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Hiroki Fujisawa, Takumi Numazawa, Minoru Kawamura, Mitsuru Naiki
AIMS: Neurotropin® (NTP), an analgesic for chronic pain, has antihyperalgesic effects in specific alternation of rhythm in temperature (SART)-stressed rats. Previous studies have shown that SART stress induces hyperalgesia, as well as post-translational modification of proteins (including substrates for calpain, a calcium-dependent cysteine protease) in the mesencephalon of rats. To better understand the mechanism of action of NTP, we investigated whether SART stress activates calpain in the mesencephalon of rats and whether NTP inhibits this activation...
December 27, 2016: Life Sciences
Yun Kyoung Ryu, Reilley P Mathena, Sanghee Lim, Minhye Kwak, Michael Xu, Cyrus D Mintz
BACKGROUND: Early postnatal exposure to general anesthetic agents causes a lasting impairment in learning and memory in animal models. One hypothesis to explain this finding is that exposure to anesthetic agents during critical points in neural development disrupts the formation of brain circuitry. Here, we explore the effects of sevoflurane on the neuronal growth cone, a specialization at the growing end of axons and dendrites that is responsible for the targeted growth that underlies connectivity between neurons...
October 2016: Journal of Neurosurgical Anesthesiology
Shunsuke Nishimoto, Kiyoshi Okada, Hiroyuki Tanaka, Michio Okamoto, Hiroki Fujisawa, Tomoyuki Okada, Mitsuru Naiki, Tsuyoshi Murase, Hideki Yoshikawa
Neuropathic pain caused by nerve damage in the central and/or peripheral nervous systems is a refractory disorder and the management of such chronic pain has become a major issue. Neurotropin is a drug widely used in Japan and China to treat chronic pain. Although Neurotropin has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the mechanism of analgesic action in the peripheral nervous system remains to be elucidated. In this study, we investigated the local effects of Neurotropin on peripheral nerve damage in a chronic constriction injury (CCI) model...
July 2016: Biologicals: Journal of the International Association of Biological Standardization
Stéphanie Hostenbach, Miguel D'haeseleer, Ron Kooijman, Jacques De Keyser
In the normal central nervous system, endothelin-1 (ET-1) is found in some types of neurons, epithelial cells of the choroid plexus, and endothelial cells of microvessels, but it is usually not detectable in glial cells. However, in different pathological conditions, astrocytes adapting a reactive phenotype express high levels of ET-1 and its receptors, mainly the ETB receptor. ET-1 released by reactive astrocytes appears mainly to have neurodeleterious effects by mechanisms that include constriction of cerebral arterioles leading to impairment of the cerebral microcirculation, increase of blood brain barrier permeability, inflammation, excitotoxicity, impairment of fast axonal transport, and astrogliosis...
September 2016: Progress in Neurobiology
Chiaki Murayama, Shimpei Watanabe, Motokazu Nakamura, Hisayoshi Norimoto
Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly...
August 14, 2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hisashi Okai, Ryohei Okazaki, Minoru Kawamura, Megumu Yoshimura
AIMS: Although the clinical use of Neurotropin® as an analgesic for chronic pain has been firmly established, its analgesic mechanism is still unclear. In this study, we investigate the direct effects of Neurotropin using an electrophysiological method. MAIN METHODS: Blind patch-clamp recordings were made from rat locus coeruleus (LC) and periaqueductal gray (PAG) neurons in brainstem slices of normal rats. The effects of intracerebroventricular (icv) injection of Neurotropin on nociceptive transmission were recorded from spinal substantia gelatinosa (SG) neurons in fifth lumbar spinal nerve-ligated (L5-SNL) rats using an in vivo patch-clamp method...
September 1, 2015: Life Sciences
Harvey J Armbrecht, Akbar M Siddiqui, Michael Green, Susan A Farr, Vijaya B Kumar, William A Banks, Ping Patrick, Gul N Shah, John E Morley
The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accompanied by an increase in hippocampal amyloid-β protein precursor (AβPP) and amyloid-β peptide (Aβ). We have shown that administration of an antisense oligonucleotide against the Aβ region of AβPP (AβPP antisense) reverses the memory deficits. The purpose of this study was to determine the effect of peripheral (IV) administration of AβPP antisense on hippocampal gene expression. The AβPP antisense reversed the memory deficits and altered expression of 944 hippocampal genes...
2015: Journal of Alzheimer's Disease: JAD
Bi Zhang, Yoon Seok Roh, Shuang Liang, Cheng Liu, Mitsuru Naiki, Koichi Masuda, Ekihiro Seki
Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes...
2014: PloS One
Yu Fukuda, Takao Fukui, Chika Hikichi, Tomomasa Ishikawa, Kenichiro Murate, Takeshi Adachi, Hideki Imai, Koki Fukuhara, Akihiro Ueda, Allen P Kaplan, Tatsuro Mutoh
Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity...
January 30, 2015: Brain Research
Toshizo Ishikawa, Seiko Yasuda, Seiji Minoda, Takae Ibuki, Kayoko Fukuhara, Yasutake Iwanaga, Toru Ariyoshi, Hironori Sasaki
Neurotropin (NTP)(®), a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, is used clinically for the treatment of neuropathic pain. Moreover, NTP may activate the descending pain inhibitory system. Depression-like behavior is often complicated by chronic pain. However, little is known about NTP-mediated prevention of mood disorders in chronic pain and its molecular mechanisms. We aimed to investigate the effects of NTP on brain-derived neurotrophic factor (BDNF)-mediated signaling and gene expression in chronic pain...
March 2015: Cellular and Molecular Neurobiology
Abbie L A Binch, Ashley A Cole, Lee M Breakwell, Anthony L R Michael, Neil Chiverton, Alison K Cross, Christine L Le Maitre
INTRODUCTION: The degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells. METHODS: Quantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors...
2014: Arthritis Research & Therapy
Sarita Bajaj, Raj Pratap Singh, N C Dwivedi, Kamaljeet Singh, Arvind Gupta, Manoj Mathur
BACKGROUND: Vitamin D has important actions on glucose metabolism. These include improved insulin exocytosis, direct stimulation of insulin receptor, improved uptake of glucose by peripheral tissues, improving insulin resistance. It has got various pleiotropic effects like suppression of cell mediated immunity, regulation of cell proliferation, stimulation of neurotropic factors such as nerve growth factor, Glial cell line-derived neurotrophic factor, neurotropin, suppression of RAAS, reduction of albuminuria, immunomodulatory effects, and anti-inflammatory effects...
July 2014: Indian Journal of Endocrinology and Metabolism
Joseph P Steiner, Avindra Nath
As people are living longer, the prevalance of neurodegenerative diseases continues to rise resulting in huge socio-economic consequences. Despite major advancements in studying the pathophysiology of these diseases and a large number of clinical trials currently there is no effective treatment for these illnesses. All neuroprotective strategies have either failed or have shown only a minimal effect. There has been a major shift in recent years exploring the potential of neuroregenerative approaches. While the concept of using neurotropins for therapeutic purposes has been in existence for many years, new modes of delivery and expression of this family of molecules makes this approach now feasilble...
March 2014: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Ken Masuguchi, Hitomi Watanabe, Takehiro Kawashiri, Soichiro Ushio, Nana Ozawa, Haruka Morita, Ryozo Oishi, Nobuaki Egashira
AIMS: Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic peripheral neuropathies. We previously reported that repeated administration of neurotropin prevents oxaliplatin-induced mechanical allodynia by inhibiting axonal degeneration in rats. In the present study, we investigated the analgesic effect of a single administration of neurotropin on oxaliplatin-induced neuropathy in rats. MAIN METHODS: Oxaliplatin (4mg/kg) was administered intraperitoneally twice a week for 4weeks...
March 7, 2014: Life Sciences
L Yang, J Chao, Y H Kook, Y Gao, H Yao, S J Buch
Highly conserved microRNA-9 (miR-9) has a critical role in various cellular processes including neurogenesis. However, its regulation by neurotropins that are known to mediate neurogenesis remains poorly defined. In this study, we identify platelet-derived growth factor-BB (PDGF-BB)-mediated upregulation of miR-9, which in turn downregulates its target gene monocyte chemotactic protein-induced protein 1 (MCPIP1), as a key player in modulating proliferation, neuronal differentiation as well as migration of neuronal progenitor cells (NPCs)...
December 12, 2013: Cell Death & Disease
Yun-Xiao Sun, Jian Yang, Ping-Yu Wang, You-Jie Li, Shu-Yang Xie, Ruo-Peng Sun
Brain-derived neurotropic factor (BDNF) is a member of the neurotropin family. High levels of BDNF are associated with more aggressive malignant behavior in human cancer. In the present study, we observed the effect of cisplatin on BDNF expression in SH-SY5Y cells and investigated the mechanism of cisplatin in inducing the apoptosis of SH-SY5Y cells. Our results revealed that the expression of BDNF was obviously decreased in cisplatin-treated SH-SY5Y cells. In addition, the 3'-untranslated region of BDNF was found to be targeted by miR-16 using microRNA analysis software...
November 2013: Oncology Reports
A Kamo, M Tominaga, K Taneda, H Ogawa, K Takamori
Epidermal hyperinnervation is considered one cause of sensitization to itch, and is thought to regulated by keratinocyte-derived axonal guidance molecules, including nerve growth factor (NGF) and semaphorin (Sema)3A. Neurotropin (NTP) shows antipruritic effects in allergic disease and is also used for pain relief. Using cultured rat dorsal root ganglion neurones, we previously found that NTP inhibited NGF-induced neurite outgrowth. However, no such inhibitory effect has been shown in vivo. We therefore assessed the effects of intraperitoneal administration of NTP on nerve density and expression of NGF and Sema3A mRNAs in the epidermis of acetone-treated mice showing epidermal hyperinnervation...
August 2013: Clinical and Experimental Dermatology
Risa Isonaka, Tamie Takenami, Takashi Katakura, Tadashi Kawakami
Axonal transport is a basic neuronal cell function and important for the supply of materials that maintain neuronal cells, and any increase or decrease in axonal transport expresses the state of neurons. Neurotropin is an analgesic agent commonly used for the treatment of chronic pain, but its mechanism of action remains not fully understood. The effects of neurotropin have been investigated in various animal models of nerve injury and chronic pain. In the present study, we dissected the effects of neurotropin on sensory neurons with a special focus on axonal transport using cultured mouse dorsal root ganglion (DRG) neurons...
May 24, 2013: Neuroscience Letters
Marian Kacerovsky, Peter Celec, Barbora Vlkova, Kristin Skogstrand, David M Hougaard, Teresa Cobo, Bo Jacobsson
OBJECTIVE: This study aimed to evaluate the amniotic fluid protein profiles and the intensity of intraamniotic inflammatory response to Ureaplasma spp. and other bacteria, using the multiplex xMAP technology. METHODS: A retrospective cohort study was undertaken in the Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Czech Republic. A total of 145 pregnant women with preterm prelabor rupture of membranes between gestational age 24+0 and 36+6 weeks were included in the study...
2013: PloS One
Yuko Kanbayashi, Toyoshi Hosokawa, Jo Kitawaki, Tetsuya Taguchi
AIM: The aim of this study was to identify predictors for paclitaxel-induced peripheral neuropathy (PIPN). PATIENTS AND METHODS: We conducted a retrospective analysis of 227 patients who had been treated with paclitaxel at a single institution between January 2008 and July 2011. At the time of chemotherapy completion, the severity of PIPN was graded on a scale of 0-5, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4...
March 2013: Anticancer Research
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