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https://www.readbyqxmd.com/read/28107370/neuronal-injury-and-glial-changes-are-hallmarks-of-open-field-blast-exposure-in-swine-frontal-lobe
#1
Srinivasu Kallakuri, Alok Desai, Ke Feng, Sharvani Tummala, Tal Saif, Chaoyang Chen, Liying Zhang, John M Cavanaugh, Albert I King
With the rapid increase in the number of blast induced traumatic brain injuries and associated neuropsychological consequences in veterans returning from the operations in Iraq and Afghanistan, the need to better understand the neuropathological sequelae following exposure to an open field blast exposure is still critical. Although a large body of experimental studies have attempted to address these pathological changes using shock tube models of blast injury, studies directed at understanding changes in a gyrencephalic brain exposed to a true open field blast are limited and thus forms the focus of this study...
2017: PloS One
https://www.readbyqxmd.com/read/28106731/hypoxia-inducible-factor-1%C3%AE-promotes-endogenous-adaptive-response-in-rat-model-of-chronic-cerebral-hypoperfusion
#2
Ying Yang, Jieyang Ju, Min Deng, Jing Wang, Hui Liu, Li Xiong, Junjian Zhang
Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#3
Lei Zhao, Jun Li, Yingmei Fu, Mengxue Zhang, Bowen Wang, Jonathan Ouellette, Pawan K Shahi, Bikash R Pattnaik, Jyoti J Watters, Wai T Wong, Lian-Wang Guo
BACKGROUND: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown. METHODS: We employed the rd10 mouse model (Pde6b (rd10) mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28101527/regulation-of-physical-microglia-neuron-interactions-by-fractalkine-signaling-after-status-epilepticus
#4
Ukpong B Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J Margolis, Long-Jun Wu
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#5
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28097612/wip1-phosphatase-plays-a-critical-neuroprotective-role-in-brain-injury-induced-by-high-altitude-hypoxic-inflammation
#6
Dahu Li, Lijun Zhang, Xin Huang, Lili Liu, Yunling He, Lun Xu, Yiyao Zhang, Tong Zhao, Liying Wu, Yongqi Zhao, Kuiwu Wu, Yan Wu, Ming Fan, Lingling Zhu
The hypobaric hypoxic environment in high-altitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear. Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities...
January 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#7
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#8
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low, Jasmine R Dickinson, Chaudy Sotoudeh, J David Clark, Ben A Barres, Christopher J Bohlen, Grégory Scherrer
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28089775/degenerative-effects-of-cobalt-chloride-treatment-on-neurons-and-microglia-in-a-porcine-retina-organ-culture-model
#9
S Kuehn, J Hurst, F Rensinghoff, T Tsai, S Grauthoff, Y Satgunarajah, H B Dick, S Schnichels, S C Joachim
In order to understand the pathological processes of retinal diseases, experimental models are necessary. Cobalt, as part of the vitamin B12 complex, is important for neuronal integrity. However, it is known that high quantities of cobalt induce cytotoxic mechanisms via hypoxia mimicry. Therefore, we tested the degenerative effect of cobalt chloride (CoCl2) on neurons and microglia in a porcine retina organ culture model. Organotypic cultures of porcine retinas were cultured and treated with different concentrations of CoCl2 (0, 100, 300 and 500 μM) for 48 h...
January 12, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28089558/startle-suppression-after-mild-traumatic-brain-injury-is-associated-with-an-increase-in-pro-inflammatory-cytokines-reactive-gliosis-and-neuronal-loss-in-the-caudal-pontine-reticular-nucleus
#10
Swamini P Sinha, Pelin Avcu, Kevin M Spiegler, Sreeya Komaravolu, Kevin Kim, Tara Cominski, Richard J Servatius, Kevin C H Pang
Mild traumatic brain injury (mTBI) can produce somatic symptoms such as headache, dizziness, fatigue, sleep disturbances and sensorimotor dysfunction. Sensorimotor function can be measured by tests such as the acoustic startle reflex (ASR), an evolutionarily conserved defensive response to a brief yet sharp acoustic stimulus. mTBI produces a long-lasting suppression of ASR in rodents and humans; however, the mechanism of this suppression is unknown. The present study examined whether inflammatory processes in the brainstem (particularly the caudal pontine reticular nucleus, PnC) could account for the suppression of ASR after mTBI, because the PnC is an essential nucleus of the ASR circuit...
January 9, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28086916/microglial-activation-in-parkinson-s-disease-using-18-f-feppa
#11
Christine Ghadery, Yuko Koshimori, Sarah Coakeley, Madeleine Harris, Pablo Rusjan, Jinhee Kim, Sylvain Houle, Antonio P Strafella
BACKGROUND: Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo. METHODS: Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [(18)F]-FEPPA between PD patients and HC...
January 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#12
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
: Triggering Receptor Expressed on Myeloid cells 2 (TREM2), expressed on myeloid cells including microglia in the central nervous system (CNS), has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its trans-membrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease (NHD); however, how AD risk-conferring variants increase AD risk is not clear...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077279/homology-analysis-detects-topological-changes-of-iba1-localization-accompanied-by-microglial-activation
#13
Toshinori Sawano, Ryo Tsuchihashi, Eiichi Morii, Fumiya Watanabe, Kazuaki Nakane, Shinobu Inagaki
The state of microglial activation provides important information about the central nervous system. However, a reliable index of microglial activation in histological samples has yet to be established. Here, we show that microglial activation induces topological changes of Iba1 localization that can be detected by analysis based on homology theory. Analysis of homology was applied to images of Iba1-stained tissue sections, and the 0-dimentional Betti number (b0: the number of solid components) and the 1-dimentional Betti number (b1: the number of windows surrounded by solid components) were obtained...
January 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28064406/up-regulation-of-vps4a-promotes-neuronal-apoptosis-after-intracerebral-hemorrhage-in-adult-rats
#14
Jianbing Ren, Debin Yuan, Lili Xie, Xuelei Tao, Chenwei Duan, Yifeng Bao, Yunfeng He, Jianbin Ge, Hongjian Lu
Vps4, vacuolar protein sorting 4, belongs to ATPases Associated with diverse cellular Activities (AAA) protein family which is made up of Vps4A and Vps4B. Previous studies demonstrated that Vps4A plays vital roles in diverse aspects such as virus budding, the efficient transport of H-Ras to the PM (plasma membrane) and the involvement in the MVB (multivesiculate bodies) pathway. Interestingly, Vps4A is also expressed in the brain. However, the distribution and function of Vps4A in ICH diseases remain unclear...
January 7, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28054940/neuroprotective-effects-of-aged-garlic-extract-on-cognitive-dysfunction-and-neuroinflammation-induced-by-%C3%AE-amyloid-in-rats
#15
Nutchareeporn Nillert, Wanassanun Pannangrong, Jariya Umka Welbat, Wunnee Chaijaroonkhanarak, Kittisak Sripanidkulchai, Bungorn Sripanidkulchai
Neuroinflammation is pathological evidence of Alzheimer's disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects...
January 3, 2017: Nutrients
https://www.readbyqxmd.com/read/28050710/the-copper-bis-thiosemicarbazone-complex-cu-ii-atsm-is-protective-against-cerebral-ischemia-through-modulation-of-the-inflammatory-milieu
#16
Mikko T Huuskonen, Qing-Zhang Tuo, Sanna Loppi, Hiramani Dhungana, Paula Korhonen, Lachlan E McInnes, Paul S Donnelly, Alexandra Grubman, Sara Wojciechowski, Katarina Lejavova, Yuriy Pomeshchik, Laura Periviita, Lotta Kosonen, Martina Giordano, Frederick R Walker, Rong Liu, Ashley I Bush, Jari Koistinaho, Tarja Malm, Anthony R White, Peng Lei, Katja M Kanninen
Developing new therapies for stroke is urgently needed, as this disease is the leading cause of death and disability worldwide, and the existing treatment is only available for a small subset of patients. The interruption of blood flow to the brain during ischemic stroke launches multiple immune responses, characterized by infiltration of peripheral immune cells, the activation of brain microglial cells, and the accumulation of immune mediators. Copper is an essential trace element that is required for many critical processes in the brain...
January 3, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28042008/does-time-heal-all-wounds-experimental-diffuse-traumatic-brain-injury-results-in-persisting-histopathology-in-the-thalamus
#17
Theresa Currier Thomas, Sarah B Ogle, Benjamin M Rumney, Hazel G May, P David Adelson, Jonathan Lifshitz
BACKGROUND: Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors...
December 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/28039536/cardiolipin-in-central-nervous-system-physiology-and-pathology
#18
REVIEW
Caitlin B Pointer, Andis Klegeris
Cardiolipin, an anionic phospholipid found primarily in the inner mitochondrial membrane, has many well-defined roles within the peripheral tissues, including the maintenance of mitochondrial membrane fluidity and the regulation of mitochondrial functions. Within the central nervous system (CNS), cardiolipin is found within both neuronal and non-neuronal glial cells, where it regulates metabolic processes, supports mitochondrial functions, and promotes brain cell viability. Furthermore, cardiolipin has been shown to act as an elimination signal and participate in programmed cell death by apoptosis of both neurons and glia...
December 30, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28039031/worsening-of-memory-deficit-induced-by-energy-dense-diet-in-a-rat-model-of-early-alzheimer-s-disease-is-associated-to-neurotoxic-a%C3%AE-species-and-independent-of-neuroinflammation
#19
Pamela V Martino Adami, Pablo Galeano, Marina L Wallinger, Celia Quijano, Alejandro Rabossi, Eleonora S Pagano, Natividad Olivar, Carlos Reyes Toso, Daniel Cardinali, Luis I Brusco, Sonia Do Carmo, Rafael Radi, Goar Gevorkian, Eduardo M Castaño, A Claudio Cuello, Laura Morelli
Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar...
December 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#20
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
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