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    15 January 2017, Volume 12 Issue 1 Previous Issue    Next Issue
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    Celebration of the 10th Anniversary Neural Regeneration Research
    Kwok-fai So, Xiao-Ming Xu
    2017, 12 (1):  5-6.  doi: 10.4103/1673-5374.198963
    Abstract ( 127 )   PDF (1049KB) ( 451 )   Save
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    Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury
    Mary Wurzelmann, Jennifer Romeika, Dong Sun
    2017, 12 (1):  7-12.  doi: 10.4103/1673-5374.198964
    Abstract ( 304 )   PDF (345KB) ( 659 )   Save

    Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood brain-barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.   

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    Blood microRNAs as potential diagnostic markers for hemorrhagic stroke
    Bridget Martinez, Philip V. Peplow
    2017, 12 (1):  13-18.  doi: 10.4103/1673-5374.198965
    Abstract ( 200 )   PDF (359KB) ( 665 )   Save

    Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke, which in current practice is performed by computerized tomography (CT) or magnetic resonance imaging (MRI) scans. A panel of microRNAs could be an extremely useful clinical tool in distinguishing between hemorrhagic and ischemic stroke. This review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal models. It also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage stroke. The miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic stroke. Decreased or increased miRNA levels may be needed either as prevention or treatment of stroke. Administration in vivo of miR-130a inhibitor or miRNA mimic (miR-367, miR-223) in an intracerebral hemorrhage animal model improved neurological outcomes.

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    Emerging potential of exosomes for treatment of traumatic brain injury
    Ye Xiong, Asim Mahmood, Michael Chopp
    2017, 12 (1):  19-22.  doi: 10.4103/1673-5374.198966
    Abstract ( 282 )   PDF (302KB) ( 699 )   Save

    Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.

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    A new computational approach for modeling diffusion tractography in the brain
    Harsha T. Garimella, Reuben H. Kraft
    2017, 12 (1):  23-26.  doi: 10.4103/1673-5374.198967
    Abstract ( 230 )   PDF (383KB) ( 541 )   Save

    Computational models provide additional tools for studying the brain, however many techniques are currently disconnected from each other. There is a need for new computational approaches that span the range of physics operating in the brain. In this review paper, we offer some new perspectives on how the embedded element method can fill this gap and has the potential to connect a myriad of modeling genre. The embedded element method is a mesh superposition technique used within finite element analysis. This method allows for the incorporation of axonal fiber tracts to be explicitly represented. Here, we explore the use of the approach beyond its original goal of predicting axonal strain in brain injury. We explore the potential application of the embedded element method in areas of electrophysiology, neurodegeneration, neuropharmacology and mechanobiology. We conclude that this method has the potential to provide us with an integrated computational framework that can assist in developing improved diagnostic tools and regeneration technologies.

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    Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration
    Lindsey H. Forbes, Melissa R. Andrews
    2017, 12 (1):  27-30.  doi: 10.4103/1673-5374.198968
    Abstract ( 385 )   PDF (720KB) ( 352 )   Save

    Each neuronal subtype is distinct in how it develops, responds to environmental cues, and whether it is capable of mounting a regenerative response following injury. Although the adult central nervous system (CNS) does not regenerate, several experimental interventions have been trialled with successful albeit limited instances of axonal repair. We highlight here some of these approaches including extracellular matrix (ECM) modification, cellular grafting, gene therapy-induced replacement of proteins, as well as application of biomaterials. We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons. More specifically, we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts, whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons. Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration. We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.

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    Glial kon/NG2 gene network for central nervous system repair
    Maria Losada-Perez, Neale Harrison, Alicia Hidalgo
    2017, 12 (1):  31-34.  doi: 10.4103/1673-5374.198969
    Abstract ( 259 )   PDF (544KB) ( 622 )   Save

    The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response. A gene network involving Notch and prospero (pros) controls the balance between glial proliferation and differentiation in flies and mice, and promotes CNS repair at least in fruit-flies. A key missing link had been how to relate the function of NG2 to this gene network. Recent findings by Losada-Perez et al., published in JCB, demonstrated that the Drosophila NG2 homologue kon-tiki (kon) is functionally linked to Notch and pros in glia. By engaging in two feedback loops with Notch and Pros, in response to injury, Kon can regulate both glial cell number and glial shape homeostasis, essential for repair. Drosophila offers powerful genetics to unravel the control of stem and progenitor cells for regeneration and repair.

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    Endoplasmic reticulum-mitochondrial crosstalk: a novel role for the mitochondrial peptide humanin
    Parameswaran G. Sreekumar, David R. Hinton, Ram Kannan
    2017, 12 (1):  35-38.  doi: 10.4103/1673-5374.198970
    Abstract ( 333 )   PDF (437KB) ( 618 )   Save

    In this review, the interactive mechanisms of mitochondria with the endoplasmic reticulum (ER) are discussed with emphasis on the potential protective role of the mitochondria derived peptide humanin (HN) in ER stress. The ER and mitochondria are dynamic organelles capable of modifying their structure and function in response to changing environmental conditions. The ER and mitochondria join together at multiple sites and form mitochondria-ER associated membranes that participate in signal transduction pathways that are under active investigation. Our laboratory previously showed that HN protects cells from oxidative stress induced cell death and more recently, described the beneficial role of HN on ER stress-induced apoptosis in retinal pigment epithelium cells and the involvement of ER-mitochondrial cross-talk in cellular protection. The protection was achieved, in part, by the restoration of mitochondrial glutathione that was depleted by ER stress. Thus, HN may be a promising candidate for therapy for diseases that involve both oxidative and ER stress. Developing novel approaches for retinal delivery of HN, its analogues as well as small molecular weight ER stress inhibitors would prove to be a valuable approach in the treatment of age-related macular degeneration.

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    Kynurenine pathway metabolism and neuroinflammatory disease
    Nady Braidy, Ross Grant
    2017, 12 (1):  39-42.  doi: 10.4103/1673-5374.198971
    Abstract ( 564 )   PDF (481KB) ( 581 )   Save

    Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+ also serves as a substrate for the DNA ‘nick sensor’ and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.

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    The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models
    Syoichi Tashiro, Masaya Nakamura, Hideyuki Okano
    2017, 12 (1):  43-46.  doi: 10.4103/1673-5374.198972
    Abstract ( 273 )   PDF (447KB) ( 503 )   Save

    Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury (SCI). By contrast, there are still only a few studies have focused on the treatment of the chronically injured spinal cord, in which cell-based regenerative medicine seems less effective. Since the majority of SCI patients are in the chronic phase, representing a major challenge for the clinical application of cell-based regenerative medicine. Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized, there had been very few studies involving rehabilitative treatments to date. In a recent study, we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI, not only in additive but also in synergistic manner. Even though we have succeeded to outline
    the profiles of recovery secondary to the combination therapy, the mechanism underlying the effects remain unsolved. In this review article, we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.

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    Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair
    Mikel Sánchez, Ane Garate, Diego Delgado, Sabino Padilla
    2017, 12 (1):  47-52.  doi: 10.4103/1673-5374.198973
    Abstract ( 280 )   PDF (774KB) ( 729 )   Save

    Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet rich plasma (PRP) products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

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    Three-dimensional histology: new visual approaches to morphological changes during neural regeneration
    Hei Ming Lai, Ho Man Ng, Wutian Wu
    2017, 12 (1):  53-55.  doi: 10.4103/1673-5374.198974
    Abstract ( 277 )   PDF (569KB) ( 546 )   Save

    Three-dimensional (3D) histology utilizes tissue clearing techniques to turn intact tissues transparent, allowing rapid interrogation of tissue architecture in three dimensions. In this article, we summarized the available tissue clearing methods and classified them according to their physicochemical principles of operation,
    which provided a framework for one to choose the best techniques for various research settings. Recent attempts in addressing various questions regarding the degenerating and regenerating nervous system have been promising with the use of 3D histological techniques.

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    A revisit of rod microglia in preclinical studies
    Yanxia Rao, Yu-Xiang Liang, Bo Peng
    2017, 12 (1):  56-57.  doi: 10.4103/1673-5374.195276
    Abstract ( 155 )   PDF (379KB) ( 541 )   Save
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    Past, present and future of preserving and restoring function in the visual system: removing galectin-3 as a promising treatment
    Silmara de Lima, Henrique Rocha Mendonça, Camila Oliveira Goulart, Ana M. Blanco Martinez
    2017, 12 (1):  58-59.  doi: 10.4103/1673-5374.198975
    Abstract ( 229 )   PDF (254KB) ( 315 )   Save
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    Tauroursodeoxycholic acid: more than just a neuroprotective bile conjugate
    Lorenzo Romero-Ramírez, Manuel Nieto-Sampedro,Natalia Yanguas-Casás
    2017, 12 (1):  62-63.  doi: 10.4103/1673-5374.198979
    Abstract ( 616 )   PDF (554KB) ( 747 )   Save
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    Insights into the protective role of immunity in neurodegenerative disease
    Cristoforo Comi, Giacomo Tondo
    2017, 12 (1):  64-65.  doi: 10.4103/1673-5374.198980
    Abstract ( 252 )   PDF (274KB) ( 396 )   Save
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    Traumatic brain injury and palliative care: a retrospective analysis of 49 patients receiving palliative care during 2013–2016 in Turkey
    Kadriye Kahveci, Metin Dinçer, Cihan Doger, Ayse Karhan Yaricı
    2017, 12 (1):  77-83.  doi: 10.4103/1673-5374.198987
    Abstract ( 327 )   PDF (355KB) ( 595 )   Save

     

    Traumatic brain injury (TBI), which is seen more in young adults, affects both patients and their families. The need for palliative care in TBI and the limits of the care requirement are not clear. The aim of this study was to investigate the length of stay in the palliative care centre (PCC), Turkey, the status of patients at discharge, and the need for palliative care in patients with TBI. The medical records of 49 patients with TBI receiving palliative care in PCC during 2013-2016 were retrospectively collected, including age and gender of patients, the length of stay in PCC, the cause of TBI, diagnosis, Glasgow Coma Scale score, Glasgow Outcome Scale score, Karnofsky Performance Status score, mobilization status, form of nutrition (oral, percutaneous endoscopic gastrostomy), pressure ulcers, and discharge status. These patients were aged 45.4 ± 20.2 years. The median length of stay in the PCC was 34.0 days. These TBI patients had a Glasgow Coma Scale score ≤ 8, were not mobilized, received tracheostomy and percutaneous endoscopic gastrostomy nutrition, and had pressure ulcers. No difference was found between those who were discharged to their home or other places (rehabilitation centre, intensive care unit and death) in respect of mobilization, percutaneous endoscopic gastrostomy, tracheostomy and pressure ulcers. TBI patients who were followed up in PCC were determined to be relatively young patients (45.4 ± 20.2 years) with mobilization and nutrition problems and pressure ulcer formation. As TBI patients have complex health conditions that require palliative care from the time of admittance to intensive care unit, provision of palliative care services should be integrated with clinical applications.
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    Neural differentiation of choroid plexus epithelial cells: role of human traumatic cerebrospinal fluid
    Elham Hashemi, Yousef Sadeghi, Abbas Aliaghaei, Afsoun Seddighi, Abbas Piryaei, Mehdi Eskandarian Broujeni, Fatemeh Shaerzadeh, Abdollah Amini, Ramin Pouriran
    2017, 12 (1):  84-89.  doi: 10.4103/1673-5374.198989
    Abstract ( 287 )   PDF (704KB) ( 747 )   Save

     

    As the key producer of cerebrospinal fluid (CSF), the choroid plexus (CP) provides a unique protective system around the central nervous system. CSF components are not invariable and they can change based on the pathological conditions of the central nervous system. The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells. CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF. Alterations in mRNA expression of Nestin and microtubule-associated protein (MAP2), as the specific markers of neurogenesis, and astrocyte marker glial fibrillary acidic protein (GFAP) in cultured CP epithelial cells were evaluated using quantitative real-time PCR. The data revealed that treatment with CSF (non-traumatic and traumatic) led to increase in mRNA expression levels of MAP2 and GFAP. Moreover, expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF, while treatment with traumatic CSF significantly increased its mRNA level compared to the cells cultured only in DMEM/F12 as control group. In conclusion, CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.
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    Breviscapine reduces neuronal injury caused by traumatic brain injury insult: partly associated with suppression of interleukin-6 expression
    Ling Jiang, Yue Hu, Xiang He, Qiang Lv, Ting-hua Wang, Qing-jie Xia
    2017, 12 (1):  90-95.  doi: 10.4103/1673-5374.198990
    Abstract ( 340 )   PDF (1024KB) ( 443 )   Save

    Breviscapine, extracted from the herb Erigeron breviscapus is widely used for the treatment of cardiovascular diseases, cerebral infarct, and stroke, but its mechanism of action remains unclear. This study established a rat model of traumatic brain injury induced by controlled cortical impact, and injected 75 μg breviscapine via the right lateral ventricle. We found that breviscapine significantly improved neurobehavioral dysfunction at 6 and 9 days after injection. Meanwhile, interleukin-6 expression was markedly down-regulated following breviscapine treatment.Our results suggest that breviscapine is effective in promoting neurological behavior after traumatic brain injury and the underlying molecular mechanism may be associated with the suppression of IL-6.

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    Inhibition of cerebral ischemia/reperfusion injuryinduced apoptosis: nicotiflorin and JAK2/STAT3 pathway
    Guang-qiang Hu, Xi Du, Yong-jie Li, Xiao-qing Gao, Bi-qiong Chen, Lu Yu
    2017, 12 (1):  96-102.  doi: 10.4103/1673-5374.198992
    Abstract ( 301 )   PDF (1434KB) ( 836 )   Save

    Nicotiflorin is a flavonoid extracted from Carthamus tinctorius. Previous studies have shown its cerebral protective effect, but the mechanism is undefined. In this study, we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway. The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion. Nicotiflorin (10 mg/kg) was administered by tail vein injection. Neuronal apoptosis was examined by hematoxylin-eosin staining andterminal deoxynucleotidyl transferase dUTP nick end labeling assay. Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining. Additionally, p-JAK2, p-STAT3, Bcl-2, Bax, and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay. Our results show that nicotiflorin alters the shape and structure of injured neurons, decreases the number of apoptotic neurons, down-regulates expression of p-JAK2, p-STAT3, caspase-3, and Bax, decreases the immune response of Bax, and up-regulates expression of Bcl-2 protein and the immune response. These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.

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    Computed tomography perfusion and computed tomography angiography for prediction of clinical outcomes in ischemic stroke patients after thrombolysis
    Jia-wei Pan, Xiang-rong Yu, Shu-yi Zhou, Jian-hong Wang, Jun Zhang, Dao-ying Geng, Tian-yu Zhang, Xin Cheng, Yi-feng Ling, Qiang Dong
    2017, 12 (1):  103-108.  doi: 10.4103/1673-5374.198994
    Abstract ( 287 )   PDF (521KB) ( 638 )   Save

     

    Cerebral blood perfusion and cerebrovascular lesions are important factors that can affect the therapeutic efficacy of thrombolysis. At present, the majority of studies focus on assessing the accuracy of lesion location using imaging methods before treatment, with less attention to predictions of outcomes after thrombolysis. Thus, in the present study we assessed the efficacy of combined computed tomography (CT) perfusion and CT angiography in predicting clinical outcomes after thrombolysis in ischemic stroke patients. The study included 52 patients who received both CT perfusion and CT angiography. Patients were divided into the following groups to compare clinical outcomes: (1) thrombolyzed and non-thrombolyzed patients, (2) thrombolytic patients with CT angiography showing the presence or absence of a vascular stenosis, (3) thrombolytic patients with CT perfusion showing the presence or absence of hemodynamic mismatch, and (4) according to different CT angiography and CT perfusion results. Short-term outcome was assessed by the 24-hour National Institution of Health Stroke Scale score change. Long-term outcome was assessed by the 3-month modified Rankin Scale score. Of 52 ischemic stroke patients, 29 were treated with thrombolysis and exhibited improved short-term outcomes compared with those without thrombolysis treatment (23 patients). Patients with both vascular stenosis and blood flow mismatch (13 patients) exhibited the best short-term outcome, while there was no correlation of long-term outcome with CT angiography or CT perfusion findings. These data suggest that combined CT perfusion and CT angiography are useful for predicting short-term outcome, but not long-term outcome, after thrombolysis.
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    Evidence of cortical reorganization of language networks after stroke with subacute Broca’s aphasia: a blood oxygenation level dependent-functional magnetic resonance imaging study
    Wei-hong Qiu, Hui-xiang Wu, Qing-lu Yang, Zhuang Kang, Zhao-cong Chen, Kui Li, Guo-rong Qiu, Chun-qing Xie, Gui-fang Wan, Shao-qiong Chen
    2017, 12 (1):  109-117.  doi: 10.4103/1673-5374.198996
    Abstract ( 277 )   PDF (654KB) ( 446 )   Save

     

    Aphasia is an acquired language disorder that is a common consequence of stroke. The pathogenesis of the disease is not fully understood, and as a result, current treatment options are not satisfactory. Here, we used blood oxygenation level-dependent functional magnetic resonance imaging to evaluate the activation of bilateral cortices in patients with Broca’s aphasia 1 to 3 months after stroke. Our results showed that language expression was associated with multiple brain regions in which the right hemisphere participated in the generation of language. The activation areas in the left hemisphere of aphasia patients were significantly smaller compared with those in healthy adults. The activation frequency, volumes, and intensity in the regions related to language, such as the left inferior frontal gyrus (Broca’s area), the left superior temporal gyrus, and the right inferior frontal gyrus (the mirror region of Broca’s area), were lower in patients compared with healthy adults. In contrast, activation in the right superior temporal gyrus, the bilateral superior parietal lobule, and the left inferior temporal gyrus was stronger in patients compared with healthy controls. These results suggest that the right inferior frontal gyrus plays a role in the recovery of language function in the subacute stage of stroke-related aphasia by increasing the engagement of related brain areas.
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    Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells
    Zhu-ran Zhao1 Wei-dong Yu, Cheng Shi, Rong Liang, Xi Chen, Xiao Feng, Xue Zhang, Qing Mu, Huan Shen, Jing-zhu Guo
    2017, 12 (1):  118-124.  doi: 10.4103/1673-5374.198997
    Abstract ( 258 )   PDF (1896KB) ( 449 )   Save

    Overexpression of receptor-interacting protein 140 (RIP140) promotes neuronal differentiation of N2a cells via extracellular regulated kinase 1/2 (ERK1/2) signaling. However, involvement of RIP140 in human neural differentiation remains unclear. We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells. Moreover, RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation, and positively correlated with the neural stem cell marker Nestin during later stages. Thus, ERK1/2 signaling may provide the underlying molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced.

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    Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury
    Li-jie Xie, Jin-xiu Huang, Jian Yang, Fen Yuan, Shuang-shuang Zhang, Qi-jing Yu, Ji Hu
    2017, 12 (1):  125-132.  doi: 10.4103/1673-5374.199004
    Abstract ( 264 )   PDF (996KB) ( 286 )   Save

     

    Propofol has been shown to exert neuroprotective effects on the injured spinal cord. However, the effect of propofol on the blood–spinal cord barrier (BSCB) after ischemia/reperfusion injury (IRI) is poorly understood. Therefore, we investigated whether propofol could maintain the integrity of the BSCB. Spinal cord ischemia/reperfusion injury (SCIRI) was induced in rabbits by infrarenal aortic occlusion for 30 minutes.Propofol, 30 mg/kg, was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion. Then, 48 hours later, we performed histological and mRNA/protein analyses of the spinal cord. Propofol decreased histological damage to the spinal cord, attenuated the reduction in BSCB permeability, downregulated the mRNA and protein expression levels of matrix metalloprotease-9 (MMP-9) and nuclear factor-κB (NF-κB), and upregulated the protein expression levels of occludin and claudin-5. Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression, by inhibiting the NF-κB signaling pathway, and by maintaining expression of tight junction proteins.
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    Real-time and wearable functional electrical stimulation system for volitional hand motor function control using the electromyography bridge method
    Hai-peng Wang, Zheng-yang Bi, Yang Zhou, Yu-xuan Zhou, Zhi-gong Wang, Xiao-ying Lv
    2017, 12 (1):  133-142.  doi: 10.4103/1673-5374.197139
    Abstract ( 345 )   PDF (1843KB) ( 661 )   Save

    Voluntary participation of hemiplegic patients is crucial for functional electrical stimulation therapy. A wearable functional electrical stimulation system has been proposed for real-time volitional hand motor function control using the electromyography bridge method. Through a series of novel design concepts, including the integration of a detecting circuit and an analog-to-digital converter, a miniaturized functional electrical stimulation circuit technique, a low-power super-regeneration chip for wireless receiving, and two wearable armbands, a prototype system has been established with reduced size, power, and overall cost. Based on wrist joint torque reproduction and classification experiments performed on six healthy subjects, the optimized surface electromyography thresholds and trained logistic regression classifier parameters were statistically chosen to establish wrist and hand motion control with high accuracy. Test results showed that wrist flexion/extension, hand grasp, and finger extension could be reproduced with high accuracy and low latency. This system can build a bridge of information transmission between healthy limbs and paralyzed limbs, effectively improve voluntary participation of hemiplegic patients, and elevate efficiency of rehabilitation training.

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    Transfer of the extensor indicis proprius branch ofposterior interosseous nerve to reconstruct ulnar nerve and median nerve injured proximally: an anatomical study
    Pei-ji Wang, Yong Zhang, Jia-ju Zhao, Ju-pu Zhou, Zhi-cheng Zuo, Bing-bing Wu
    2017, 12 (1):  143-148.  doi: 10.4103/1673-5374.199007
    Abstract ( 318 )   PDF (1047KB) ( 660 )   Save

     

    Proximal or middle lesions of the ulnar or median nerves are responsible for extensive loss of hand motor function. This occurs even when the most meticulous microsurgical techniques or nerve grafts are used. Previous studies had proposed that nerve transfer was more effective than nerve grafting for nerve repair. Our hypothesis is that transfer of the posterior interosseous nerve, which contains mainly motor fibers, to the ulnar or median nerve can innervate the intrinsic muscles of hands. The present study sought to investigate the feasibility of reconstruction of the deep branch of the ulnar nerve and the thenar branch of median nerve by transferring the extensor indicis proprius branch of the posterior interosseous nerve obtained from adult cadavers. The results suggested that the extensor indicis proprius branch of the posterior interosseous nerve had approximately similar diameters and number of fascicles and myelinated nerve fibers to those of the deep branch of ulnar nerve and the thenar branch of the median nerve. These confirm the feasibility of extensor indicis proprius branch of posterior interosseous nerve transfer for reconstruction of the deep branch of the ulnar nerve and the thenar branch of median nerve. This procedure could be a novel and effective method for the functional recovery of the intrinsic muscles of hands after ulnar nerve or median nerve injury.
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    Immunohistochemical evidence of axonal regrowth across polyethylene glycol-fused cervical cords in mice
    C-Yoon Kim, Hanseul Oh, Xiaoping Ren, Sergio Canavero
    2017, 12 (1):  149-150.  doi: 10.4103/1673-5374.199014
    Abstract ( 216 )   PDF (401KB) ( 351 )   Save
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    Molecular chaperones and hypoxic-ischemic encephalopathy
    Cong Hua, Wei-na Ju, Hang Jin, Xin Sun, Gang Zhao
    2017, 12 (1):  153-160.  doi: 10.4103/1673-5374.199008
    Abstract ( 242 )   PDF (450KB) ( 642 )   Save

    Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we provide an overview of the mechanisms of HIE and discuss the various treatment strategies. Given their critical role in the disease, molecular chaperones are promising therapeutic targets for HIE.

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    Multi-site spinal stimulation strategies to enhance locomotion afer paralysis
    Prithvi K. Shah, Yury Gerasimenko
    2017, 12 (1):  161-162.  doi: 10.4103/1673-5374.199010
    Abstract ( 117 )   PDF (496KB) ( 393 )   Save
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