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    15 February 2017, Volume 12 Issue 2 Previous Issue    Next Issue
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    The promise of stem cell-based therapeutics in ophthalmology
    Israel Aharony, Shalom Michowiz, Nitza Goldenberg-Cohen
    2017, 12 (2):  173-180.  doi: 10.4103/1673-5374.200793
    Abstract ( 264 )   PDF (273KB) ( 665 )   Save

    The promising role of cellular therapies in the preservation and restoration of visual function has prompted intensive efforts to characterize embryonic, adult, and induced pluripotent stem cells for regenerative purposes. Three main approaches to the use of stem cells have been described: sustained drug delivery, immunomodulation, and differentiation into various ocular structures. Studies of the differentiation capacity of all three types of stem cells into epithelial, neural, glial and vascular phenotypes have reached proof-of-concept in culture, but the correction of vision is still in the early developmental stages, and the requirements for effective in vivo implementation are still unclear. We present an overview of some of the preclinical findings on stem-cell rescue and regeneration of the cornea and retina in acute injury and degenerative disorders.

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    Current view and perspectives in amyotrophic lateral sclerosis
    Stéphane Mathis, Philippe Couratier, Adrien Julian, Philippe Corcia, Gwendal Le Masson
    2017, 12 (2):  181-184.  doi: 10.4103/1673-5374.200794
    Abstract ( 158 )   PDF (340KB) ( 659 )   Save

    Amyotrophic lateral sclerosis (ALS), identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease). Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients. Nevertheless, the scientific knowledge in the field of ALS motor neuron degeneration is growing, with the prospect of new treatments. Based on this physiopathological knowledge, several new therapeutic targets are being studied, involving various mechanisms such as excitotoxicity, neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism and other attractive concepts. Moreover, it is also important to identify reliable biomarkers that will be essential components for future therapeutic development and study design in ALS. In this review, we present the main recent advances and promising therapeutics and biomarkers in the field of ALS.

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    Axonal remodeling in the corticospinal tract after stroke: how does rehabilitative training modulate it?
    Naohiko Okabe, Kazuhiko Narita, Osamu Miyamoto
    2017, 12 (2):  185-192.  doi: 10.4103/1673-5374.200792
    Abstract ( 286 )   PDF (883KB) ( 777 )   Save

    Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.

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    Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage
    Takeshi Okada, Hidenori Suzuk
    2017, 12 (2):  193-196.  doi: 10.4103/1673-5374.200795
    Abstract ( 307 )   PDF (506KB) ( 734 )   Save

    Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor (NF)-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.

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    The exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches
    Vivek Agrahari
    2017, 12 (2):  197-200.  doi: 10.4103/1673-5374.200796
    Abstract ( 271 )   PDF (619KB) ( 790 )   Save

    Delivering therapeutics to the central nervous system (CNS) and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier (BBB). The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant advantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed.

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    Intracellular compartmentation of cAMP promotes neuroprotection and regeneration of CNS neurons
    Evan G. Cameron, Michael S. Kapiloff
    2017, 12 (2):  201-202.  doi: 10.4103/1673-5374.200797
    Abstract ( 365 )   PDF (299KB) ( 505 )   Save
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    Astrogenesis versus astrogliosis
    Andrew O. Koob
    2017, 12 (2):  203-204.  doi: 10.4103/1673-5374.200798
    Abstract ( 386 )   PDF (227KB) ( 672 )   Save
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    Curcumin-primed and curcuminloaded exosomes: potential neural therapy
    Anuradha Kalani, Pankaj Chaturvedi, Osamu Miyamoto
    2017, 12 (2):  205-206.  doi: 10.4103/1673-5374.200799
    Abstract ( 257 )   PDF (477KB) ( 602 )   Save
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    Neuroprotective properties of dietary saffron: more than just a chemical scavenger?
    Nicholas V Skladnev, Daniel M Johnstone
    2017, 12 (2):  210-211.  doi: 10.4103/1673-5374.198976
    Abstract ( 304 )   PDF (140KB) ( 514 )   Save
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    Targeting the guanine-based purinergic system in Alzheimer’s disease
    Débora Lanznaster, Carla I. Tasca
    2017, 12 (2):  212-213.  doi: 10.4103/1673-5374.200801
    Abstract ( 279 )   PDF (483KB) ( 434 )   Save
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    Mitochondria in the context of Parkinson’s disease
    Patricia Villacé, Rosa M. Mella, Danel Kortazar
    2017, 12 (2):  214-215.  doi: 10.4103/1673-5374.200802
    Abstract ( 166 )   PDF (345KB) ( 637 )   Save
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    Neonatal seizures and disruption to neurotransmitter systems
    Stephanie M. Miller, Kate Goasdoue, S. Tracey Björkman
    2017, 12 (2):  216-217.  doi: 10.4103/1673-5374.200803
    Abstract ( 207 )   PDF (308KB) ( 446 )   Save
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    PDE5 inhibitors promote recovery of peripheral neuropathy in diabetic mice
    Lei Wang, Michael Chopp, Zheng Gang Zhang
    2017, 12 (2):  218-219.  doi: 10.4103/1673-5374.200804
    Abstract ( 321 )   PDF (143KB) ( 539 )   Save
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    Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes
    Bai Hui Chen, Joon Ha Park, JiHyeon Ahn, JeongHwi Cho, In Hye Kim, Jae Chul Lee, Moo-Ho Won3 Choong-Hyun Lee, In Koo Hwang, Jong-Dai Kim, Il Jun Kang, Jun Hwi Cho, Bich Na Shin, Yang Hee Kim, Yun Lyul Lee, Seung Min Park
    2017, 12 (2):  220-227.  doi: 10.4103/1673-5374.200805
    Abstract ( 303 )   PDF (1811KB) ( 739 )   Save

    Quercetin (QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.

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    Electroacupuncture-induced neuroprotection against focal cerebral ischemia in the rat is mediated by adenosine A1 receptors
    Qin-xue Dai, Wu-jun Geng, Xiu-xiu Zhuang, Hong-fa Wang, Yun-chang Mo, He Xin, Jiang-fan Chen, Jun-lu Wang
    2017, 12 (2):  228-234.  doi: 10.4103/1673-5374.200806
    Abstract ( 292 )   PDF (1316KB) ( 803 )   Save

    The activation of adenosine A1 receptors is important for protecting against ischemic brain injury and pretreatment with electroacupuncture has been shown to mitigate ischemic brain insult. The aim of this study was to test whether the adenosine A1 receptor mediates electroacupuncture pretreatment-induced neuroprotection against ischemic brain injury. We first performed 30 minutes of electroacupuncture pretreatment at the Baihui acupoint (GV20), delivered with a current of 1 mA, a frequency of 2/15 Hz, and a depth of 1 mm. High-performance liquid chromatography found that adenosine triphosphate and adenosine levels peaked in the cerebral cortex at 15 minutes and 120 minutes after electroacupuncture pretreatment, respectively. We further examined the effect of 15 or 120 minutes electroacupuncture treatment on ischemic brain injury in a rat middle cerebral artery-occlusion model. We found that at 24 hours reperfusion,120 minutes after electroacupuncture pretreatment, but not for 15 minutes, significantly reduced behavioral deficits and infarct volumes. Last, we demonstrated that the protective effect gained by 120 minutes after electroacupuncture treatment before ischemic injury was abolished by pretreatment with the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 mg/kg, intraperitoneally). Our results suggest that pretreatment with electroacupuncture at the Baihui acupoint elicits protection against transient cerebral ischemia via action at adenosine A1 receptors.

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    3′-Daidzein sulfonate sodium improves mitochondrial functions after cerebral ischemia/reperfusion injury
    Wa Yuan, Qin Chen, Jing Zeng, Hai Xiao, Zhi-hua Huang, Xiao Li, Qiong Lei
    2017, 12 (2):  235-241.  doi: 10.4103/1673-5374.200807
    Abstract ( 274 )   PDF (832KB) ( 842 )   Save

    3′-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein (an active ingredient of the kudzu vine root). It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3′-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3′-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3′-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3′-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.

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    A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits
    Jing-ning Yang, Jun Chen, Min Xiao
    2017, 12 (2):  242-249.  doi: 10.4103/1673-5374.199011
    Abstract ( 276 )   PDF (957KB) ( 787 )   Save

    Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1 (PAR1). However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004 (3 mg/kg) 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.

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    Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients
    Ting-ting Tan, Dan Wang, Ju-ke Huang, Xiao-mei Zhou, Xu Yuan, Jiu-ping Liang, Liang Yin, Hong-liang Xie, Xin-yan Jia, Jiao Shi, Fang Wang, Hao-bo Yang, Shang-jie Chen
    2017, 12 (2):  250-258.  doi: 10.4103/1673-5374.200808
    Abstract ( 341 )   PDF (567KB) ( 683 )   Save

    Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taixi (KI3), Fenglong (ST40), and Taichong (LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed,and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

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    DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children
    Yun Chen, Hua Zhao, Yi-xin Zhang, Peng-xiang Zuo
    2017, 12 (2):  259-266.  doi: 10.4103/1673-5374.200809
    Abstract ( 311 )   PDF (582KB) ( 1688 )   Save

    Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms (rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266) in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models (Codominant, Dominant, Recessive, Heterozygote advantage, and Allele) between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs (rs807724, rs2274305, and rs4599626) were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype (rs9295619-rs807701-rs807724-rs2274305) and the T-A of the two-marker haplotype (rs3765502-1087266) were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

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    Tanshinone IIA improves functional recovery in spinal cord injury-induced lower urinary tract dysfunction
    Yong-dong Yang, Xing Yu, Xiu-mei Wang, Xiao-hong Mu, Feng He
    2017, 12 (2):  267-275.  doi: 10.4103/1673-5374.200810
    Abstract ( 340 )   PDF (2078KB) ( 769 )   Save

    Tanshinone IIA, extracted from Salvia miltiorrhiza Bunge, exerts neuroprotective effects through its anti-inflammatory, anti-oxidative and anti-apoptotic properties. This study intravenously injected tanshinone IIA 20 mg/kg into rat models of spinal cord injury for 7 consecutive days. Results showed that tanshinone IIA could reduce the inflammation, edema as well as compensatory thickening of the bladder tissue, improve urodynamic parameters, attenuate secondary injury, and promote spinal cord regeneration. The number of hypertrophic and apoptotic dorsal root ganglion (L6–S1) cells was less after treatment with tanshinone IIA. The effects of tanshinone IIA were similar to intravenous injection of 30 mg/kg methylprednisolone. These findings suggested that tanshinone IIA improved functional recovery after spinal cord injury-induced lower urinary tract dysfunction by remodeling the spinal pathway involved in lower urinary tract control.

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    Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase II in spinal cord injury rats
    You-jiang Min, Li-li-qiang Ding, Li-hong Cheng, Wei-ping Xiao, Xing-wei He, Hui Zhang, Zhi-yun Min, Jia Pei
    2017, 12 (2):  276-282.  doi: 10.4103/1673-5374.200811
    Abstract ( 258 )   PDF (1062KB) ( 786 )   Save

    Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK) signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan (GV3), Dazhui (GV14), Zusanli (ST36) and Ciliao (BL32) and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the mRNA and protein expression of Rho-A and Rho-associated kinase II (ROCKII) of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKII. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKII. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of RhoA and ROCKII. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

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    Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response
    Bin Dai, Ting Yan, Yi-xing Shen, You-jia Xu, Hai-bin Shen, Dong Chen, Jin-rong Wang, Shuang-hua He, Qi-rong Dong, Ai-liang Zhang
    2017, 12 (2):  283-289.  doi: 10.4103/1673-5374.199006
    Abstract ( 283 )   PDF (1116KB) ( 730 )   Save

    We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R) induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2α) and activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM) treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p)-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

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    Adenyl cyclase activator forskolin protects against Huntington’s disease-like neurodegenerative disorders
    Sidharth Mehan, Shaba Parveen, Sanjeev Kalra
    2017, 12 (2):  290-300.  doi: 10.4103/1673-5374.200812
    Abstract ( 241 )   PDF (1693KB) ( 748 )   Save

    Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington’s disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination (grip strength, beam crossing task, locomotor activity), resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington’s disease-like neurodegeneration.

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    Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular mechanism in the senescence-accelerated mouse prone
    Ying-hong Li, Xu-sheng Wang, Xiao-lin Chen, Yu Jin, Hong-bo Chen, Xiu-qin Jia, Yong-feng Zhang, Zheng-zhi Wu
    2017, 12 (2):  301-306.  doi: 10.4103/1673-5374.200813
    Abstract ( 259 )   PDF (1940KB) ( 790 )   Save

    Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimer’s disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer’s disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer’s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

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    Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors"
    Nathanael J. Yates, Marcus K. Giacci, Ryan L. O’Hare Doig, Wissam Chiha, Bethany E. Ashworth, Jade Kenna, Carole A. Bartlett, Melinda Fitzgerald
    2017, 12 (2):  307-316.  doi: 10.4103/1673-5374.200814
    Abstract ( 242 )   PDF (2657KB) ( 691 )   Save

    Studies have shown that a combined application of several ion channel inhibitors immediately after central nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long after injury the combined treatment of several ion channel inhibitors can be delayed and efficacy maintained. In this study, we delivered Ca2+ entry-inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury site via an iPRECIO@ pump immediately, 6 hours, 24 hours and 7 days after partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hydrochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a significant proportion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca2+ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas.

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    The cortical activation pattern during bilateral arm raising movements
    Sung Ho Jang, Jung Pyo Seo, Seung-Hyun Lee, Sang-Hyun Jin, Sang Seok Yeo
    2017, 12 (2):  317-320.  doi: 10.4103/1673-5374.200817
    Abstract ( 291 )   PDF (600KB) ( 580 )   Save

    Bilateral arm raising movements have been used in brain rehabilitation for a long time. However, no study has been reported on the effect of these movements on the cerebral cortex. In this study, using functional near infrared spectroscopy (fNIRS), we attempted to investigate cortical activation generated during bilateral arm raising movements. Ten normal subjects were recruited for this study. fNIRS was performed using an fNIRS system with 49 channels. Bilateral arm raising movements were performed in sitting position at the rate of 0.5 Hz. We measured values of oxyhemoglobin and total hemoglobin in five regions of interest: the primary sensorimotor cortex, premotor cortex, supplementary motor area, prefrontal cortex, and posterior parietal cortex. During performance of bilateral arm raising movements, oxyhemoglobin and total hemoglobin values in the primary sensorimotor cortex, premotor cortex, supplementary motor area, and prefrontal cortex were similar, but higher in these regions than those in the prefrontal cortex. We observed activation of the arm somatotopic areas of the primary sensorimotor cortex and premotor cortex in both hemispheres during bilateral arm raising movements. According to this result, bilateral arm raising movements appeared to induce large-scale neuronal activation and therefore arm raising movements would be good exercise for recovery of brain functions.

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    Nonhuman primate models of focal cerebral ischemia
    Jingjing Fan, Yi Li, Xinyu Fu, Lijuan Li, Xiaoting Hao, Shasha Li
    2017, 12 (2):  321-328.  doi: 10.4103/1673-5374.200815
    Abstract ( 237 )   PDF (324KB) ( 768 )   Save

    Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

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    Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation
    Zhi-xin Gao, Jin Rao, Yuan-hai Li
    2017, 12 (2):  329-336.  doi: 10.4103/1673-5374.200816
    Abstract ( 283 )   PDF (278KB) ( 1507 )   Save

    Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

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