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https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#1
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28720882/cell-type-specific-differences-in-promoter-activity-of-the-als-linked-c9orf72-mouse-ortholog
#2
Abraham J Langseth, Juhyun Kim, Janet E Ugolino, Yajas Shah, Ho-Yon Hwang, Jiou Wang, Dwight E Bergles, Solange P Brown
A hexanucleotide repeat expansion in the C9orf72 gene is the most common cause of inherited forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Both loss-of-function and gain-of-function mechanisms have been proposed to underlie this disease, but the pathogenic pathways are not fully understood. To better understand the involvement of different cell types in the pathogenesis of ALS, we systematically analyzed the distribution of promoter activity of the mouse ortholog of C9orf72 in the central nervous system...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715117/differential-activation-of-neuronal-and-glial-stat3-in-the-spinal-cord-of-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#3
Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno
Signal transducer and activator of transcription (STAT) proteins are activated by phosphorylation in the spinal cord of patients suffering from amyotrophic lateral sclerosis (ALS). The major scope of our study is a comprehensive histological characterization of the mechanisms underlying neuronal and glial STAT3 activation in the pathogenesis of ALS using SOD1(G93A) mice. We calculated the fold changes (FCs, ratios vs. appropriate controls) of the numerical densities of the following phosphorylated STAT3-positive (pSTAT3)(+) cells: choline acetyltransferase (ChAT)(+) α-motoneurons, ionized calcium-binding adapter molecule 1 (Iba1)(+) microglia, and S100β(+) astrocytes in SOD1(G93A) mice...
July 17, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28714852/the-small-molecule-mimetic-agonist-trimebutine-of-adhesion-molecule-l1-contributes-to-functional-recovery-after-spinal-cord-injury-in-mice
#4
Junping Xu, Chengliang Hu, Qiong Jiang, Hongchao Pan, Huifan Shen, Melitta Schachner
Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity, and thus constitutes a viable target to promote regeneration after SCI. Since delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans, we have identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration, and neurite outgrowth in an L1-dependent manner...
July 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28707354/additive-neurogenesis-supported-by-multiple-stem-cell-populations-mediates-adult-spinal-cord-development-a-spatio-temporal-statistical-mapping-analysis-in-a-teleost-model-of-indeterminate-growth
#5
Ruxandra F Sîrbulescu, Iulian Ilieş, Annette Meyer, Günther K H Zupanc
The knifefish Apteronotus leptorhynchus exhibits indeterminate growth throughout adulthood. This phenomenon extends to the spinal cord, presumably through the continuous addition of new neurons and glial cells. However, little is known about the developmental dynamics of cells added during adult growth. The present work characterizes the structural and functional development of the adult spinal cord in this model organism through a comprehensive quantitative analysis of the spatial and temporal dynamics of new cells at various developmental stages...
July 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28705495/glial-associated-changes-in-the-cerebral-cortex-after-collagenase-induced-intracerebral-hemorrhage-in-the-rat-striatum
#6
J D Neves, D Aristimunha, A F Vizuete, F Nicola, C Vanzela, L Petenuzzo, R G Mestriner, E F Sanches, C A Gonçalves, C A Netto
Striatum and the cerebral cortex are regions susceptible to secondary injury after intracerebral hemorrhage (ICH) and glial cells in tissue adjacent to the hematoma may modulate cellular vulnerability after brain damage. Nonetheless, while the glial- associated changes occurring in the cerebral cortex after ICH may be important in maximizing brain recovery, they are not fully understood. The aim of this study was to evaluate the temporal profile of glial-associated changes in the cerebral cortex after ICH. First, the motor consequences of ICH and its relation to the lesion volume were analyzed...
July 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28696309/influenza-infection-triggers-disease-in-a-genetic-model-of-experimental-autoimmune-encephalomyelitis
#7
Stephen Blackmore, Jessica Hernandez, Michal Juda, Emily Ryder, Gregory G Freund, Rodney W Johnson, Andrew J Steelman
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we used an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS, and trigger disease...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695279/epigenetic-regulation-of-neural-stem-cell-differentiation-towards-spinal-cord-regeneration
#8
REVIEW
Tomonori Kameda, Takuya Imamura, Kinichi Nakashima
Severe spinal cord injury (SCI) leads to almost complete neural cell loss at the injured site, causing the irreversible disruption of neuronal circuits. The transplantation of neural stem or precursor cells (NS/PCs) has been regarded as potentially effective for SCI treatment because NS/PCs can compensate for the injured sites by differentiating into neurons and glial cells (astrocytes and oligodendrocytes). An understanding of the molecular mechanisms that regulate the proliferation, fate specification and maturation of NS/PCs and their progeny would facilitate the establishment of better therapeutic strategies for regeneration after SCI...
July 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28687401/pathophysiological-role-of-prostaglandin-e2-induced-up-regulation-of-the-ep2-receptor-in-motor-neuron-like-nsc-34-cells-and-lumbar-motor-neurons-in-als-model-mice
#9
Yasuhiro Kosuge, Hiroko Miyagishi, Yuki Yoneoka, Keiko Yoneda, Hiroshi Namgo, Kumiko Ishige, Yoshihisa Ito
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice...
July 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28680400/a-novel-small-molecule-gdnf-receptor-ret-agonist-bt13-promotes-neurite-growth-from-sensory-neurons-in-vitro-and-attenuates-experimental-neuropathy-in-the-rat
#10
Yulia A Sidorova, Maxim M Bespalov, Agnes W Wong, Oleg Kambur, Viljami Jokinen, Tuomas O Lilius, Ilida Suleymanova, Gunnar Karelson, Pekka V Rauhala, Mati Karelson, Peregrine B Osborne, Janet R Keast, Eija A Kalso, Mart Saarma
Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28676785/atypical-teratoid-rhabdoid-tumor-two-case-reports-and-an-analysis-of-adult-cases-with-implications-for-pathophysiology-and-treatment
#11
Christopher Dardis, Jared Yeo, Kelly Milton, Lynn S Ashby, Kris A Smith, Shwetal Mehta, Emad Youssef, Jenny Eschbacher, Kathy Tucker, Laughlin Dawes, Neil Lambie, Elizabeth Algar, Elizabeth Hovey
We present the first quantitative analysis of atypical teratoid rhabdoid tumors (ATRT) in adults, including two patients from our own institutions. These are of interest as one occurred during pregnancy and one is a long-term survivor. Our review of pathological findings of 50 reported cases of adult ATRT leads us to propose a solely ectodermal origin for the tumor and that epithelial-mesenchymal transition (EMT) is a defining feature. Thus, the term ATRT may be misleading. Our review of clinical findings shows that ATRT tends to originate in mid-line structures adjacent to the CSF, leading to a high rate of leptomeningeal dissemination...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28668379/design-and-optimization-of-plga-microparticles-for-controlled-and-local-delivery-of-neuregulin-1-in-traumatic-spinal-cord-injury
#12
Kallivalappil T Santhosh, Arsalan Alizadeh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in significant tissue damage that underlies functional impairments. Pharmacological interventions to confer neuroprotection and promote cell replacement are essential for SCI repair. We previously reported that Neuregulin-1 (Nrg-1) is acutely and permanently downregulated after SCI. Nrg-1 is a critical growth factor for differentiation of neural precursor cells (NPCs) into myelinating oligodendrocytes. We showed that intrathecal delivery of Nrg-1 enhances oligodendrocyte replacement following SCI...
June 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28658046/induction-of-endogenous-neural-stem-cells-by-extracorporeal-shock-waves-after-spinal-cord-injury
#13
Dong-Chul Shin, Kee-Yong Ha, Young-Hoon Kim, Jang-Woon Kim, Yoo-Kyung Cho, Sang-Il Kim
STUDY DESIGN: Animal experimental study OBJECTIVES.: The purpose of this study is to investigate the effects of extracorporeal shock waves (ESWs) on endogenous neural stem cells (NSCs) proliferation after spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Exogenous stem cell transplantation for SCI still has many limitations to be addressed such as ideal cell sources, timing of transplantation, and fate of the transplanted cells. Moreover, the efficacy is another issue due to a peculiar pathologic condition in the chronic phase of SCI...
June 27, 2017: Spine
https://www.readbyqxmd.com/read/28647288/gap-junctions-pannexins-and-pain
#14
REVIEW
David C Spray, Menachem Hanani
Enhanced expression and function of gap junctions and pannexin (Panx) channels has been associated with both peripheral and central mechanisms of pain sensitization. At the level of the sensory ganglia, evidence includes augmented gap junction and pannexin1 expression in glial cells and neurons in inflammatory and neuropathic pain models and increased synchrony and enhanced cross-excitation among sensory neurons by gap junction-mediated coupling. In spinal cord and in suprapinal areas, evidence is largely limited to increased expression of relevant proteins, although in several rodent pain models, hypersensitivity is reduced by treatment with gap junction/Panx1 channel blocking compounds...
June 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28645297/interleukin-1-receptor-type-1-is-overexpressed-in-neurons-but-not-in-glial-cells-within-the-rat-superficial-spinal-dorsal-horn-in-complete-freund-adjuvant-induced-inflammatory-pain
#15
Krisztina Holló, László Ducza, Zoltán Hegyi, Klaudia Dócs, Krisztina Hegedűs, Erzsébet Bakk, Ildikó Papp, Gréta Kis, Zoltán Mészár, Zsuzsanna Bardóczi, Miklós Antal
BACKGROUND: All known biological functions of the pro-inflammatory cytokine interleukin-1β (IL-1β) are mediated by type 1 interleukin receptor (IL-1R1). IL-1β-IL-1R1 signaling modulates various neuronal functions including spinal pain processing. Although the role of IL-1β in pain processing is generally accepted, there is a discussion in the literature whether IL-1β exerts its effect on spinal pain processing by activating neuronal or glial IL-1R1. To contribute to this debate, here we investigated the expression and cellular distribution of IL-1R1 in the superficial spinal dorsal horn in control animals and also in inflammatory pain...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28644072/clinicopathological-and-imaging-features-of-lipoastrocytoma-case-report
#16
Laxminadh Sivaraju, Saritha Aryan, Nandita Ghosal, Alangar S Hegde
Lipidized tumors of the central nervous system are very uncommon, with only a few cases described. We report a case of a 25-year-old woman with a tumor involving the left premotor area. She underwent gross total excision. Histologically, the tumor was composed of glial fibrillary acidic protein-positive glial cells with areas of lipidization. A diagnosis of lipoastrocytoma was rendered. At three-year follow-up she was doing well, supporting the presumed favorable prognosis of these uncommon tumors. Absence of xanthochromic appearance, mitotic activity, necrosis and poor reticulin activity are the differentiating features from the pleomorphic xanthoastrocytoma...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28638936/nuclear-receptors-in-neural-stem-progenitor-cell-homeostasis
#17
REVIEW
Dimitrios Gkikas, Matina Tsampoula, Panagiotis K Politis
In the central nervous system, embryonic and adult neural stem/progenitor cells (NSCs) generate the enormous variety and huge numbers of neuronal and glial cells that provide structural and functional support in the brain and spinal cord. Over the last decades, nuclear receptors and their natural ligands have emerged as critical regulators of NSC homeostasis during embryonic development and adult life. Furthermore, substantial progress has been achieved towards elucidating the molecular mechanisms of nuclear receptors action in proliferative and differentiation capacities of NSCs...
June 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28638088/chemokine-receptor-cxcr4-regulates-camkii-creb-pathway-in-spinal-neurons-that-underlies-cancer-induced-bone-pain
#18
Xue-Ming Hu, Hui Zhang, Heng Xu, Hai-Long Zhang, Li-Ping Chen, Wen-Qiang Cui, Wei Yang, Wen Shen
We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637974/neuron-glia-interaction-is-a-key-mechanism-underlying-persistent-orofacial-pain
#19
Koichi Iwata, Ayano Katagiri, Masamichi Shinoda
Excitability of neurons in the trigeminal ganglion (TG), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (C1-C2) is greatly enhanced after orofacial inflammation and trigeminal nerve injury, and TG, Vc, and C1-C2 neurons remain sensitized long after such episodes. Sensitized neurons generate various molecules, which are released from nociceptive neurons in these areas and are involved in modulating the excitability of TG, Vc, and C1-C2 nociceptive neurons. Hyperexcitable nociceptive neurons also activate satellite glial cells in the TG and microglial cells and astrocytes in the Vc and C1-C2...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28637335/astrocyte-produced-mir-146a-as-a-mediator-of-motor-neuron-loss-in-spinal-muscular-atrophy
#20
Samantha L Sison, Teresa N Patitucci, Emily R Seminary, Eric Villalon, Christian L Lorson, Allison D Ebert
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by loss of the survival motor neuron-1 (SMN1) gene, which leads to motor neuron loss, muscle atrophy, respiratory distress, and death. Motor neurons exhibit the most profound loss, but the mechanisms underlying disease pathogenesis are not fully understood. Recent evidence suggests that motor neuron extrinsic influences, such as those arising from astrocytes, contribute to motor neuron malfunction and loss. Here we investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a role in SMA pathology...
June 15, 2017: Human Molecular Genetics
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