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    15 April 2014, Volume 9 Issue 7 Previous Issue    Next Issue
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    Acrolein as a novel therapeutic target for motor and sensory deficits in spinal cord injury
    Jonghyuck Park, Breanne Muratori, Riyi Shi
    2014, 9 (7):  677-683.  doi: 10.4103/1673-5374.131564
    Abstract ( 233 )   PDF (305KB) ( 1003 )   Save

    In the hours to weeks following traumatic spinal cord injuries (SCI), biochemical processes are initiated that further damage the tissue within and surrounding the initial injury site: a process
    termed secondary injury. Acrolein, a highly reactive unsaturated aldehyde, has been shown to play a major role in the secondary injury by contributing significantly to both motor and sensory deficits. In particular, efforts have been made to elucidate the mechanisms of acrolein-mediated damage at the cellular level and the resulting paralysis and neuropathic pain. In this review, we will highlight the recent developments in the understanding of the mechanisms of acrolein in motor and sensory dysfunction in animal models of SCI. We will also discuss the therapeutic benefits of using acrolein scavengers to attenuate acrolein-mediated neuronal damage following SCI.

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    A brief review of recent advances in stem cell biology
    Jinhui Chen, Libing Zhou, Su-yue Pan
    2014, 9 (7):  684-687.  doi: 10.4103/1673-5374.131565
    Abstract ( 198 )   PDF (1728KB) ( 889 )   Save

    Stem cells have the remarkable potential to develop into many different cell types, essentially without limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer’s disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two  kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells. Recent breakthrough make it possible to convert or “reprogram” specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly discuss the recent progresses in this area.

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    The potential of endogenous neurogenesis for brain repair and regeneration following traumatic brain injury
    Dong Sun
    2014, 9 (7):  688-692.  doi: 10.4103/1673-5374.131567
    Abstract ( 287 )   PDF (730KB) ( 953 )   Save

    Traumatic brain injury (TBI) is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individuals each year. It had been thought that recovery from such injuries is severely limited due to the inability of the adult brain to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system (CNS) has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been observed in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.

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    Imaging brain plasticity after trauma
    Zhifeng Kou, Armin Iraji
    2014, 9 (7):  693-700.  doi: 10.4103/1673-5374.131568
    Abstract ( 309 )   PDF (945KB) ( 902 )   Save

    The brain is highly plastic after stroke or epilepsy; however, there is a paucity of brain plasticity investigation after traumatic brain injury (TBI). This mini review summarizes the most recent evidence of brain plasticity in human TBI patients from the perspective of advanced magnetic resonance imaging. Similar to other forms of acquired brain injury, TBI patients also demonstrated both structural reorganization as well as functional compensation by the recruitment of other    brain regions. However, the large scale brain network alterations after TBI are still unknown, and the field is still short of proper means on how to guide the choice of TBI rehabilitation or treatment plan to promote brain plasticity. The authors also point out the new direction of brain plasticity investigation.

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    Neuronal cell death and regeneration in diseases associated with advanced glycation end-products accumulation
    Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    2014, 9 (7):  701-702.  doi: 10.4103/1673-5374.131569
    Abstract ( 273 )   PDF (256KB) ( 783 )   Save

    Growing evidence indicates that neuronal abnormalities including neuronal cell death are associated with the pathogenesis of early diabetic retinopathy. Our previous study of human retinas indicate that mitochondrial and caspase-dependent cell death pathways are associated with retinal neuronal cell degeneration in patients with diabetes Prof. Toshiyuki Oshitari from Chiba University Graduate School of Medicine in Japan had studied and showed a survival effect on damaged retinal neurons induced by diabetic stress. They also found that NT-4 had the best neuroprotective and regenerative effect under high glucose conditions. Earlier study indicated that the maximum rescue ratio of caspase-1, -3, -8, and -9 inhibitors in cultured retinas was 60% in damaged retinal ganglion cells (RGCs). Thus, at least 40% of neuronal cell death in damaged RGCs in cultured retinas should be related to caspase-independent cell death mechanisms. However, no reports have focused on caspase-independent cell death pathways under diabetic stress including AGEs exposure.

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    Recent advances in the treatment of post-stroke aphasia
    Anna Zumbansen, Alexander Thiel
    2014, 9 (7):  703-706.  doi: 10.4103/1673-5374.131570
    Abstract ( 288 )   PDF (198KB) ( 1563 )   Save

    Speech and language therapy is the best treatment to improve language and functional communication in post-stroke aphasia. However, even well studied impairment-based approaches show limited effects on language recovery. Prof. Alexander Thiel from McGill University in Canada points out pharmacological (in particular Piracetam) and NIBS strategies (mainly inhibitory rTMS over the contralesional hemisphere) offer promising new ways to optimize SLT effects and clearly merit further research.

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    Role of nuclear factor kappa B in central nervous system regeneration
    Christian Engelmann, Falk Weih, Ronny Haenold
    2014, 9 (7):  707-711.  doi: 10.4103/1673-5374.131572
    Abstract ( 203 )   PDF (601KB) ( 1195 )   Save

    Activation of nuclear factor kappa B (NF-κB) is a hallmark of various central nervous system (CNS) pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-κB in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a transdominant negative mutant of its upstream regulator IκBα, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular program in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

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    Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations
    Aysegul Gunduz, Hatice Kumru, Alvaro Pascual-Leone
    2014, 9 (7):  712-718.  doi: 10.4103/1673-5374.131574
    Abstract ( 217 )   PDF (271KB) ( 1403 )   Save

    Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral  palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving the spasticity post-stroke, more prospective cohort studies involving large sample sizes are needed.

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    3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia
    Wanhong Zhao, Chao Luo, Jue Wang, Jian Gong, Bin Li, Yingxia Gong, Jun Wang, Hanqin Wang
    2014, 9 (7):  719-726.  doi: 10.4103/1673-5374.131576
    Abstract ( 251 )   PDF (649KB) ( 1448 )   Save

    3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study ligated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphthalide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby improving cerebral neuronal injury and cognitive deficits.

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    Neuronal apoptosis in cerebral ischemia/reperfusion area following electrical stimulation of fastigial nucleus
    Jingli Liu, Jinpin Li, Yi Yang, Xiaoling Wang, Zhaoxia Zhang, Lei Zhang
    2014, 9 (7):  727-734.  doi: 10.4103/1673-5374.131577
    Abstract ( 201 )   PDF (599KB) ( 1066 )   Save

    Previous studies have indicated that electrical stimulation of the cerebellar fastigial nucleus in rats may reduce brain infarct size, increase the expression of Ku70 in cerebral ischemia/reperfusion area, and decrease the number of apoptotic neurons. However, the anti-apoptotic mechanism of Ku70 remains unclear. In this study, fastigial nucleus stimulation was given to rats 24, 48, and 72 hours before cerebral ischemia/reperfusion injury. Results from the electrical stimulation group revealed that rats exhibited a reduction in brain infarct size, a significant increase in the expression of Ku70 in cerebral ischemia/reperfusion regions, and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Double immunofluorescence staining revealed no co-localization of Ku70 with TUNEL-positive cells. However, Ku70 partly co-localized with Bax protein in the cytoplasm of rats with cerebral ischemia/reperfusion injury. These findings suggest an involvement of Ku70 with Bax in the cytoplasm of rats exposed to electrical stimulation of the cerebellar fastigial nucleus, and may thus provide an understanding into the anti-apoptotic activity of Ku70 in cerebral ischemia/reperfusion injury.

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    Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells: possible involvement of stress proteins and gene expression
    Riadh Nciri, Ezzeddine Bourogaa, Samira Jbahi, Mohamed Salah Allagui, Abdelfattah Elfeki, Christian Vincent, Françoise Croute
    2014, 9 (7):  735-740.  doi: 10.4103/1673-5374.131578
    Abstract ( 223 )   PDF (244KB) ( 810 )   Save

    To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate (Li2CO2) for 25–50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 (CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II (CK2), threonine/tyrosine phosphatase 7 (PYST2), and dopamine beta-hydroxylase (DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above.

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    Houshiheisan compound prescription protects neurovascular units after cerebral ischemia
    Haizheng Wang, Lei Wang, Nan Zhang, Qi Zhang, Hui Zhao, Qiuxia Zhang
    2014, 9 (7):  741-748.  doi: 10.4103/1673-5374.131580
    Abstract ( 268 )   PDF (3981KB) ( 664 )   Save

    Houshiheisan is composed of wind-dispelling (chrysanthemun flower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root) and deficiency-nourishing (ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber) drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immunofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regulated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-β 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-β 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance deposition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra.

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    Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia
    Yaning Zhao, Jianmin Li, Qiqun Tang, Pan Zhang, Liwei Jing, Changxiang Chen, Shuxing Li
    2014, 9 (7):  749-756.  doi: 10.4103/1673-5374.131581
    Abstract ( 171 )   PDF (3675KB) ( 594 )   Save

    Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

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    Middle cerebral artery occlusion methods in rat versus mouse models of transient focal cerebral ischemic stroke
    Seunghoon Lee, Minkyung Lee, Yunkyung Hong, Jinyoung Won, Youngjeon Lee, Sung-Goo Kang, Kyu-Tae Chang, Yonggeun Hong
    2014, 9 (7):  757-758.  doi: 10.4103/1673-5374.131582
    Abstract ( 271 )   PDF (629KB) ( 1511 )   Save
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    Neuromelanin-sensitive magnetic resonance imaging: a promising technique for depicting tissue characteristics containing neuromelanin
    Ken Nakamura, Keizo Sugaya
    2014, 9 (7):  759-760.  doi: 10.4103/1673-5374.131583
    Abstract ( 341 )   PDF (456KB) ( 1138 )   Save

    Although the biological function of neuromelanin has not yet been determined, the selective vulnerability of neuromelanin-containing neurons in patients with Idiopathic Parkinson’s disease (IPD) suggests a role for this pigment in neurodegeneration. Dr. Keizo Sugaya from Tokyo Metropolitan Neurological Hospital in Japan shows that recently developed ultra-high-field magnetic resonance imaging (MRI) systems produce T1-weighted neuromelanin-sensitive images with very high spatial resolution, enabling the depiction of tissue containing neuromelanin. Here we review recent advances in neuromelanin-sensitive MRI in IPD and related conditions suggesting that neuromelanin may be a potential diagnostic biomarker for IPD.

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    The metabolic brain network in patients with Parkinson’s disease based on 18F-FDG PET imaging: evaluation of neuronal injury and regeneration
    Jingjie Ge, Ping Wu, Chuantao Zuo
    2014, 9 (7):  763-765.  doi: 10.4103/1673-5374.131586
    Abstract ( 237 )   PDF (570KB) ( 801 )   Save

    Over the past two decades, the development of functional imaging methods has greatly promoted our understanding on the changes of neurons following neurodegenerative disorders. Prof. Chuantao Zuo from Fudan University in China proposed that the application of a spatial covariance analysis on 18F-FDG PET imaging has led to the identification of a distinctive disease-related metabolic pattern. This pattern has proven to be useful in clinical diagnosis, disease progression monitoring as well as assessment of the neuronal changes before and after clinical treatment. It may potentially serve as an objective biomarker on disease progression monitoring , assessment , histological and functional evaluation of for related diseases.

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    Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment: a voxel-based lesion symptom mapping study
    Alexandria M. Reynolds, Denise M. Peters, Jennifer M. C. Vendemia, Lenwood P. Smith, Raymond C. Sweet, Gordon C. Baylis,Debra Krotish, Stacy L. Fritz
    2014, 9 (7):  766-772.  doi: 10.4103/1673-5374.131589
    Abstract ( 222 )   PDF (667KB) ( 2357 )   Save

    Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuronal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex. 

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    Early filiform needle acupuncture for poststroke depression: a meta-analysis of 17 randomized controlled clinical trials
    Jiping Zhang, Jing Chen, Junqi Chen, Xiaohui Li, Xueyan Lai, Shaoqun Zhang, Shengxu Wang
    2014, 9 (7):  773-784.  doi: 10.4103/1673-5374.131590
    Abstract ( 189 )   PDF (387KB) ( 1441 )   Save

    OBJECTIVE: To evaluate the effectiveness and safety of filiform needle acupuncture for poststroke depression, and to compare acupuncture with the therapeutic efficacy of antidepressant drugs.
    DATA RETRIEVAL: We retrieved data from the Chinese National Knowledge Infrastructure (1979–2012), Wanfang (1980–2012), VIP (1989–2012), Chinese Biomedical Literature (1975–2012), PubMed (1966–2012), Ovid Lww (–2012), and Cochrane Library (–2012) Database using the internet.
    SELECTION CRITERIA: Randomized controlled trials on filiform needle acupuncture versus antidepressant drugs for treatment of poststroke depression were included. Moreover, the included articles scored at least 4 points on the Jadad scale. Exclusion criteria: other acupuncture therapies as treatment group, not stroke-induced depression patients, score < 4 points, non-randomized controlled trials, or animal trials.
    MAIN OUTCOME MEASURES: These were the Hamilton Depression Scale scores, clinical effective rate, Self-Rating Depression Scale scores, Side Effect Rating Scale scores, and incidence of adverse reaction and events.
    RESULTS: A total of 17 randomized controlled clinical trials were included. Meta-analysis results displayed that after 4 weeks of treatment, clinical effective rate was better in patients treated with filiform needle acupuncture than those treated with simple antidepressant drugs [relative risk  = 1.11, 95% confidence interval (CI): 1.03–1.21, P = 0.01]. At 6 weeks, clinical effective rate was similar between filiform needle acupuncture and antidepressant drug groups. At 2 weeks after filiform needle acupuncture, Hamilton Depression Scale (17 items) scores were lower than in the antidepressant drug group (mean difference = −2.34, 95%CI: −3.46 to −1.22, P < 0.000,1). At 4 weeks, Hamilton Depression Scale (24 items) scores were similar between filiform needle acupuncture and antidepressant drug groups. Self-Rating Depression Scale scores were lower in filiform needle acupuncture group than in the antidepressant drug group. Side Effect Rating Scale was used in only two articles, and no meta-analysis was conducted. Safety evaluation of the 17 articles showed that gastrointestinal tract reactions such as nausea and vomiting were very common in the antidepressant drug group. Incidence of adverse reaction and events was very low in the filiform needle acupuncture group.
    CONCLUSION: Early filiform needle acupuncture for poststroke depression can perfectly control depression. Filiform needle acupuncture is safe and reliable. Therapeutic effects of filiform needle acupuncture were better than those of antidepressant drugs.

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