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https://www.readbyqxmd.com/read/28339401/is-huntingtin-dispensable-in-the-adult-brain
#1
Jeh-Ping Liu, Scott O Zeitlin
Huntingtin (HTT) is an essential protein during early embryogenesis and the development of the central nervous system (CNS). Conditional knock-out of mouse Huntingtin (Htt) expression in the CNS beginning during neural development, as well as reducing Htt expression only during embryonic and early postnatal stages, results in neurodegeneration in the adult brain. These findings suggest that HTT is important for the development and/or maintenance of the CNS, but they do not address the question of whether HTT is required specifically in the adult CNS for its normal functions and/or homeostasis...
March 21, 2017: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/28335495/brain-derived-neurotrophic-factor-loaded-ps80-pbca-nanocarrier-for-in-vitro-neural-differentiation-of-mouse-induced-pluripotent-stem-cells
#2
Chiu-Yen Chung, Martin Hsiu-Chu Lin, I-Neng Lee, Tsong-Hai Lee, Ming-Hsueh Lee, Jen-Tsung Yang
Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting...
March 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28333135/bre-modulates-granulosa-cell-death-to-affect-ovarian-follicle-development-and-atresia-in-the-mouse
#3
Cheung Kwan Yeung, Guang Wang, Yao Yao, Jianxin Liang, Cheuk Yiu Tenny Chung, Manli Chuai, Kenneth Ka Ho Lee, Xuesong Yang
The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28327087/nt5c2-novel-splicing-variant-expands-the-phenotypic-spectrum-of-spastic-paraplegia-spg45-case-report-of-a-new-member-of-thin-corpus-callosum-spg-subgroup
#4
Mahmoud F Elsaid, Khalid Ibrahim, Nader Chalhoub, Ahmed Elsotouhy, Noora El Mudehki, Alice Abdel Aleem
BACKGROUND: Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative diseases. Thin Corpus Callosum (TCC) associated HSP is a distinguished subgroup of complex forms. Purines and pyrimidine, the basic DNA and RNA components, are regulating the cell metabolism, having roles in signal transduction, energy preservation and cellular repair. Genetic defects in nucleotide metabolism related genes have been only recently implicated in brain and neurodegenerative diseases' pathogenesis...
March 21, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28326018/neuronal-nitric-oxide-synthase-in-neural-stem-cells-induces-neuronal-fate-commitment-via-the-inhibition-of-histone-deacetylase-2
#5
Xing Jin, Zhang-Feng Yu, Fang Chen, Guang-Xian Lu, Xin-Yuan Ding, Lin-Jun Xie, Jian-Tong Sun
Active adult neurogenesis produces new functional neurons, which replace the lost ones and contribute to brain repair. Promoting neurogenesis may offer a therapeutic strategy for human diseases associated with neurodegeneration. Here, we report that endogenous neuronal nitric oxide synthase (nNOS) for neural stem cells (NSCs) or progenitors positively regulates neurogenesis. nNOS repression exhibits significantly decreased neuronal differentiation and nNOS upregulation promotes neurons production from NSCs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28323540/identification-of-multipotent-stem-cells-in-human-brain-tissue-following-stroke
#6
Kotaro Tatebayashi, Yasue Tanaka, Akiko Nakano-Doi, Rika Sakuma, Saeko Kamachi, Manabu Shirakawa, Kazutaka Uchida, Hiroto Kageyama, Toshinori Takagi, Shinichi Yoshimura, Tomohiro Matsuyama, Takayuki Nakagomi
Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice, and that these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the post-stroke human brain for possible applications in stem cell-based therapies for stroke patients. Here we report for the first time that iSCs can be isolated from the post-stroke human brain...
March 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28322920/stem-cell-transplantation-therapy-for-multifaceted-therapeutic-benefits-after-stroke
#7
REVIEW
Ling Wei, Zheng Z Wei, Michael Qize Jiang, Osama Mohamad, Shan Ping Yu
One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures...
March 16, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28315865/proteomic-analysis-of-mouse-cortex-postsynaptic-density-following-neonatal-brain-hypoxia-ischemia
#8
Guo Shao, Yongqiang Wang, Shenheng Guan, Alma L Burlingame, Fuxin Lu, Renatta Knox, Donna M Ferriero, Xiangning Jiang
Proteomics of the synapses and postsynaptic densities (PSDs) have provided a deep understanding of protein composition and signal networks in the adult brain, which underlie neuronal plasticity and neurodegenerative or psychiatric disorders. However, there is a paucity of knowledge about the architecture and organization of PSDs in the immature brain, and how it is modified by brain injury in an early developing stage. Mass spectrometry (MS)-based proteomic analysis was performed on PSDs prepared from cortices of postnatal day 9 naïve mice or pups which had suffered hypoxic-ischemic (HI) brain injury...
March 18, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28315294/neuronal-cell-sheet-of-cortical-motor-neuron-phenotype-derived-from-human-ips-cells
#9
Noboru Suzuki, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Chieko Hirotsu, Erika Takada, Yuji Ueda, Sueshige Wakisaka, Naruyoshi Fujiwara, Tomoko Suzuki
<p>Transplantation of stem cells which differentiate into more mature neural cells brings about functional improvement in pre-clinical studies of stroke. Previous transplant approaches in diseased brain have utilized injection of the cells in a cell suspension. In addition, neural stem cells were preferentially used as graft. However, these cells had no specific relationship to the damaged tissue of stroke patients and brain injury. The injection of cells in a suspension destroyed the cell-cell interactions that are suggested to be important for promoting functional integrity as cortical motor neurons...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#10
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28304184/chronic-stress-induced-disruption-of-the-peri-infarct-neurovascular-unit-following-experimentally-induced-photothrombotic-stroke
#11
Zidan Zhao, Lin Kooi Ong, Sarah Johnson, Michael Nilsson, Frederick R Walker
How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28303914/restoring-brain-function-after-stroke-bridging-the-gap-between-animals-and-humans
#12
REVIEW
Nick S Ward
Stroke is the leading cause of complex adult disability in the world. Recovery from stroke is often incomplete, which leaves many people dependent on others for their care. The improvement of long-term outcomes should, therefore, be a clinical and research priority. As a result of advances in our understanding of the biological mechanisms involved in recovery and repair after stroke, therapeutic opportunities to promote recovery through manipulation of poststroke plasticity have never been greater. This work has almost exclusively been carried out in preclinical animal models of stroke with little translation into human studies...
March 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28303738/neural-stem-cell-transplantation-in-ischemic-stroke-a-role-for-preconditioning-and-cellular-engineering
#13
Joshua D Bernstock, Luca Peruzzotti-Jametti, Daniel Ye, Florian A Gessler, Dragan Maric, Nunzio Vicario, Yang-Ja Lee, Stefano Pluchino, John M Hallenbeck
Ischemic stroke continues to be a leading cause of morbidity and mortality throughout the world. To protect and/or repair the ischemic brain, a multitiered approach may be centered on neural stem cell (NSC) transplantation. Transplanted NSCs exert beneficial effects not only via structural replacement, but also via immunomodulatory and/or neurotrophic actions. Unfortunately, the clinical translation of such promising therapies remains elusive, in part due to their limited persistence/survivability within the hostile ischemic microenvironment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28300134/white-matter-repair-after-extracellular-vesicles-administration-in-an-experimental-animal-model-of-subcortical-stroke
#14
Laura Otero-Ortega, Fernando Laso-García, María Del Carmen Gómez-de Frutos, Berta Rodríguez-Frutos, Jorge Pascual-Guerra, Blanca Fuentes, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299949/postnatal-neural-stem-cells
#15
Vanessa Donega, Olivier Raineteau
There is growing evidence for a tentative cellular repair in the forebrain following perinatal injuries. In this review, we present the evidences and shortcomings in this regenerative attempt. We discuss recent progress in elucidating the origin, diversity, and competence of postnatal neural stem cells/progenitor cells. Finally, we propose new strategies to recruit postnatal progenitors to generate specific subtypes of cortical neurons or oligodendrocytes, thereby allowing the development of tailor-made approaches to treat perinatal brain injuries...
March 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28294555/promise-and-peril-in-nanomedicine-the-challenges-and-needs-for-integrated-systems-biology-approaches-to-define-health-risk
#16
REVIEW
Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Carole L Yauk
In the 1966s visionary film 'Fantastic Voyage' a submarine crew was shrunk to 100 nm in size and injected into the body of an injured scientist to repair his damaged brain. The movie (written by Harry Kleiner; directed by Richard Fleischer; novel by Isaac Asimov) drew attention to the potential power of engineered nanoscale structures and devices to construct, monitor, control, treat, and repair individual cells. Even more interesting was the fact that the film elegantly noted that the structure had to be miniaturized to a size that is not detected by the body's immune surveillance system, and highlighted the many physiological barriers that are encountered on the submarine's long journey to the target...
March 15, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28293764/immune-checkpoint-inhibition-and-its-relationship-with-hypermutation-phenoytype-as-a-potential-treatment-for-glioblastoma
#17
REVIEW
Manohan Sinnadurai, Kerrie L McDonald
Glioblastoma (GBM) is the most common malignant brain tumour in adults. Current prognosis with standard treatment is poor. Immunotherapy is a new paradigm in tumour management. Specifically, recent advances in the field of immune checkpoint molecules have led to dramatic results in many cancers. Inhibition of one particular, programmed cell death-1 (PD-1) has recently been shown to be highly effective in melanoma and non-small cell lung cancer. There has also been recent data to suggest potential benefit in GBM...
March 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28293177/mscs-derived-exosomes-and-neuroinflammation-neurogenesis-and-therapy-of-traumatic-brain-injury
#18
REVIEW
Yongxiang Yang, Yuqin Ye, Xinhong Su, Jun He, Wei Bai, Xiaosheng He
Exosomes are endosomal origin membrane-enclosed small vesicles (30-100 nm) that contain various molecular constituents including proteins, lipids, mRNAs and microRNAs. Accumulating studies demonstrated that exosomes initiated and regulated neuroinflammation, modified neurogenic niches and neurogenesis, and were even of potential significance in treating some neurological diseases. These tiny extracellular vesicles (EVs) can derive from some kinds of multipotent cells such as mesenchymal stem cells (MSCs) that have been confirmed to be a potentially promising therapy for traumatic brain injury (TBI) in experimental models and in preclinical studies...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28290152/vascular-endothelial-growth-factor-isoform-b-stimulates-neurovascular-repair-after-ischemic-stroke-by-promoting-the-function-of-pericytes-via-vascular-endothelial-growth-factor-receptor-1
#19
Noëmie Jean LeBlanc, Revathy Guruswamy, Ayman ElAli
Ischemic stroke triggers endogenous angiogenic mechanisms, which correlates with longer survival in patients. As such, promoting angiogenesis appears to be a promising approach. Experimental studies investigated mostly the potent angiogenic factor vascular endothelial growth factor isoform-A (VEGF-A). However, VEGF-A increases the risk of destabilizing the brain microvasculature, thus hindering the translation of its usage in clinics. An attractive alternative VEGF isoform-B (VEGF-B) was recently reported to act as a survival factor rather than a potent angiogenic factor...
March 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28287992/spanner-a-self-repairing-spiking-neural-network-hardware-architecture
#20
Junxiu Liu, Jim Harkin, Liam P Maguire, Liam J McDaid, John J Wade
Recent research has shown that a glial cell of astrocyte underpins a self-repair mechanism in the human brain, where spiking neurons provide direct and indirect feedbacks to presynaptic terminals. These feedbacks modulate the synaptic transmission probability of release (PR). When synaptic faults occur, the neuron becomes silent or near silent due to the low PR of synapses; whereby the PRs of remaining healthy synapses are then increased by the indirect feedback from the astrocyte cell. In this paper, a novel hardware architecture of Self-rePAiring spiking Neural NEtwoRk (SPANNER) is proposed, which mimics this self-repairing capability in the human brain...
March 6, 2017: IEEE Transactions on Neural Networks and Learning Systems
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