injury of T10 spinal cord without any transplantation), 3D-CF (3D scaffold was transplanted into the local injured cavity), and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity. Neuroelectrophysiology, imaging, hematoxylin-eosin staining, argentaffin staining, immunofluorescence staining, and western blot assay were performed. Apart from the sham group, neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups. Moreover, latency of the 3D-CF + NSCs group was significantly reduced, while the amplitude was significantly increased in motor evoked potential tests. The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group. Moreover, regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups. These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord. This study was approved by the Institutional Animal Care and Use Committee of People’s Armed Police Force Medical Center in 2017 (approval No. 2017-0007.2). Related Articles | Metrics