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M Samsonia, M Kandelaki, N Baratashvili
Cerebrovascular diseases of ischemic origin still remain the leading cause of death and disability of the population. In acute cerebral discirculation conditions, anaerobic glycolysis is activated, ATP formation rate decreases, the ion pumps work is disrupted and superoxide radicals are formed. Eventually, ionic asymmetry leads to the cytotoxic and vasogenic brain edema. Therefore, it is extremely important to induce simultaneous (complex) effect of medications on the key mechanisms of neuronal damage in process of survival of brain cells during acute ischemic stroke...
May 2018: Georgian Medical News
Bikash Choudhary, Eckhard Mandelkow, Eva-Maria Mandelkow, Ghulam Jeelani Pir
No abstract text is available yet for this article.
June 9, 2018: Neurobiology of Disease
Kandhasamy Sowndhararajan, Ponnuvel Deepa, Minju Kim, Se Jin Park, Songmun Kim
Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the gradual loss of neurons. The development of effective neuroprotective agents to prevent and control neurodegenerative diseases is specifically important. Recently, there has been an increasing interest in selecting flavonoid compounds as potential neuroprotective agents, owing to their high effectiveness with low side effects. Baicalin is one of the important flavonoid compounds, which is mainly isolated from the root of Scutellaria baicalensis Georgi (an important Chinese medicinal herb)...
June 11, 2018: Brain Sciences
Tiege Chen, Yuexiu Dang, Ming Wang, Dongliang Zhang, Yongqiang Guo, Haihong Zhang
Spinal edema is a very important pathophysiological basis for secondary spinal cord injury, which affects the repair and prognosis of spinal cord injury. Aquaporin-4 is widely distributed in various organs of the body, and is highly expressed in the brain and spinal cord. Inward rectifying potassium channel 4.1 is a protein found in astrocytes of central nervous system. It interacts with aquaporins in function. Aquaporin-4 and inward rectifying potassium channel 4.1 play an important role in the formation and elimination of spinal cord edema, inhibition of glial scar formation and promotion of excitotoxic agents exclusion...
May 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Anna E Kirkland, Gabrielle L Sarlo, Kathleen F Holton
Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders...
June 6, 2018: Nutrients
Garth L Maker, Tobias Green, Ian Mullaney, Robert D Trengove
Methamphetamine is an illicit psychostimulant drug that is linked to a number of diseases of the nervous system. The downstream biochemical effects of its primary mechanisms are not well understood, and the objective of this study was to investigate whether untargeted metabolomic analysis of an in vitro model could generate data relevant to what is already known about this drug. Rat B50 neuroblastoma cells were treated with 1 mM methamphetamine for 48 h, and both intracellular and extracellular metabolites were profiled using gas chromatography⁻mass spectrometry...
June 7, 2018: Metabolites
Kyeong-Eun Lee, Young-Sook Kang
OBJECTIVE: Glutamate excitotoxicity provokes neuronal cell damage and death, leading to collapse of the blood-brain barrier (BBB). Recently, it has been reported that l-citrulline, a neutral amino acid and a major precursor of l-arginine in the nitric oxide (NO) cycle, can prevent both neuronal cell death and cerebrovascular cell loss in brain ischemia. Therefore, the objective of this study was to investigate the effect of l-citrulline on glutamate cytotoxicity in the BBB using the conditionally immortalized rat brain capillary endothelial cell line (TR-BBB cells) as an in vitro model of the BBB...
June 2, 2018: Microvascular Research
Roland Patai, Bernát Nógrádi, Valéria Meszlényi, Izabella Obál, József Engelhardt, László Siklós
Amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease is characterized by progressive muscle weakness caused by the degeneration of the motor neurons in the spinal cord and motor cortex. However, according to the recent observations, ALS is a rather complex syndrome which frequently involves symptoms of cognitive impairment. Therefore, ALS cases can be interpreted in a clinico-pathological spectrum spanning from the classical ALS involving only the motor system to the fronto-temporal dementia...
July 30, 2017: Ideggyógyászati Szemle
Natascia Brondino, Matteo Rocchetti, Laura Fusar-Poli, Stefano Damiani, Arianna Goggi, Giuseppe Chiodelli, Serafino Corti, Livia Visai, Pierluigi Politi
OBJECTIVES: Ciliary neurotrophic factor (CNTF) is a neurotrophin which could signal neuronal suffering and at the same time acts as a neuroprotective agent. In the present study we aimed to evaluate CNTF serum levels in Autism Spectrum Disorders (ASD). In fact, considering the role of CNTF as a neuronal damage signal and the role of neuroinflammation, excito-inhibitory imbalance and excitotoxicity in the pathogenesis of ASD, a possible alteration of CNTF in ASD could be hypothesised. METHODS: We recruited 23 individuals with ASD and intellectual disability (ID), 20 ID subjects and 26 typical adults...
June 5, 2018: World Journal of Biological Psychiatry
Mei-Fang Jin, Hong Ni, Li-Li Li
Developmental seizure-induced long-term neuronal hyperexcitation is partially mediated by regenerative mossy fiber sprouting in hippocampus. Yet, there are no effective drugs available to block this pathological process. Recently, leptin has been shown to prevent the sprouting of hippocampal mossy fibers and abnormalities in the neurobehavioral parameters. However, their underlying molecular mechanisms are largely unknown. The purpose of this study was to determine the effect of glutamate on the parameters of zinc homeostasis, mitochondrial functions, and mitophagy regulating factors, as well as to investigate the protective effects of leptin against cytotoxicity of glutamate in murine HT22 hippocampal neuronal cells...
2018: Frontiers in Neurology
Sydney E Doman, Akanksha Girish, Christina L Nemeth, Gabrielle T Drummond, Patrice Carr, Maxine S Garcia, Michael V Johnston, Sujatha Kannan, Ali Fatemi, Jiangyang Zhang, Mary Ann Wilson
Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome...
2018: Frontiers in Neurology
Giuditta Gambino, Mario Allegra, Pierangelo Sardo, Alessandro Attanzio, Luisa Tesoriere, Maria A Livrea, Giuseppe Ferraro, Fabio Carletti
Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer's disease...
2018: Frontiers in Aging Neuroscience
Meng-Ying Liu, Ashley Nemes, Qi-Gang Zhou
Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3' end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs) and neural progenitor cells (NPCs), at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT) can protect newborn neurons from apoptosis and excitotoxicity...
2018: Frontiers in Molecular Neuroscience
Akash K George, Mahavir Singh, Rubens Petit Homme, Avisek Majumder, Harpal S Sandhu, Suresh C Tyagi
Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways...
2018: International Journal of Ophthalmology
Francesca Romana Rizzo, Alessandra Musella, Francesca De Vito, Diego Fresegna, Silvia Bullitta, Valentina Vanni, Livia Guadalupi, Mario Stampanoni Bassi, Fabio Buttari, Georgia Mandolesi, Diego Centonze, Antonietta Gentile
Cytokines are constitutively released in the healthy brain by resident myeloid cells to keep proper synaptic plasticity, either in the form of Hebbian synaptic plasticity or of homeostatic plasticity. However, when cytokines dramatically increase, establishing a status of neuroinflammation, the synaptic action of such molecules remarkably interferes with brain circuits of learning and cognition and contributes to excitotoxicity and neurodegeneration. Among others, interleukin-1 β (IL-1 β ) and tumor necrosis factor (TNF) are the best studied proinflammatory cytokines in both physiological and pathological conditions and have been invariably associated with long-term potentiation (LTP) (Hebbian synaptic plasticity) and synaptic scaling (homeostatic plasticity), respectively...
2018: Neural Plasticity
Maja Jazvinšćak Jembrek, Vedrana Radovanović, Josipa Vlainić, Lidija Vuković, Nikolina Hanžić
Excitotoxicity is a pathological process in which neuronal dysfunction and death are induced by excessive glutamate stimulation, the major fast excitatory neurotransmitter in the mammalian brain. Excitotoxicity-induced neurodegeneration is a contributing factor in ischemia-induced brain damage, traumatic brain injury, and various neurodegenerative diseases. It is triggered by calcium overload due to prolonged over-activation of ionotropic N-methyl-D-aspartate (NMDA) receptors. Enhanced Ca2+ release results in neuronal vulnerability through several intertwined mechanisms, including activation of proteolytic enzymes, increased production of reactive oxygen species (ROS), mitochondrial dysfunction and modulation of intracellular signalling pathways...
May 30, 2018: Toxicology
Ana Ledo, Rui M Barbosa, João Laranjinha
Nitric oxide (• NO) is an ubiquitous signaling molecule that participates in molecular processes associated with several neural phenomena ranging from memory formation to excitotoxicity. In the hippocampus, neuronal • NO production is coupled to the activation of NMDA type glutamate receptors. Cytochrome c oxidase has emerged as a novel target for • NO, which competes with O2 for binding to this mitochondrial complex. This reaction establishes • NO as a regulator of cellular metabolism and, possibly, mitochondrial production of reactive oxygen species which participate in cellular signaling...
2018: Methods in Molecular Biology
Perrine Inquimbert, Martin Moll, Alban Latremoliere, Chi-Kun Tong, John Whang, Gregory F Sheehan, Brendan M Smith, Erica Korb, Maria C P Athié, Olusegun Babaniyi, Nader Ghasemlou, Yuchio Yanagawa, C David Allis, Patrick R Hof, Joachim Scholz
Peripheral nerve lesions provoke apoptosis in the dorsal horn of the spinal cord. The cause of cell death, the involvement of neurons, and the relevance for the processing of somatosensory information are controversial. Here, we demonstrate in a mouse model of sciatic nerve injury that glutamate-induced neurodegeneration and loss of γ-aminobutyric acid (GABA)ergic interneurons in the superficial dorsal horn promote the transition from acute to chronic neuropathic pain. Conditional deletion of Grin1, the essential subunit of N-methyl-d-aspartate-type glutamate receptors (NMDARs), protects dorsal horn neurons from excitotoxicity and preserves GABAergic inhibition...
May 29, 2018: Cell Reports
Cinzia Mallozzi, Mariacristina Parravano, Lucia Gaddini, Marika Villa, Flavia Pricci, Fiorella Malchiodi-Albedi, Andrea Matteucci
Curcumin is one of the major compounds contained in turmeric, the powdered rhizome of Curcuma longa. Results obtained in various experimental models indicate that curcumin has the potential to treat a large variety of neuronal diseases. Excitotoxicity, the toxicity due to pathological glutamate receptors stimulation, has been considered to be involved in several ocular pathologies including ischemia, glaucoma, and diabetic retinopathy. The NMDA receptor (NMDAR), a heteromeric ligand-gated ion channel, is composed of GluN1 and GluN2 subunits...
May 30, 2018: Cellular and Molecular Neurobiology
Sajad Mir, Douglas A Andres
PURPOSE: Ras-like without CAAX 1 (RIT1/Rit) is a member of the Ras subfamily of small GTP-binding proteins with documented roles in regulating neuronal function, including contributions to neurotrophin signaling, neuronal survival and neurogenesis. The aim of the study was to (1) examine the expression of RIT1 protein in mouse retina and retinal cell types and (2) determine whether RIT1 contributes to retinal ganglion cell survival and synaptic stability following excitotoxic stress. MATERIALS AND METHODS: Gene expression and immunohistochemical analysis were used to examine RIT1 expression in the mouse retina...
May 29, 2018: Current Eye Research
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