Sample records for excitotoxicity inflicts paranodal

  1. Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction. (United States)

    Fu, Yan; Sun, Wenjing; Shi, Yunzhou; Shi, Riyi; Cheng, Ji-Xin


    Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation.

  2. Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction.

    Directory of Open Access Journals (Sweden)

    Yan Fu


    Full Text Available Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation.

  3. Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.

    Directory of Open Access Journals (Sweden)

    Charles F Babbs

    Full Text Available This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity.

  4. Pregabalin attenuates excitotoxicity in diabetes.

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    Chin-Wei Huang

    Full Text Available Diabetes can exacerbate seizures and worsen seizure-related brain damage. In the present study, we aimed to determine whether the standard antiepileptic drug pregabalin (PGB protects against pilocarpine-induced seizures and excitotoxicity in diabetes. Adult male Sprague-Dawley rats were divided into either a streptozotocin (STZ-induced diabetes group or a normal saline (NS group. Both groups were further divided into subgroups that were treated intravenously with either PGB (15 mg/kg or a vehicle; all groups were treated with subcutaneous pilocarpine (60 mg/kg to induce seizures. To evaluate spontaneous recurrent seizures (SRS, PGB-pretreated rats were fed rat chow containing oral PGB (450 mg for 28 consecutive days; vehicle-pretreated rats were fed regular chow. SRS frequency was monitored for 2 weeks from post-status epilepticus day 15. We evaluated both acute neuronal loss and chronic mossy fiber sprouting in the CA3 area. In addition, we performed patch clamp recordings to study evoked excitatory postsynaptic currents (eEPSCs in hippocampal CA1 neurons for both vehicle-treated rats with SRS. Finally, we used an RNA interference knockdown method for Kir6.2 in a hippocampal cell line to evaluate PGB's effects in the presence of high-dose ATP. We found that compared to vehicle-treated rats, PGB-treated rats showed less severe acute seizure activity, reduced acute neuronal loss, and chronic mossy fiber sprouting. In the vehicle-treated STZ rats, eEPSC amplitude was significantly lower after PGB administration, but glibenclamide reversed this effect. The RNA interference study confirmed that PGB could counteract the ATP-sensitive potassium channel (KATP-closing effect of high-dose ATP. By opening KATP, PGB protects against neuronal excitotoxicity, and is therefore a potential antiepileptogenic in diabetes. These findings might help develop a clinical algorithm for treating patients with epilepsy and comorbid metabolic disorders.

  5. White shark ( Carcharodon carcharias )-inflicted bite wounds ...

    African Journals Online (AJOL)

    White shark ( Carcharodon carcharias )-inflicted bite wounds observed on Cape fur seals ( Arctocephalus pusillus pusillus ) at Black Rocks, Algoa Bay, South Africa. ... The low number of bite-inflicted injuries observed suggests that white sharks attack seals infrequently at Black Rocks. Key words: Algoa Bay, bite injuries, ...

  6. Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy (United States)

    Fu, Yan; Frederick, Terra J.; Huff, Terry B.; Goings, Gwendolyn E.; Miller, Stephen D.; Cheng, Ji-Xin


    How demyelination is initiated is a standing question for pathology of multiple sclerosis. By label-free coherent anti-Stokes Raman scattering (CARS) imaging of myelin lipids, we investigate myelin integrity in the lumbar spinal cord tissue isolated from naïve SJL mice, and from mice at the onset, peak acute, and remission stages of relapsing experimental autoimmune encephalomyelitis (EAE). Progressive demyelinating disease is initially characterized by the retraction of paranodal myelin both at the onset of disease and at the borders of acute demyelinating lesions. Myelin retraction is confirmed by elongated distribution of neurofascin proteins visualized by immunofluorescence. The disruption of paranodal myelin subsequently exposes Kv1.2 channels at the juxtaparanodes and lead to the displacement of Kv1.2 channels to the paranodal and nodal domains. Paranodal myelin is partially restored during disease remission, indicating spontaneous myelin regeneration. These findings suggest that paranodal domain injury precedes formation of internodal demyelinating lesions in relapsing EAE. Our results also demonstrate that CARS microscopy is an effective readout of myelin disease burden.

  7. Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment.

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    Charis R Szymanski

    Full Text Available Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

  8. Self-inflicted burns: a case series. (United States)

    Henderson, Antony; Wijewardena, Aruna; Streimer, Jeff; Vandervord, John


    Self-inflicted burns are regularly admitted to burns units worldwide. Most of these patients are referred to psychiatric services and are successfully treated however some return to hospital with recurrent self-inflicted burns. The aim of this study is to explore the characteristics of the recurrent self-inflicted burn patients admitted to the Royal North Shore Hospital during 2004-2011. Burn patients were drawn from a computerized database and recurrent self-inflicted burn patients were identified. Of the total of 1442 burn patients, 40 (2.8%) were identified as self-inflicted burns. Of these patients, 5 (0.4%) were identified to have sustained previous self-inflicted burns and were interviewed by a psychiatrist. Each patient had been diagnosed with a borderline personality disorder and had suffered other forms of deliberate self-harm. Self-inflicted burns were utilized to relieve or help regulate psychological distress, rather than to commit suicide. Most patients had a history of emotional neglect, physical and/or sexual abuse during their early life experience. Following discharge from hospital, the patients described varying levels of psychiatric follow-up, from a post-discharge review at a local community mental health centre to twice-weekly psychotherapy. The patients who engaged in regular psychotherapy described feeling more in control of their emotions and reported having a longer period of abstinence from self-inflicted burn. Although these patients represent a small proportion of all burns, the repeat nature of their injuries led to a significant use of clinical resources. A coordinated and consistent treatment pathway involving surgical and psychiatric services for recurrent self-inflicted burns may assist in the management of these challenging patients. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  9. Protective effect of parvalbumin on excitotoxic motor neuron death

    DEFF Research Database (Denmark)

    Van den Bosch, L.; Schwaller, B.; Vleminckx, V.


    Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin......Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin...

  10. Myelin Organization in the Nodal, Paranodal, and Juxtaparanodal Regions Revealed by Scanning X-Ray Microdiffraction (United States)

    Makowski, Lee; Palmisano, Marilena; Burghammer, Manfred; Riekel, Christian; Kirschner, Daniel A.


    X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198–202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205–208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein). Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular) to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS. PMID:24984037

  11. Self-inflicted lesions in dermatology

    DEFF Research Database (Denmark)

    Gieler, Uwe; Consoli, Sylvie G; Tomás-Aragones, Lucía


    at clarifying the terminology related to these disorders. A flow chart and glossary of terms and definitions are presented to facilitate the classification and management of self-inflicted skin lesions. Several terms are critically discussed, including: malingering; factitious disorders; Münchausen's syndrome...

  12. Self-inflicted serious injuries among adolescents in Zambia | Muula ...

    African Journals Online (AJOL)

    The following variables were associated with history of self inflicted injury: worry; sadness; suicidal behavior; history of ever having been drunk and marijuana use. Reported history of injury and self-inflicted injury among in-school adolescents in Zambia are common. History of self-inflicted injury was associated with other ...

  13. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

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    Terry B Huff


    Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  14. Pain insensitivity syndrome misinterpreted as inflicted burns. (United States)

    van den Bosch, Gerbrich E; Baartmans, Martin G A; Vos, Paul; Dokter, Jan; White, Tonya; Tibboel, Dick


    We present a case study of a 10-year-old child with severe burns that were misinterpreted as inflicted burns. Because of multiple injuries since early life, the family was under suspicion of child abuse and therefore under supervision of the Child Care Board for 2 years before the boy was burned. Because the boy incurred the burns without feeling pain, we conducted a thorough medical examination and laboratory testing, evaluated detection and pain thresholds, and used MRI to study brain morphology and brain activation patterns during pain between this patient and 3 healthy age- and gender-matched controls. We found elevated detection and pain thresholds and lower brain activation during pain in the patient compared with the healthy controls and reference values. The patient received the diagnosis of hereditary sensory and autonomic neuropathy type IV on the basis of clinical findings and the laboratory testing, complemented with the altered pain and detection thresholds and MRI findings. Hereditary sensory and autonomic neuropathy IV is a very rare congenital pain insensitivity syndrome characterized by the absence of pain and temperature sensation combined with oral mutilation due to unawareness, fractures, and anhidrosis caused by abnormalities in the peripheral nerves. Health care workers should be aware of the potential presence of this disease to prevent false accusations of child abuse. Copyright © 2014 by the American Academy of Pediatrics.

  15. Glutamate-mediated excitotoxicity in schizophrenia: a review. (United States)

    Plitman, Eric; Nakajima, Shinichiro; de la Fuente-Sandoval, Camilo; Gerretsen, Philip; Chakravarty, M Mallar; Kobylianskii, Jane; Chung, Jun Ku; Caravaggio, Fernando; Iwata, Yusuke; Remington, Gary; Graff-Guerrero, Ariel


    Findings from neuroimaging studies in patients with schizophrenia suggest widespread structural changes although the mechanisms through which these changes occur are currently unknown. Glutamatergic activity appears to be increased in the early phases of schizophrenia and may contribute to these structural alterations through an excitotoxic effect. The primary aim of this review was to describe the possible role of glutamate-mediated excitotoxicity in explaining the presence of neuroanatomical changes within schizophrenia. A Medline(®) literature search was conducted, identifying English language studies on the topic of glutamate-mediated excitotoxicity in schizophrenia, using the terms "schizophreni" and "glutam" and (("MRS" or "MRI" or "magnetic resonance") or ("computed tomography" or "CT")). Studies concomitantly investigating glutamatergic activity and brain structure in patients with schizophrenia were included. Results are discussed in the context of findings from preclinical studies. Seven studies were identified that met the inclusion criteria. These studies provide inconclusive support for the role of glutamate-mediated excitotoxicity in the occurrence of structural changes within schizophrenia, with the caveat that there is a paucity of human studies investigating this topic. Preclinical data suggest that an excitotoxic effect may occur as a result of a paradoxical increase in glutamatergic activity following N-methyl-D-aspartate receptor hypofunction. Based on animal literature, glutamate-mediated excitotoxicity may account for certain structural changes present in schizophrenia, but additional human studies are required to substantiate these findings. Future studies should adopt a longitudinal design and employ magnetic resonance imaging techniques to investigate whether an association between glutamatergic activity and structural changes exists in patients with schizophrenia. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  16. Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death

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    Rojas Monica A


    Full Text Available Abstract Background We previously found that cyclooxygenase 2 (COX-2 was expressed in dying oligodendrocytes at the onset of demyelination in the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD model of multiple sclerosis (MS (Carlson et al. J.Neuroimmunology 2006, 149:40. This suggests that COX-2 may contribute to death of oligodendrocytes. Objective The goal of this study was to examine whether COX-2 contributes to excitotoxic death of oligodendrocytes and potentially contributes to demyelination. Methods The potential link between COX-2 and oligodendrocyte death was approached using histopathology of MS lesions to examine whether COX-2 was expressed in dying oligodendrocytes. COX-2 inhibitors were examined for their ability to limit demyelination in the TMEV-IDD model of MS and to limit excitotoxic death of oligodendrocytes in vitro. Genetic manipulation of COX-2 expression was used to determine whether COX-2 contributes to excitotoxic death of oligodendrocytes. A transgenic mouse line was generated that overexpressed COX-2 in oligodendrocytes. Oligodendrocyte cultures derived from these transgenic mice were used to examine whether increased expression of COX-2 enhanced the vulnerability of oligodendrocytes to excitotoxic death. Oligodendrocytes derived from COX-2 knockout mice were evaluated to determine if decreased COX-2 expression promotes a greater resistance to excitotoxic death. Results COX-2 was expressed in dying oligodendrocytes in MS lesions. COX-2 inhibitors limited demyelination in the TMEV-IDD model of MS and protected oligodendrocytes against excitotoxic death in vitro. COX-2 expression was increased in wild-type oligodendrocytes following treatment with Kainic acid (KA. Overexpression of COX-2 in oligodendrocytes increased the sensitivity of oligodendrocytes to KA-induced excitotoxic death eight-fold compared to wild-type. Conversely, oligodendrocytes prepared from COX-2 knockout mice showed a

  17. Motor and sensory neuropathy due to myelin infolding and paranodal damage in a transgenic mouse model of Charcot–Marie–Tooth disease type 1C (United States)

    Lee, Samuel M.; Sha, Di; Mohammed, Anum A.; Asress, Seneshaw; Glass, Jonathan D.; Chin, Lih-Shen; Li, Lian


    Charcot–Marie–Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt–Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients. PMID:23359569

  18. Self-inflicted trans-oral intracranial stab wound. (United States)

    Kim, Seong Woo; Kim, Jong Hun; Han, Zee-A


    Intracranial stab wounds are low-velocity, penetrating injuries to the brain and fatality and outcome significantly depend on route, depth and location of cranial penetration. Due to the effective barrier provided by the adult calvarium, most injuries occur through the orbitae or temporal regions where bony layers are thin. Self-inflicted intracranial stab wounds are an even rarer form of traumatic brain injury, with common entry points being the orbital space and the nose. Intracranial brainstem injuries mostly result in death, with reported penetration areas being the pons or midbrain. The following report reviews a first reported case of self-inflicted intracranial stabbing via a trans-oral route with lesions to the medulla oblongata and cerebellum. Unlike previous cases of low velocity penetrating injuries to the brainstem, the patient underwent full neurologic recovery after manual knife removal and intensive rehabilitation. Self-inflicted transcranial injuries have been mentioned only briefly and sporadically in the literature. This article highlights a rare case of self-inflicted intracranial stabbing with a not yet reported entry route and brainstem lesion. Unlike the other fatal outcomes associated with such injuries, the patient underwent full neurological and functional recovery through a comprehensive approach that included intensive rehabilitation.

  19. The Crisis in the Humanities: A Self-Inflicted Wound? (United States)

    Kalin, Mike


    While the allure of Silicon Valley undoubtedly attracts students, the declining interest in the humanities at both the secondary and postsecondary levels is primarily a self-inflicted wound. Many educators often employ teaching methods that alienate students and make them feel as though the only reason for reading literature or studying history is…

  20. Epidemiology and financial implications of self-inflicted burns. (United States)

    George, S; Javed, M; Hemington-Gorse, S; Wilson-Jones, N


    The cost of the treatment of burns is high especially in self-inflicted burns with prolonged treatment. We performed a retrospective review of the self-inflicted burns at our regional burns centre to determine the costs incurred in their management and to identify factors which could reduce the financial burden in the future. The data was collected retrospectively of all the inpatient and outpatient self-inflicted burns presenting to our regional burns centre in the year 2011. Twenty one patients (out of a total of 870 patients) presented with self-inflicted burns to our centre in 2011. Five (23.8%) were major burns with an average of 53.2% Total Body Surface Area (TBSA) and 16 (76.2%) were minor burns with an average of 0.5% TBSA. 11 (52.4%) patients had flame burns including 4 self-immolation burns. The mortality rate was 4.8% (n=1). Five (23.8%) patients underwent surgical treatment. Seven (33.3%) patients were treated in intensive care and with average stay of 46.85 days. Critical care and theatre attendances made up most of the costs with average ICU stay per patient calculated at £313,131/day. The total cost of all 21 patients was £1,581,856. Burns are preventable injuries, early detection and intervention in patients with propensity to self-inflict burns can possibly reduce the costs of treatment in the future. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  1. HIP/PAP prevents excitotoxic neuronal death and promotes plasticity


    Haldipur, Parthiv; Dupuis, Nina; Degos, Vincent; Moniaux, Nicolas; Chhor, Vibol; Rasika, Sowmyalakshmi; Schwendimann, Leslie; Le Charpentier, Tifenn; Rougier, Elodie; Amouyal, Paul; Amouyal, Gilles; Dournaud, Pascal; Bréchot, Christian; El Ghouzzi, Vincent; Faivre, Jamila


    Objectives Excitotoxicity plays a significant role in the pathogenesis of perinatal brain injuries. Among the consequences of excessive activation of the N-methyl-d-aspartate (NMDA)-type glutamate are oxidative stress caused by free radical release from damaged mitochondria, neuronal death and subsequent loss of connectivity. Drugs that could protect nervous tissue and support regeneration are attractive therapeutic options. The hepatocarcinoma intestine pancreas protein/pancreatitis-associat...

  2. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

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    Vinet Jonathan


    Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

  3. Penetrating anterior skull base fracture inflicted by a cow's horn


    Adomas Bunevicius; Karolis Bareikis; Laimutis Kalasauskas; Arimantas Tamasauskas


    Farm workers are at increased risk for animal-inflicted head injuries that are associated with significant morbidity and occasionally may be fatal. These injuries may cause permanent eye damage with or without concomitant skull base fracture. Here, we present a male farmer who suffered a cow attack that resulted in perforating orbital injury with comminuted frontobasal cranial fracture caused by a cow's horn. The next day, the patient developed nasal and orbital cerebrospinal fluid (CSF) leak...

  4. [Self-inflicted laser-induced maculopathy in adolescence]. (United States)

    Hohberger, B; Bergua, A


    Reports of laser-induced ocular injuries have become more frequent in recent years, especially due to high-energy laser pointers. The article presents for the first time in the German literature a case of self-inflicted laser-induced maculopathy in an adolescent. In addition to the clinical findings, the results of funduscopy and spectral domain optical coherence tomography (SD-OCT) follow-up are presented.

  5. HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins. (United States)

    Brügger, Valérie; Engler, Stefanie; Pereira, Jorge A; Ruff, Sophie; Horn, Michael; Welzl, Hans; Münger, Emmanuelle; Vaquié, Adrien; Sidiropoulos, Páris N M; Egger, Boris; Yotovski, Peter; Filgueira, Luis; Somandin, Christian; Lühmann, Tessa C; D'Antonio, Maurizio; Yamaguchi, Teppei; Matthias, Patrick; Suter, Ueli; Jacob, Claire


    The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC)-axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc)155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease.

  6. Mitochondrial impairment induces excitotoxic death in cerebellar granule cells. (United States)

    Bobba, Antonella; Atlante, Anna; Azzariti, Amalia; Sgaramella, Giuseppe; Calissano, Pietro; Marra, Ersilia


    A close relationship links mitochondria to cell death with mitochondrial function-impairment considered a major biochemical event in the process of both apoptosis and necrosis. We have used different inhibitors of oxidative phosphorylation, i.e. mitochondrial respiratory chain and ATP synthesis inhibitors, and an uncoupler to investigate the mode of cell death caused by these compounds in cerebellar granule cells. This study shows that in cultured cerebellar granule cells either oxidative phosphorylation inhibitors or uncoupler induce an excitotoxic-like reaction which is mediated by activation of NMDA receptors and is likely due to the release of glutamate. Consistently, survival may occur if the toxic action of glutamate is prevented.

  7. Bilateral circumferential macular folds in inflicted childhood neurotrauma. (United States)

    Airiani, Suzanna; Fine, Howard F; Walrath, Joseph D; Chiang, Michael F; Flynn, John T


    To report an infant with inflicted neurotrauma who exhibited bilateral circumferential macular folds. Bedside ophthalmic examination and fundus photography using RetCam-II (Clarity Medical Systems, Pleasanton, CA). Both pupils were miotic and nonreactive. External and anterior segments showed no abnormality. The fundus showed bilateral diffuse multilaminar retinal, subhyaloid, and vitreous hemorrhages. Distinctive macular folds were noted bilaterally. Circumferential macular folds are most commonly found in abused infants, although it has been suggested that they may be associated with Terson syndrome and severe crush injury.

  8. Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

    NARCIS (Netherlands)

    Harkany, Tibor; Varga, Csaba; Grosche, Jens; Mulder, Jan; Luiten, Paul G.M.; Hortobágyi, Tibor; Penke, Botond; Härtig, Wolfgang


    Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP

  9. Penetrating anterior skull base fracture inflicted by a cow's horn

    Directory of Open Access Journals (Sweden)

    Adomas Bunevicius


    Full Text Available Farm workers are at increased risk for animal-inflicted head injuries that are associated with significant morbidity and occasionally may be fatal. These injuries may cause permanent eye damage with or without concomitant skull base fracture. Here, we present a male farmer who suffered a cow attack that resulted in perforating orbital injury with comminuted frontobasal cranial fracture caused by a cow's horn. The next day, the patient developed nasal and orbital cerebrospinal fluid (CSF leak. Computed Tomography cisternography revealed CSF leakage to frontal and maxillary sinuses. The patient was treated using prophylactic antibiotic therapy, lumbar drainage, and underwent craniotomy for debridement and dural tear plastic. Post operative course was uneventful and there were no signs of CSF leak 1 year after the surgery. The case illustrates unusual injury inflicted by a cow's horn and underscores the importance of careful investigation for underlying skull base fracture and CSF leakage in patients sustaining perforating orbital injuries. Adequate and timely management of dural tears is associated with favorable outcomes.

  10. Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers. (United States)

    Piao, Hua; Minohara, Motozumi; Kawamura, Nobutoshi; Li, Wei; Mizunoe, Yoshimitsu; Umehara, Fujio; Goto, Yoshinobu; Kusunoki, Susumu; Matsushita, Takuya; Ikenaka, Kazuhiro; Maejima, Takashi; Nabekura, Jun-ichi; Yamasaki, Ryo; Kira, Jun-ichi


    In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na(+) currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of

  11. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi


    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  12. BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB (United States)

    Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)


    The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.

  13. Cellular prion protein and NMDA receptor modulation: protecting against excitotoxicity

    Directory of Open Access Journals (Sweden)

    Stefanie A.G. Black


    Full Text Available Although it is well established that misfolding of the cellular prion protein (PrPC into the beta-sheet-rich, aggregated scrapie conformation (PrPSc causes a variety of transmissible spongiform encephalopathies (TSEs, the physiological roles of PrPC are still incompletely understood. There is accumulating evidence describing the roles of PrPC in neurodegeneration and neuroinflammation. Recently, we identified a functional regulation of NMDA receptors by PrPC that involves formation of a physical protein complex between these proteins. Excessive NMDA receptor activity during conditions such as ischemia mediates enhanced Ca2+ entry into cells and contributes to excitotoxic neuronal death. In addition, NMDA receptors and/or PrPC play critical roles in neuroinflammation and glial cell toxicity. Inhibition of NMDA receptor activity protects against PrPSc-induced neuronal death. Moreover, in mice lacking PrPC, infarct size is increased after focal cerebral ischemia, and absence of PrPC increases susceptibility of neurons to NMDA receptor-dependent death. Recently, PrPC was found to be a receptor for oligomeric beta-amyloid (Abeta peptides, suggesting a role for PrPC in Alzheimer’s disease. Our recent findings suggest that Abeta peptides enhance NMDA receptor current by perturbing the normal copper- and PrPC-dependent regulation of these receptors. Here, we review evidence highlighting a role for PrPC in preventing NMDA receptor-mediated excitotoxicity and inflammation. There is a need for more detailed molecular characterization of PrPC-mediated regulation of NMDA receptors, such as determining which NMDA receptor subunits mediate pathogenic effects upon loss of PrPC-mediated regulation and identifying PrPC binding site(s on the receptor. This knowledge will allow development of novel therapeutic interventions for not only TSEs, but also for Alzheimer’s disease and other neurodegenerative disorders involving dysfunction of PrPC.

  14. Monosodium glutamate neonatal treatment as a seizure and excitotoxic model. (United States)

    López-Pérez, Silvia Josefina; Ureña-Guerrero, Mónica Elisa; Morales-Villagrán, Alberto


    Monosodium glutamate (MSG) subcutaneously administrated to neonatal rats induces several neurochemical alterations in the brain, which have been associated with an excitotoxic process triggered by an over activation of glutamate receptors; however there are few systematic studies about initial changes in intracerebroventricular (i.c.v.) Glu levels produced by MSG in the brain. Thus, to characterize these changes, rat pups were injected with a MSG solution at 1, 3, 5 and 7 postnatal days (PD), and i.c.v. Glu levels and hippocampal total content of related amino acids (Asp, Glu, Gln, Gly, Tau, Ala and GABA) were estimated before, immediately and after each injection. Behavioral and EEG responses were also monitored after MSG administrations. Significant rise in i.c.v. Glu levels were found, mainly in response to the first and second injection. Moreover, the total content of all amino acids evaluated also increased during the first hour after the first MSG administration but only Glu and GABA remained elevated after 24 h. These biochemical modifications were accompanied with behavioral alterations characterized by: screeching, tail stiffness, head nodding, emprosthotonic flexion episodes and generalized tonic-clonic convulsions, which were associated with electroencephalographic pattern alterations. Altered behavior found in animals treated with MSG suggests an initial seizure situation. Although four MSG administrations were used, the most relevant findings were observed after the first and second administrations at PD1 and PD3, suggesting that only two MSG injections could be sufficient to resemble a seizure and/or excitotoxic model. 2009 Elsevier B.V. All rights reserved.

  15. Bear-inflicted injuries - a report from Nepal. (United States)

    Atreya, Alok; Kanchan, Tanuj; Nepal, Samata; Acharya, Jenash


    Upper Mustang in the Northern Himalayan range of Nepal is the home of brown bears (Ursusarctos). Low-plant biomass as a result of scanty rainfall in Upper Mustang is a reason for habitat overlap of humans and wild animals. Humans who enter into the wild to collect firewood and graze cattle are liable to wild animal attacks. Such attacks, especially by brown bears, are readily identified by the type of injuries. These are more commonly confined to head and neck regions. Cutting, gnawing and tearing by sharp teeth and claws produces specific pattern of injuries, which are devastating but seldom fatal. This article reports a rare case of brown bear injury inflicted upon a man from the Upper Mustang region in Nepal. © The Author(s) 2016.

  16. Apoptosis and necrosis occurring in excitotoxic cell death in isolated chick embryo retina

    National Research Council Canada - National Science Library

    Ientile, Riccardo; Macaione, Vincenzo; Teletta, Maria; Pedale, Santa; Torre, Valerio; Macaione, Salvatore


    Excitotoxic studies using isolated chick embryo retina indicated that such an in vitro model provides a valid tool to characterize the effect of different agonists for subtypes of glutamate ionotropic receptors...

  17. An unusual case of extensive self-inflicted cement burn. (United States)

    Catalano, F; Mariano, F; Maina, G; Bianco, C; Nuzzo, J; Stella, M


    Cement is a fine powder used to bind sand and stones into a matrix of concrete, making up the world's most frequently used building material in the construction industry. First described by Ramazzini in his book "De Morbis Artificia Diatriba" in 1700, the effect of cement on the skin was presumed to be due to contact dermatitis. The first cement burns case was published by Rowe and Williams in 1963. Cement handling has been found to be responsible for many cases of occupational burns (generally full-thickness) usually affecting a limited TBSA, rarely greater than 5%, with localization especially in the lower limbs. We describe an unusual case of a self-inflicted cement burn involving 75% TBSA. A 28-yr-old building worker attempted suicide by jumping into a cement mixer in a truck. Upon arrival at our burn centre, clinical examination revealed extensive burn (75% TBSA - 40% full-thickness) involving face, back, abdomen, upper limbs and circumferentially lower limbs, sparing the hands and feet. The patient was sedated, mechanically ventilated, and subjected to escharotomy of the lower limbs in the emergency room. The following day, the deep burns in the lower limbs were excised down to the fascia and covered with meshed allografts. Owing to probable intestinal and skin absorption of cement, metal toxicity was suspected and dialysis and forced diuresis were therefore initiated on day 3. The patient's clinical conditions gradually worsened and he died on day 13 from the multi-organ failure syndrome.

  18. Kidins220/ARMS downregulation by excitotoxic activation of NMDARs reveals its involvement in neuronal survival and death pathways

    National Research Council Canada - National Science Library

    López-Menéndez, Celia; Gascón, Sergio; Sobrado, Mónica; Vidaurre, Oscar G; Higuero, Alonso M; Rodríguez-Peña, Angeles; Iglesias, Teresa; Díaz-Guerra, Margarita


    .... Here, we identify an association between these proteins and discover that excitotoxicity, a specific form of neuronal death induced by NMDAR overstimulation, dramatically decreases Kidins220/ARMS...

  19. MRI Overestimates Excitotoxic Amygdala Lesion Damage in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Benjamin M. Basile


    Full Text Available Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately. Previous research has shown that in vivo T2-weighted magnetic resonance imaging (MRI accurately estimates damage following selective ibotenic acid lesions of the hippocampus. Here, we show that the same does not apply to lesions of the amygdala. Across 19 hemispheres from 13 rhesus monkeys, MRI assessment consistently overestimated amygdala damage as assessed by microscopic examination of Nissl-stained histological material. Two outliers suggested a linear relation for lower damage levels, and values of unintended amygdala damage from a previous study fell directly on that regression line, demonstrating that T2 hypersignal accurately predicts damage levels below 50%. For unintended damage, MRI estimates correlated with histological assessment for entorhinal cortex, perirhinal cortex and hippocampus, though MRI significantly overestimated the extent of that damage in all structures. Nevertheless, ibotenic acid injections routinely produced extensive intentional amygdala damage with minimal unintended damage to surrounding structures, validating the general success of the technique. The field will benefit from more research into in vivo lesion assessment techniques, and additional evaluation of the accuracy of MRI assessment in different brain areas. For now, in vivo MRI assessment of ibotenic acid lesions of the amygdala can be used to confirm successful injections, but MRI estimates of lesion extent should be interpreted with caution.

  20. Self-Inflicted Orbito-Cranial Injury Secondary to Gunshot: Case Report

    Directory of Open Access Journals (Sweden)

    Yam Bahadur Roka


    Full Text Available The eye may be injured by various penetrating and non-penetrating injuries like sticks, pencils, rods, gunshot and chopsticks. Self-inflicted gunshot injuries have been rarely reported in literature. This case is interesting in multiple aspects which include poverty, lack of education and the failure of government to ensure control of the use of firearms in Nepal. We report a case of self-inflicted gun injury which was managed successfully.

  1. Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity. (United States)

    Schuettauf, Frank; Vorwerk, Christian; Naskar, Rita; Orlin, Anton; Quinto, Kristine; Zurakowski, David; Dejneka, Nadine S; Klein, Ronald L; Meyer, Edward M; Bennett, Jean


    Brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) hold much promise for the protection of retinal ganglion cells against excitotoxic cell death. We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated viral (AAV) vector and tested their efficacy in two models of excitotoxicity. Rat retinas were infected with AAV vectors encoding bFGF or BDNF. A control vector containing green fluorescent protein (GFP) was injected in the contralateral eye. Eyes were subjected to either an intravitreal injection of N-methyl-D-aspartate (NMDA) or optic nerve crush, and ganglion cell survival was evaluated. AAV.CMV.bFGF and AAV.CBA.BDNF were neuroprotective against NMDA injection 1 month post-treatment. Additionally, AAV.CMV.bFGF was protective against optic nerve crush. AAV-mediated delivery of bFGF and BDNF can promote retinal cell survival following excitotoxic insult.

  2. [Alleged assault in a forest: An unusual case of self-inflicted blunt injury]. (United States)

    Kunz, Sebastian Niko; Tutsch-Bauer, Edith


    The medico-legal assessment of potentially self-inflicted injuries is an important field of clinical forensic medicine. Compared with sharp force injuries, it is much more difficult to distinguish blunt injuries caused by another party from self-inflicted lesions. We present a case of a young female doctor, who was allegedly attacked by an unknown stranger during her evening walk in the woods. She claimed to have been hit repeatedly on the head and arms with a stone. During the forensic investigation, blunt injuries could be confirmed on her head and forearms. Based on the arrangement and intensity of the injuries, together with the result of a bloodstain pattern analysis of the weapon, the victim's statement could be disproved. After being confronted with the results of the investigation, the woman admitted to have inflicted the injuries herself. This case is an unusual and rare example of self-inflicted blunt injury. It shows that the criteria of self-inflicted injuries can also be applied to blunt trauma. However, due to the small number of cases, a high degree of caution is required from the forensic expert.

  3. Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions (United States)

    Le Prell, Colleen G.; Yagi, Masao; Kawamoto, Kohei; Beyer, Lisa A.; Atkin, Graham; Raphael, Yehoash; Dolan, David F.; Bledsoe, Sanford C.; Moody, David B.


    Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration. As observed following acute excitotoxic insult, complete functional recovery was evident within 7 days of discontinuing the AMPA infusion. Distortion product otoacoustic emissions were not affected by chronic AMPA infusion, suggesting that trauma to outer hair cells did not contribute to AMPA-induced deficits in acoustic sensitivity. Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals.

  4. Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration. (United States)

    Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles; Duplus, Eric


    NAD + depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD + was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD + to NR prompted us to probe the effects of NAD + and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD + reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD + Moreover, the stronger effect of NR compared to NAD + depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD + and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD + in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD + homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B 3 , protects against excitotoxicity-induced axonal degeneration. © FASEB.

  5. Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus. (United States)

    Martínez-Moreno, M; Batlle, M; Ortega, F J; Gimeno-Bayón, J; Andrade, C; Mahy, N; Rodríguez, M J


    Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function. (United States)

    Gudiño-Cabrera, Graciela; Ureña-Guerrero, Monica E; Rivera-Cervantes, Martha C; Feria-Velasco, Alfredo I; Beas-Zárate, Carlos


    It is likely that monosodium glutamate (MSG) is the excitotoxin that has been most commonly employed to characterize the process of excitotoxicity and to improve understanding of the ways that this process is related to several pathological conditions of the central nervous system. Excitotoxicity triggered by neonatal MSG treatment produces a significant pathophysiological impact on adulthood, which could be due to modifications in the blood-brain barrier (BBB) permeability and vice versa. This mini-review analyzes this topic through brief descriptions about excitotoxicity, BBB structure and function, role of the BBB in the regulation of Glu extracellular levels, conditions that promote breakdown of the BBB, and modifications induced by neonatal MSG treatment that could alter the behavior of the BBB. In conclusion, additional studies to better characterize the effects of neonatal MSG treatment on excitatory amino acids transporters, ionic exchangers, and efflux transporters, as well as the role of the signaling pathways mediated by erythropoietin and vascular endothelial growth factor in the cellular elements of the BBB, should be performed to identify the mechanisms underlying the increase in neurovascular permeability associated with excitotoxicity observed in several diseases and studied using neonatal MSG treatment. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  7. Multimodal imaging in a case of self-inflicted laser-induced maculopathy. (United States)

    Combillet, France; Saunier, Valentine; Rougier, Marie Bénédicte; Delyfer, Marie Noëlle; Korobelnik, Jean-Francois


    To describe the clinical and imaging findings in a case of self-inflicted handheld laser exposure. We evaluated multimodal imaging including fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography for a 32-year-old man with a history of repetitive self-inflicted handheld laser exposure. Funduscopic examination revealed bilateral and asymmetric yellow macular linear streaks with a vertical pattern in the superior macula. Curvilinear bands of dense hyperreflectivity extending from the ellipsoid zone of the photoreceptors and ending at the level of the outer plexiform layer were seen on SD-OCT immediately after injury. After intravenous high-dose corticosteroids during 3 days, the lesions decreased slightly. The recognition of characteristic self-inflicted handheld laser-induced lesions is paramount as laser pointer misuse has been increasing over the years.

  8. Self Inflicted Injuries among Children in United States - estimates from a nationwide emergency department sample.

    Directory of Open Access Journals (Sweden)

    Naseem Sulyman

    Full Text Available OBJECTIVE: The objectives of the current study are to provide nationally representative estimates of hospital based emergency department visits (ED attributed to self inflicted injuries and attempted suicides among children in United States; and to identify potential methods of such intentional self inflicted injuries and attempted suicides. METHODS: The Nationwide Emergency Department Sample (year 2007 was used. All ED visits occurring among children (aged ≤18 years with an External Cause of Injury for any of self inflicted injuries were selected. Outcomes examined include hospital ED charges and hospitalization charges. All estimates were projected to national levels. RESULTS: 77,420 visits to hospital based emergency departments were attributed to self inflicted injuries among children (26,045 males and 51,370 females. The average age of the ED visits was 15.7 years. 134 patients died in ED's (106 males and 28 females and 93 died in hospitals following in-patient admission (75 males and 18 females. A greater proportion of male ED visits were discharged routinely as opposed to female ED visits (51.1% versus 44%. A greater proportion of male ED visits also died in the emergency departments compared to female visits (0.4% versus 0.05%. 17,965 ED visits necessitated admission into same hospital. The mean charge for each ED visit was $1,874. Self inflicted injuries by poisoning were the most frequently reported sources accounting for close to 70% of all ED visits. CONCLUSIONS: Females comprise a greater proportion of ED visits attributed to self inflicted injuries. 227 children died either in the ED's or in hospitals. The current study results highlight the burden associated with such injuries among children.

  9. Gross and histopathological evaluation of human inflicted bruises in Danish slaughter pigs

    DEFF Research Database (Denmark)

    Barington, Kristiane; Agger, Jens Frederik Gramstrup; Nielsen, Søren Saxmose


    %), bruises had a tram-line pattern due to blunt trauma inflicted with long objects such as sticks. Other bruises reflected the use of tattoo-hammers, plastic paddles, double U profiles and chains. Histological evaluation of two bruises from a pig with multiple lesions was found insufficient to assess...

  10. Effects of Weaver Ants on Fruitfly and Disease-inflicted Postharvest ...

    African Journals Online (AJOL)

    fruit fly disease-inflicted postharvest losses of oranges in small-scale farming in Coast region,. Tanzania. The treatments consisted of weaver ant population estimated based on the number of nests (0, 2, 5 and 8) of weaver ants per tree and each was replicated three times. Orange fruits were randomly picked from farmers' ...

  11. Parent-Child Interactions, Peripheral Serotonin, and Self-Inflicted Injury in Adolescents (United States)

    Crowell, Sheila E.; Beauchaine, Theodore P.; McCauley, Elizabeth; Smith, Cindy J.; Vasilev, Christina A.; Stevens, Adrianne L.


    Self-inflicted injury in adolescence indicates significant emotional and psychological suffering. Although data on the etiology of self-injury are limited, current theories suggest that the emotional lability observed among self-injuring adolescents results from complex interactions between individual biological vulnerabilities and environmental…

  12. Culturally-inflicted child rights violation: a case of Khomba practice ...

    African Journals Online (AJOL)

    Therefore, the study focused on interrogating the nature, reasons and community perceptions on culturally-inflicted child rights violations that are associated with the Khomba practice among the Shangaan people in Chiredzi, Zimbabwe. This paper adopted a qualitative research design to capture the perceptions of 26 ...

  13. Income inequality, social capital and self-inflicted injury and violence-related mortality

    NARCIS (Netherlands)

    Huisman, M.; Oldehinkel, A. J.

    Background: The objective of the study was to investigate the relation of income inequality and indicators of social capital to self-inflicted injury mortality (suicide) and violence-related mortality, and to the share of total mortality that is due to these two causes of death in 35 developed

  14. Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

    DEFF Research Database (Denmark)

    Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.


    The ability of cannabinoid CB, receptors to influence glutamatergic excitatory neurotransmission has fueled interest in how these receptors and their endogenous ligands may interact in conditions of excitotoxic insults. The present study characterized the impact of stimulated and inhibited CB...

  15. Suicide and self-inflicted injury hospitalizations in Canada (1979 to 2014/15). (United States)

    Skinner, R; McFaull, S; Draca, J; Frechette, M; Kaur, J; Pearson, C; Thompson, W


    The purpose of this paper is to describe the trends and patterns of self-inflicted injuries, available from Canadian administrative data between 1979 and 2014/15, in order to inform and improve suicide prevention efforts. Suicide mortality and hospital separation data were retrieved from the Public Health Agency of Canada (PHAC) holdings of Statistics Canada's Canadian Vital Statistics: Death Database (CVS:D) (1979 to 2012); Canadian Socio-Economic Information Management System (CANSIM 2011, 2012); the Hospital Morbidity Database (HMDB) (1994/95 to 2010/11); and the Discharge Abstract Database (2011/12 to 2014/15). Mortality and hospitalization counts and rates were reported by sex, 5-year age groups and method. The Canadian suicide rate (males and females combined, all ages, age-sex standardized rate) has decreased from 14.4/100 000 (n = 3355) in 1979 to 10.4/100 000 (n = 3926) in 2012, with an annual percent change (APC) of -1.2% (95% CI: -1.3 to -1.0). However, this trend was not observed in both sexes: female suicide rates stabilized around 1990, while male rates continued declining over time-yet males still accounted for 75.7% of all suicides in 2012. Suffocation (hanging and strangulation) was the primary method of suicide (46.9%) among Canadians of all ages in 2012, followed by poisoning at 23.3%. In the 2014/15 fiscal year, there were 13 438 hospitalizations in Canada (excluding Quebec) associated with self-inflicted injuries-over 3 times the number of suicides. Over time females have displayed consistently higher rates of hospitalization for self-inflicted injury than males, with 63% of the total. Poisoning was reported as the most frequent means of self-inflicted harm in the fiscal year 2014/15, at 86% of all hospitalizations. Suicides and self-inflicted injuries continue to be a serious - but preventable - public health problem that requires ongoing surveillance.

  16. Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, B W; Noraberg, J; Jakobsen, B


    in corticostriatal slice cultures. The purpose was to examine the feasibility of these cultures for excitotoxic studies, and to demonstrate possible differential excitotoxic effects of KA and AMPA on striatal and cortical neurons. Slices of dorsolateral striatum with overlying neocortex were obtained from neonatal...... of the cytosolic enzyme lactate dehydrogenase (LDH) into the culture medium and loss of glutamic acid decarboxylase (GAD) activity in the tissue. Histological sections were also stained by the fluorescent dye Fluoro-Jade (FJ), for degenerating neurons and by immunocytochemical staining for gamma-aminobutyric acid...... density of Fluoro-Jade staining, (3) loss of GAD-activity in tissue homogenates, and (4) loss of GABA-immunostained neurons. We conclude that both differences between compounds (AMPA vs. KA) and brain areas (striatum vs. cortex) can be demonstrated in corticostriatal slice cultures, which in conjunction...

  17. Riluzole is a promising pharmacological inhibitor of bilirubin-induced excitotoxicity in the ventral cochlear nucleus. (United States)

    Han, Guo-Ying; Li, Chun-Yan; Shi, Hai-Bo; Wang, Ji-Ping; Su, Kai-Ming; Yin, Xin-Lu; Yin, Shan-Kai


    Bilirubin encephalopathy as a result of hyperbilirubinemia is a devastating neurological disorder that occurs mostly in the neonatal period. To date, no effective drug treatment is available. Glutamate-mediated excitotoxicity is likely an important factor causing bilirubin encephalopathy. Thus, drugs suppressing the overrelease of glutamate may protect the brain against bilirubin excitotoxicity. Riluzole is a prescription drug known for its antiglutamatergic function. This study was conducted in the rat's ventral cochlear nucleus, a structure highly sensitive to bilirubin toxicity, to find whether riluzole can be used to inhibit bilirubin toxicity. Electrophysiology changes were detected by perforated patch clamp technique. Calcium imaging using Rhod-2-AM as an indicator was used to study the intracellular calcium. Cell apoptosis and necrosis were measured by PI/Hoechst staining. In the absence of bilirubin, riluzole effectively decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and suppressed neuronal firing but did not change the amplitude of sEPSC and glutamate-activated currents (I(Glu)). Moreover, riluzole inhibited bilirubin-induced increases in the frequency of sEPSC and neuronal firing. Riluzole could prevent the bilirubin-induced increase in intracellular calcium, mediated by AMPA and NMDA receptors. Furthermore, riluzole significantly reduced bilirubin-induced cell death. These data suggest that riluzole can protect neurons in the ventral cochlear nucleus from bilirubin-induced hyperexcitation and excitotoxicity through reducing presynaptic glutamate release. © 2014 John Wiley & Sons Ltd.

  18. Comparison of the General Health, Self-Esteem and Social Support in Self-Inflicted Burn Patients and Non Self Inflicted Burn Patients of the Choromy Accidental and Burning Hospital of Ganaveh

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    MS Enayati


    Full Text Available ABSTRACT: Introduction & Objective: Self-inflicted burn is a violent method of suicide. Since our society faces lots of psychological, social, personal and economical problems due to self-inflicted burn, more survey for this event can assist us to know its causes and prevent from its occurrence. This research was carried out to compare general health, self- esteem and social support in patient's self-inflicted burn and non-self-inflicted burn of the Choromy accidental and burning hospital in Ganaveh. Materials & Methods: This is a descriptive – analytic study. The sample consisted of 60 inpatients burnt (males & females of the Choromy accidental and burning hospital (Ganaveh. The method of sampling was simple random. Participants completed the General Health Questionnaire (G.H.Q- 28 of Goldberg, Cooper Smith’s questionnaire of self–esteem and Philip’s social support scale. Multivariate analysis of variance (MANOVA and T-test were the major statistical analysis in this research. Results: The mean and standard deviation of the general health were 44.57 ± 14.65 for self-inflicted burn persons and for non - self inflicted burn they were 10.83 ± 6.27. In the self–esteem variable, the mean and the standard deviation were 57.90 ± 4.94 for self-inflicted burn persons and 55.47 ± 6.04 for non-self inflicted burn ones. Mean and standard deviation of whole social supporting were 20.40 ± 4.94 for self-inflicted burn persons and 23.73 ± 1.17 for non-self inflicted burn group. The findings showed significant differences between the two groups from viewpoint of general health and social supporting while there were no significant differences between two groups in case of self–esteem. Conclusion: There are a significant relationship between general health, social supporting and self-inflicted burn.Therefore, in order to prevent self inflicted burn it is suggested that we make a relationship between persons and societies, families, groups and

  19. Self-inflicted penetrating eye injuries using a razor blade: Case report

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    Price Nicholas


    Full Text Available Abstract Background A 23 year old white male with a history of social and behavioural problems attempted to blind himself chemically, with alcohol, and mechanically, with a razor blade. Methods Observational case report of a patient who self-inflicted bilateral scleral lacerations with a razor blade, after losing his job. Results The patient sustained bilateral inferior scleral perforations, with hypotony and a right traumatic cataract. He received urgent surgical repair, and prophylactic antibiotics. There were no retinal breaks or detachments. He later underwent successful cataract surgery to the right eye. Conclusion Self-inflicted ocular injury may be possible in non-psychotic patients, as a situational response to a life event. Urgent repair can completely restore vision in some cases. Referral for psychiatric counseling is mandatory.

  20. Autoextraction of Permanent Incisors and Self-Inflicted Orodental Trauma in a Severely Burned Child

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    Sultan Keles


    Full Text Available Autoextraction is one type of self-injurious behaviour. In the literature, self-injurious behaviours are observed in syndromes and genetic conditions. However, to the best of our knowledge, SIB and autoextraction in a severely burned patient have not been reported to date. This report describes the self-inflicted trauma and autoextraction in a severely burned child, and the management of the child during and after burn treatment.

  1. An unusual case of self-inflicted multiple needles injuries to eye

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    Shweta Gaur


    Full Text Available Self-inflicted eye injuries among psychiatric patients are rare but important group of ophthalmic conditions that require close cooperation between different medical specialties to ensure optimum care of the severely disturbed patient. They have been associated with a variety of disorders, including paranoid schizophrenia, drug-induced psychosis, obsessive-compulsive disorder, depression, mental retardation, and ritualistic behavior. It has been described in both adults and children, but occurs most commonly in young adults with acute or chronic psychoses.

  2. Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease. (United States)

    Nato, Giulia; Caramello, Alessia; Trova, Sara; Avataneo, Valeria; Rolando, Chiara; Taylor, Verdon; Buffo, Annalisa; Peretto, Paolo; Luzzati, Federico


    In the adult brain, subsets of astrocytic cells residing in well-defined neurogenic niches constitutively generate neurons throughout life. Brain lesions can stimulate neurogenesis in otherwise non-neurogenic regions, but whether local astrocytic cells generate neurons in these conditions is unresolved. Here, through genetic and viral lineage tracing in mice, we demonstrate that striatal astrocytes become neurogenic following an acute excitotoxic lesion. Similar to astrocytes of adult germinal niches, these activated parenchymal progenitors express nestin and generate neurons through the formation of transit amplifying progenitors. These results shed new light on the neurogenic potential of the adult brain parenchyma. © 2015. Published by The Company of Biologists Ltd.

  3. Make-up and love bites: two reports about exceptional cases of self-inflicted "injuries". (United States)

    Blaas, Verena; Manhart, Johannes; Büttner, Andreas


    Self-inflicted injuries and their differentiation from inflicted injuries may have severe legal implications. The detection of these injuries is an important task in clinical forensic medicine. We present two cases of skin discolorations caused by using make-up and suction of the skin which have only rarely been reported. In the first case a 19-year-old woman asserted she was punched against her left clavicle and her right eye by a perpetrator, and that during the following forced sexual intercourse she had been bitten on the neck. On medicolegal examination 3 days later dark blue, shimmering discolorations at her right eyebrow, the left side of the neck and the left clavicle were seen. At first sight these discolorations appeared as bruises; however, they could easily be removed by a simple wipe with a finger. In the second reported case a 23-year-old woman reported she had been assaulted by two men who forcefully pressed her against a wall, partially undressed her and forced her to touch and rub one man's penis. Medicolegal examination 32 h after the incident revealed several round to oval shaped, reddish to brown discolorations on both of her upper arms resembling so-called love bites created by suction. In both cases the preliminary investigation by the public prosecutor were closed. However, case 1 is still subject to legal investigations due to false incrimination. Self-infliction of injuries should always be considered in forensic examinations, even if they do not follow the classical pattern.

  4. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

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    Corinne Beurrier

    Full Text Available Ciliary neurotrophic factor (CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA was significantly reduced (by approximately 75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs, whose recovery was significantly higher in CNTF rats compared to controls (approximately 40% vs. approximately 7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (gamma-D-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.

  5. Conditioned Medium Reconditions Hippocampal Neurons against Kainic Acid Induced Excitotoxicity: An In Vitro Study

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    Pradeep Kumar K. Bevinahal


    Full Text Available Stem cell therapy is gaining attention as a promising treatment option for neurodegenerative diseases. The functional efficacy of grafted cells is a matter of debate and the recent consensus is that the cellular and functional recoveries might be due to “by-stander” effects of grafted cells. In the present study, we investigated the neuroprotective effect of conditioned medium (CM derived from human embryonic kidney (HEK cells in a kainic acid (KA induced hippocampal degeneration model system in in vitro condition. Hippocampal cell line was exposed to KA (200 µM for 24 hrs (lesion group whereas, in the treatment group, hippocampal cell line was exposed to KA in combination with HEK-CM (KA + HEK-CM. We observed that KA exposure to cells resulted in significant neuronal loss. Interestingly, HEK-CM cotreatment completely attenuated the excitotoxic effects of KA. In HEK-CM cotreatment group, the cell viability was ~85–95% as opposed to 47% in KA alone group. Further investigation demonstrated that treatment with HEK-CM stimulated the endogenous cell survival factors like brain derived neurotrophic factors (BDNF and antiapoptotic factor Bcl-2, revealing the possible mechanism of neuroprotection. Our results suggest that HEK-CM protects hippocampal neurons against excitotoxicity by stimulating the host’s endogenous cell survival mechanisms.

  6. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J


    The excitotoxic profiles of (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), (RS)-2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartate (NMDA) were evaluated using cellular uptake of propidium iodide (PI) as a measure......) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed...... by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

  7. The GluK4 kainate receptor subunit regulates memory, mood, and excitotoxic neurodegeneration. (United States)

    Lowry, E R; Kruyer, A; Norris, E H; Cederroth, C R; Strickland, S


    Though the GluK4 kainate receptor subunit shows limited homology and a restricted expression pattern relative to other kainate receptor subunits, its ablation results in distinct behavioral and molecular phenotypes. GluK4 knockout mice demonstrated impairments in memory acquisition and recall in a Morris water maze test, suggesting a previously unreported role for kainate receptors in spatial memory. GluK4 knockout mice also showed marked hyperactivity and impaired pre-pulse inhibition, thereby mirroring two of the hallmark endophenotypes of patients with schizophrenia and bipolar disorder. Furthermore, we found that GluK4 is a key mediator of excitotoxic neurodegeneration: GluK4 knockout mice showed robust neuroprotection in the CA3 region of the hippocampus following intrahippocampal injection of kainate and widespread neuroprotection throughout the hippocampus following hypoxia-ischemia. Biochemical analysis of kainate- or sham-treated wild-type and GluK4 knockout hippocampal tissue suggests that GluK4 may act through the JNK pathway to regulate the molecular cascades that lead to excitotoxicity. Together, our findings suggest that GluK4 may be relevant to the understanding and treatment of human neuropsychiatric and neurodegenerative disorders. Copyright © 2013 IBRO. All rights reserved.

  8. Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP. (United States)

    Xu, Jian; Kurup, Pradeep; Zhang, Yongfang; Goebel-Goody, Susan M; Wu, Peter H; Hawasli, Ammar H; Baum, Matthew L; Bibb, James A; Lombroso, Paul J


    NMDA receptor (NMDAR)-mediated excitotoxicity plays an important role in several CNS disorders, including epilepsy, stroke, and ischemia. Here we demonstrate the involvement of striatal-enriched protein tyrosine phosphatase (STEP) in this critical process. STEP(61) is an alternatively spliced member of the family that is present in postsynaptic terminals. In an apparent paradox, STEP(61) regulates extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, two proteins with opposing functions; activated p38 promotes cell death, whereas activated ERK1/2 promotes cell survival. We found that synaptic stimulation of NMDARs promoted STEP(61) ubiquitination and degradation, concomitant with ERK1/2 activation. In contrast, extrasynaptic stimulation of NMDARs invoked calpain-mediated proteolysis of STEP(61), producing the truncated cleavage product STEP(33) and activation of p38. The calpain cleavage site on STEP was mapped to the kinase interacting motif, a domain required for substrate binding. As a result, STEP(33) neither interacts with nor dephosphorylates STEP substrates. A synthetic peptide spanning the calpain cleavage site efficiently reduced STEP(61) degradation and attenuated p38 activation and cell death in slice models. Furthermore, this peptide was neuroprotective when neurons were subjected to excitotoxicity or cortical slices were exposed to ischemic conditions. These findings suggest a novel mechanism by which differential NMDAR stimulation regulates STEP(61) to promote either ERK1/2 or p38 activation and identifies calpain cleavage of STEP(61) as a valid target for the development of neuroprotective therapy.

  9. Self-inflicted oral trauma in a baby with Moebius syndrome. (United States)

    Guimarães, Lizandra Ferrari; Janini, Maria Elisa; Vieira, Aurea Simone Barroso; Maia, Lucianne Cople; Primo, Laura Guimarães


    Moebius syndrome (MS) is a rare disorder mainly characterized by bi- or unilateral palsy of the facial and abducens nerves. Among the various orofacial characteristics related to this syndrome, the following are pointed out, difficulty with sucking, tongue malformation, mandibular hypoplasia, saliva drooling, arched palate and micrognathia. In spite of the diversity of oral features described for these patients, self-inflicted oral trauma has not yet been reported. Therefore, the purposes of the present report were to describe an unusual case of a baby with Moebius syndrome who had a parafunctional habit that resulted in a persistent traumatic lesion of the lower lip, and discuss the treatment performed.

  10. Retroperitoneal migration of a self-inflicted ballpoint pen via the urethra

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    Jose Cury


    Full Text Available Numerous accounts documenting the introduction of foreign bodies into the urinary bladder have been reported. These foreign bodies are typically self-inserted via urethral but migration from adjacent organs by an ulcerative process and penetrating injuries are also reported. However, "contrary" migration of a self-inflicted vesical foreign body to the retroperitoneum was not previously reported in literature. We report here a case of a ballpoint pen self-inserted via urethral by a female patient, which was identified in retroperitoneal position years later.

  11. Self-Inflicted Needle Injuries to the Eye: A Curing Pain

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    Shahrokh Amiri


    Full Text Available There are few reports of severe self-injury to eyes in patients with schizophrenia. We report on a 41-year-old woman, primarily visiting for symptoms of endophthalmitis resulting from self-inflicted needles. Further evaluations established the diagnosis of schizophrenia because of arguing and commenting on auditory hallucinations and negative symptoms including social isolation, decreased self-care, blunt affect, and a monotone voice. The patient had been suffering from auditory hallucinations for several years and found relief in bodily pain caused by needles. The patient received 6 mg of risperidone. Hallucinations were resolved and self-injury behaviour was not repeated.

  12. Suicide and self-inflicted injury hospitalizations in Canada (1979 to 2014/15

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    R. Skinner


    Full Text Available Introduction: The purpose of this paper is to describe the trends and patterns of self-inflicted injuries, available from Canadian administrative data between 1979 and 2014/15, in order to inform and improve suicide prevention efforts. Methods: Suicide mortality and hospital separation data were retrieved from the Public Health Agency of Canada (PHAC holdings of Statistics Canada's Canadian Vital Statistics: Death Database (CVS:D (1979 to 2012; Canadian Socio-Economic Information Management System (CANSIM 2011, 2012; the Hospital Morbidity Database (HMDB (1994/95 to 2010/11; and the Discharge Abstract Database (2011/12 to 2014/15. Mortality and hospitalization counts and rates were reported by sex, 5-year age groups and method. Results: The Canadian suicide rate (males and fe­males combined, all ages, age-sex standardized rate has decreased from 14.4/100 000 (n = 3355 in 1979 to 10.4/100 000 (n = 3926 in 2012, with an annual percent change (APC of ­ 1.2% (95% CI: ­1.3 to ­1.0. However, this trend was not observed in both sexes: female suicide rates stabilized around 1990, while male rates continued declining over time—yet males still accounted for 75.7% of all suicides in 2012. Suffocation (hanging and strangulation was the primary method of suicide (46.9% among Canadians of all ages in 2012, followed by poisoning at 23.3%. In the 2014/15 fiscal year, there were 13 438 hospitalizations in Canada (excluding Quebec associated with self-in­flicted injuries—over 3 times the number of suicides. Over time females have displayed con­sistently higher rates of hospitalization for self-inflicted injury than males, with 63% of the total. Poisoning was reported as the most frequent means of self-inflicted harm in the fiscal year 2014/15, at 86% of all hospitalizations. Conclusion: Suicides and self-inflicted injuries continue to be a serious—but preventable—public health problem that requires ongoing surveillance.

  13. Munchausen's syndrome or pure self-mutilation? A case of self-inflicted tendon injury

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    Burak Kaya


    Full Text Available Self-mutilation (self-harm or self-injury is any intentional injury to one's own body most often done without suicidal intentions. The most common form of self-mutilation is skin cutting. Munchausen's syndrome is an extreme type of factitious disorder in which the individuals seek for medical help for factitious illnesses to draw attention and sympathy. In this case report we present a 40 years old male patient with self-inflicted wrist cut who imitated the symptoms of tendon and nerve injuries. [Hand Microsurg 2014; 3(3.000: 83-86

  14. "Tetracycline hydrochloride chemical burn" as self-inflicted mucogingival injury: A rare case report

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    Mundoor Manjunath Dayakar


    Full Text Available Injuries to oral soft tissue can be accidental, iatrogenic, and factitious trauma. Chemical, thermal, and physical agents are the main causative agents for oral soft-tissue burns. The present case describes the chemical burn of oral mucosa caused by tetracycline hydrochloride and its management. Diagnosis was made on the basis of definitive history elicited from the patient. The early detection of the lesion by the patient and immediate institution of therapeutic measures ensure a rapid cure and possible prevention of further mucogingival damage. In addition, we believe that proper guidance and education of the patient is an important prophylactic measure in preventing this self-inflicting injury.

  15. [The classification of the injuries inflicted to the human body by gunshots from the pneumatic weapons]. (United States)

    Kozachenko, I N


    The classification of the injuries inflicted to the human body by gunshots from the pneumatic weapons remains to be developed. The objective of the present work was to elaborate the classification of the injuries caused by gunshots from the pneumatic weapons based on the analysis of 98 expert and acts of forensic medical expertises (surveys) of living subjects (n=76) and corpses (n=22) affected by gunshots from the pneumatic weapons. These materials were collected from the bureaus of forensic medical expertise in different regions of the Ukraine during the period from 2006 till 2015. In addition, scientific publications concerned with the problem of interest were used along with the relevant explanatory and terminological dictionaries. The terminology and the conceptual framework proposed by the author in the earlier papers provided a basis for the development of the first standard classification of the injuries inflicted to the human body by gunshots from the pneumatic weapons categorized into 15 groups. It is believed that this classification will lay the foundation for the common approach of forensic medical experts to the examination and analysis of the data on the gunshots from the pneumatic weapons used to be found on the bodies of living subjects and the corpses. Moreover, it may be useful for the clinicians in their diagnostic and therapeutic practices and for the legal practitioners engaged in the quality assessment of the results of forensic medical expertises. It is recommended to present information about the gunshots from the pneumatic weapons in the accounting documents in a separate line.


    Rabiolo, Alessandro; Sacconi, Riccardo; Giuffrè, Chiara; Corbelli, Eleonora; Carnevali, Adriano; Querques, Lea; Sarraf, David; Freund, K Bailey; Sadda, SriniVas; Bandello, Francesco; Querques, Giuseppe


    To report a case of factitious self-inflicted handheld laser-induced maculopathy. A 29-year-old man presented to our clinic complaining of a step-wise progressive loss of vision that abruptly began in his left eye but then became bilateral. He underwent comprehensive ocular examination, including visual acuity testing, biomicroscopic, dilated funduscopic examination, structural optical coherence tomography, en face structural optical coherence tomography, optical coherence tomography angiography, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Visual acuity was 20/200 in both eyes. Although the multimodal imaging was highly consistent with handheld laser-induced maculopathy, the patient continued to deny this behavior. Self-inflicted handheld laser-induced maculopathy may be a novel manifestation of factitious disorder. Clinical suspicion for this should remain high in the presence of the signature multimodal retinal findings despite denial by the patient. This category of patients could benefit from psychiatric referral, to prevent further ocular or extra-ocular self-injury.

  17. Erysipelothrix rhusiopathiae isolated from gull-inflicted wounds in southern right whale calves. (United States)

    Fiorito, Carla D; Bentancor, Adriana; Lombardo, Daniel; Bertellotti, Marcelo


    Southern right whales Eubalaena australis from Peninsula Valdés, Argentina, show wounds produced by kelp gulls Larus dominicanus that feed on the whales' dorsal skin and blubber. During the 2013 whale season, several calves were reported showing kelp gull injuries with a swollen area surrounded by rhomboid-shaped raised edges. Samples from 9 calves were taken in order to establish the etiology of these rhomboid-shaped wounds; 2 calves (one living, one dead) showed gull-inflicted injuries with rhomboid-shaped edges. Samples from the dead calf were histologically characterized by the presence of dermal congestion, suppurative dermatitis and panniculitis, necrotizing vasculitis and vascular thrombosis. Erysipelothrix rhusiopathiae was detected by culture and PCR in samples from both calves. In this study we report, for the first time to our knowledge, the isolation of E. rhusiopathiae from wounds produced by gull attacks on southern right whale calves, supplying evidence that these wounds may act as an entry route for pathogens. This work provides new information about the consequences of gull-inflicted injuries for whale health.

  18. Management of self-inflicted dental injuries with various nonsurgical techniques: Case series

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    Ganesh Ranganath Jadhav


    Full Text Available Children have a common habit of exploring carious or traumatically exposed teeth using various foreign objects such as metal screws, staple pins, darning needles, pencil leads, beads, paper clip, and toothpicks, which may sometimes break inside the pulp chamber or root canal. Majority of such cases are asymptomatic and hence diagnosed accidentally on routine radiographic examination. However, embedded foreign objects may sometimes act as a potential source of infection and are convoyed with pain or recurrent swelling. Dentists must be aware of the self-inflicted dental injury, its consequences, and selection of the all-inclusive treatment strategies giving due consideration to cost-benefit ratio of the different treatment options. This case series highlights the possible dental consequences of placing foreign objects in the mouth and various management strategies. Four cases of self-inflicted dental injuries involving patients aged 10–20 years are presented and investigated from the endodontic, pedodontic, and psychiatric viewpoints. In all cases, the cause has been easily identified by clinical appearance corroborated with a good history. This paper discusses a nonsurgical technique to retrieve these objects from the root canal with minimal damage to internal tooth structure.

  19. Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding

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    Svetlana A. Ivanova


    Full Text Available A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs: postsynaptic density- (PSD- 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.

  20. β-Amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis

    NARCIS (Netherlands)

    Harkany, T.; Ábrahám, I.; Timmerman, W.; Laskay, G.; Tóth, B.; Sasvári, M.; Kónya, C.; Sebens, J.B.; Korf, J.; Nyakas, C.; Zarándi, M.; Soós, K.; Penke, B.; Luiten, P.G.M.


    Whereas a cardinal role for β-amyloid protein (Aβ) has been postulated as a major trigger of neuronal injury in Alzheimer's disease, the pathogenic mechanism by which Aβ deranges nerve cells remains largely elusive. Here we report correlative in vitro and in vivo evidence that an excitotoxic cascade

  1. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M


    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this eff...

  2. Brimonidine blocks glutamate excitotoxicity-induced oxidative stress and preserves mitochondrial transcription factor a in ischemic retinal injury.

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    Dongwook Lee

    Full Text Available Glutamate excitotoxicity-induced oxidative stress have been linked to mitochondrial dysfunction in retinal ischemia and optic neuropathies including glaucoma. Brimonindine (BMD, an alpha 2-adrenergic receptor agonist, contributes to the neuroprotection of retinal ganglion cells (RGCs against glutamate excitotoxicity or oxidative stress. However, the molecular mechanisms of BMD-associated mitochondrial preservation in RGC protection against glutamate excitotoxicity-induced oxidative stress following retinal ischemic injury remain largely unknown. Here, we tested whether activation of alpha 2 adrenergic receptor by systemic BMD treatment blocks glutamate excitotoxicity-induced oxidative stress, and preserves the expression of mitochondrial transcription factor A (Tfam and oxidative phosphorylation (OXPHOS complex in ischemic retina. Sprague-Dawley rats received BMD (1 mg/kg/day or vehicle (0.9% saline systemically and then transient ischemia was induced by acute intraocular pressure elevation. Systemic BMD treatment significantly increased RGC survival at 4 weeks after ischemia. At 24 hours, BMD significantly decreased Bax expression but increased Bcl-xL and phosphorylated Bad protein expression in ischemic retina. Importantly. BMD significantly blocked the upregulations of N-methyl-D-aspartate receptors 1 and 2A protein expression, as well as of SOD2 protein expression in ischemic retina at 24 hours. During the early neurodegeneration following ischemic injury (12-72 hours, Tfam and OXPHOS complex protein expression were significantly increased in vehicle-treated retina. At 24 hours after ischemia, Tfam immunoreactivity was increased in the outer plexiform layer, inner nuclear layer, inner plexiform layer and ganglion cell layer. Further, Tfam protein was expressed predominantly in RGCs. Finally, BMD preserved Tfam immunoreactivity in RGCs as well as Tfam/OXPHOS complex protein expression in the retinal extracts against ischemic injury. Our

  3. Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

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    Shan Zou

    Full Text Available In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA and sodium (Nav channels trigger excitotoxic neuron death. Na(+, Ca(++ and H2O influx into affected neurons elicits swelling (increased cell volume and pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix. Though usually conflated in injured tissue, cell swelling and blebbing are distinct processes. Around an injury core, salvageable neurons could be mildly swollen without yet having suffered the bleb-type membrane damage that, by rendering channels leaky and pumps dysfunctional, exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal inflation signifies non-lethal osmotic swelling versus blebbing should further efforts to salvage injury-penumbra neurons. To assess whether the mechanical properties of osmotically-swollen versus excitotoxically-blebbing neurons might be cytomechanically distinguishable, we measured cortical neuron elasticity (gauged via atomic force microscopy (AFM-based force spectroscopy upon brief exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel activators, NMDA and veratridine. Though unperturbed by solution exchange per se, elasticity increased abruptly with hypotonicity, with NMDA and with veratridine. Neurons then invariably softened towards or below the pre-treatment level, sometimes starting before the washout. The initial channel-mediated stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++]int-mediated submembrane actomyosin contractility. The subsequent softening to below-control levels is consistent with the onset of a lethal level of bleb damage. These findings indicate that dissection/identification of molecular events during the excitotoxic transition from stiff/swollen to soft/blebbing is warranted and should be

  4. Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions.

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    Niamh M C Connolly

    Full Text Available Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK, re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK-mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity-induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult.

  5. Procyanidin B2 Protects Neurons from Oxidative, Nitrosative, and Excitotoxic Stress

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    Taylor C. Sutcliffe


    Full Text Available The aberrant generation of oxygen and nitrogen free radicals can cause severe damage to key cellular components, resulting in cell apoptosis. Similarly, excitotoxicity leads to protease activation and mitochondrial dysfunction, which subsequently causes cell death. Each of these factors play critical roles in the neuronal cell death underlying various neurodegenerative diseases. Procyanidin B2 (PB2 is a naturally occurring polyphenolic compound found in high concentrations in cocoa, apples, and grapes. Here, we examine the neuroprotective effects of PB2 in primary cultures of rat cerebellar granule neurons (CGNs exposed to various stressors. CGNs were pre-incubated with PB2 and then neuronal stress was induced as described below. Mitochondrial oxidative stress was triggered with HA14-1, an inhibitor of the pro-survival Bcl-2 protein which induces glutathione-sensitive apoptosis. Glutamate and glycine were used to induce excitotoxicity. Sodium nitroprusside, a nitric oxide generating compound, was used to induce nitrosative stress. We observed significant dose-dependent protection of CGNs with PB2 for all of the above insults, with the greatest neuroprotective effect being observed under conditions of nitrosative stress. Intriguingly, the neuroprotective effect of PB2 against nitric oxide was superoxide-dependent, as we have recently shown for other catechol antioxidants. Finally, we induced neuronal stress through the removal of depolarizing extracellular potassium and serum (5K conditions, which is a classical model of intrinsic apoptosis in CGNs. PB2 did not display any significant protection against 5K-induced apoptosis at any concentration tested. We conclude that PB2 offers neuronal protection principally as an antioxidant by scavenging reactive oxygen and nitrogen species instead of through modulation of pro-survival cell signaling pathways. These findings suggest that PB2 may be an effective neuroprotective agent for the treatment of

  6. Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36 (United States)

    Corsini, Silvia; Tortora, Maria; Rauti, Rossana; Nistri, Andrea


    Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca2+ transients time locked among nearby HMs, whose number fell by about 30% 4 h later. As nicotine or the gap junction blocker carbenoxolone suppressed bursting, we studied connexin 36 (Cx36), which constitutes gap junctions in neurons and found it largely expressed by HMs. Cx36 was downregulated when nicotine or carbenoxolone was co-applied with TBOA. Expression of Cx36 was preferentially observed in cytosolic rather than membrane fractions after nicotine and TBOA, suggesting protein redistribution with no change in synthesis. Nicotine raised the expression of heat shock protein 70 (Hsp70), a protective factor that binds the apoptotic-inducing factor (AIF) whose nuclear translocation is a cause of cell death. TBOA increased intracellular AIF, an effect blocked by nicotine. These results indicate that activation of neuronal nicotinic receptors is an early tool for protecting motoneurons from excitotoxicity and that this process is carried out via the combined decrease in Cx36 activity, overexpression of Hsp70 and fall in AIF translocation. Thus, retarding or inhibiting HM death may be experimentally achieved by targeting one of these processes leading to motoneuron death. PMID:28617431

  7. Mandibular osteonecrosis and teeth exfoliation after herpes zoster infection in an HIV-inflicted individual

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    Preeti Chawla Arora


    Full Text Available Herpes zoster (HZ infection of the maxillary and mandibular divisions of the trigeminal nerve manifests orally as unilateral vesicular eruption localized to the skin and mucus membrane of the dermatome innervated by the trigeminal nerve. Herpes zoster infection has been observed in immunocompromised states like uncontrolled diabetes, cancer chemotherapy, lymphoproliferative diseases, and recently in HIV-positive patients. There are only a few case reports of osteonecrosis due to HZ in an HIV-positive patient in an Indian population, this being the first in a North Indian population. We propose that osteonecrosis should be considered as a strong indicator of HIV infection, especially in a developing country like India. The present case highlights the complexities which can arise in an HIV-inflicted individual suffering from HZ infection. Early diagnosis of such infections can lead to effective treatment and prevention of complications.

  8. A unique case presentation of recurrent self-inflicted chemical burns

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    Jennifer Kesey


    Full Text Available A 52-year-old man was admitted to multiple burn facilities five years after an initial work-related chemical burn to his hand, with the claim of a non-healing burn. Further investigation identified characteristics of self-inflicted burn for primary and secondary gain. A literature review of clinically relevant case studies is presented to aid in the identification and diagnosis of suspected factitious illness. Factitious disorders of the hand are frequently under-reported due to variability in presentation, difficulty in detection, and the need for repeat observations necessary for psychological diagnosis. This case serves to highlight key techniques in clinical approach and management for malingering disorders of the upper extremity.

  9. Repetitive urges to inflict burns: An unusual presentation of impulse control disorder

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    Arghya Pal


    Full Text Available Impulse control disorders (ICDs are characterized by an inability to resist an intense impulse or drive to perform a particular act that is excessive and/or harmful to self/others. Till date, there is no published report of an ICD presenting with repetitive urges to inflict burns. We describe the case of an adult male in regular follow-up for 6 months who presented with intense, irresistible, and repetitive urges and acts of causing burns on his skin for past 1 year. The phenomenology shared the core qualities described for ICDs and patient showed adequate response to treatment. The case report describes an unusual type of ICD classifiable as not otherwise specified. More clinical and research attention is warranted toward ICDs in general, with implications for ICD-11.

  10. Epidemiology and Outcome of Self-Inflicted Burns at Pakistan Institute of Medical Sciences, Islamabad (United States)

    Saaiq, Muhammad; Ashraf, Bushra


    BACKGROUND Self-inflicted burn injuries carry considerable mortality and morbidity among otherwise fit young individuals. This study assessed the epidemiologic pattern and outcome of these injuries in a burn care facility in Pakistan. METHODS The study was carried out at Pakistan Institute of Medical Sciences (PIMS) Burn Care Centre in Islamabad over a period of 2 years. It included all adult patients of either gender, aged over 14 years who presented as cases of burn suicides and attempted burn suicides during the study period. Convenience sampling technique was employed. The sociodemographic profile of the patients, motives underlying the act of self-immolation, any underlying psychiatric illness, alcohol abuse, total body surface area (TBSA) burnt, depth of burn injury, associated inhalation injury, duration of hospital stay, and mortality were all recorded. RESULTS Seventy five patients (80.64%) were female while 18 patients (19.35%) were male. The overall mean age was 26.89±6.1 years (range=15-52 years). The affected TBSA ranged from 15%-100% with an overall mean of 69.30±25.42%. The hospital stay ranged from 1-37 days with a mean of 7.16±6.60 days. Marital conflicts constituted the most frequent motive underlying the suicidal attempts (n=57; 61.29%) followed by failed love affairs (n=9; 9.67%). There was an overall mortality of 84.95%. The most common sufferers of self inflicted burn injuries were young, married, illiterate housewives who were resident of rural area. Getting marriage was the most common triggering cause for such injuries. CONCLUSION There is need to institute appropriate preventive measures to address the issue in a national perspective. PMID:25489533

  11. Student-inflicted injuries to staff in schools: comparing risk between educators and non-educators. (United States)

    Schofield, Katherine E; Ryan, Andrew D; Stroinski, Craig


    Student-inflicted injury to staff in the educational services sector is a growing concern. Studies on violence have focused on teachers as victims, but less is known about injuries to other employee groups, particularly educational assistants. Inequities may be present, as educational assistants and non-educators may not have the same wage, benefits, training and employment protections available to them as professional educators. We identified risk factors for student-related injury and their characteristics among employees in school districts. Workers' compensation data were used to identify incidence and severity of student-related injury. Rates were calculated using negative binomial regression; risk factors were identified using multivariate models to calculate rate ratios (RR) and 95% CIs. Over 26% of all injuries were student-related; 8% resulted in lost work time. Special and general education assistants experienced significantly increased risk of injury (RR=6.0, CI 5.05 to 7.15; RR=2.07, CI 1.40 to 3.07) as compared with educators. Risk differed by age, gender and school district type. Text analyses categorised student-related injury. It revealed injury from students acting out occurred most frequently (45.4%), whereas injuries involving play with students resulted in the highest percentage of lost-time injuries (17.7%) compared with all interaction categories. Student-inflicted injury to staff occurs frequently and can be severe. Special education and general assistants bear the largest burden of injury compared with educators. A variety of prevention techniques to reduce injury risk and severity, including policy or environmental modifications, may be appropriate. Equal access to risk reduction methods for all staff should be prioritised. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Animal-inflicted open wounds in rural Turkey: lessons learned and a proposed treatment algorithm for uncertain scenarios. (United States)

    Sezgin, Billur; Ljohiy, Mbaraka; Akgol Gur, Sultan Tuna


    Uncertainty in the management of animal-inflicted injuries, especially in rural settings, usually results in a general approach to leave all wounds to heal with secondary intention, which can lead to unsightly scarring and functional loss. This study focusus on different circumstances dealt with by plastic surgeons in a rural setting in Turkey and aims to configure what the general approach should be through an analysis of a wide spectrum of patients. Between June 2013 and December 2014, 205 patients who presented to the emergency department for animal-inflicted injuries were retrospectively analysed. Patients who consulted for plastic surgery were included in the analysis to determine which wounds require further attention. Patients with past animal-inflicted injuries who presented to the outpatient plastic surgery clinic with concerns such as non-healing open wounds or cosmetic or functional impairment were also evaluated. Statistical analysis demostrated a significantly lower rate of infection encountered in animal-inflicted open wounds (AIOWs) of patients who consulted for plastic surgery from the emergency department than those who presented to the outpatient clinic (P wounds is their potential for infection, but this does not mean that every wound will be infected. The most important factor is being able to distinguish wounds that have a higher potential for infection and to select the type of wound management accordingly. An algorithm has been proposed as a guidance for the management of AIOWs, which covers the approach towards both domestic and stray animal-inflicted injuries. © 2015 Inc and John Wiley & Sons Ltd.

  13. The volatile anesthetic methoxyflurane protects motoneurons against excitotoxicity in an in vitro model of rat spinal cord injury. (United States)

    Shabbir, A; Bianchetti, E; Nistri, A


    Neuroprotection of the spinal cord during the early phase of injury is an important goal to determine a favorable outcome by prevention of delayed pathological events, including excitotoxicity, which otherwise extend the primary damage and amplify the often irreversible loss of motor function. While intensive care and neurosurgical intervention are important treatments, effective neuroprotection requires further experimental studies focused to target vulnerable neurons, particularly motoneurons. The present investigation examined whether the volatile general anesthetic methoxyflurane might protect spinal locomotor networks from kainate-evoked excitotoxicity using an in vitro rat spinal cord preparation as a model. The protocols involved 1h excitotoxic stimulation on day 1 followed by electrophysiological and immunohistochemical testing on day 2. A single administration of methoxyflurane applied together with kainate (1h), or 30 or even 60 min later prevented any depression of spinal reflexes, loss of motoneuron excitability, and histological damage. Methoxyflurane per se temporarily decreased synaptic transmission and motoneuron excitability, effects readily reversible on washout. Spinal locomotor activity recorded as alternating electrical discharges from lumbar motor pools was fully preserved on the second day after application of methoxyflurane together with (or after) kainate. These data suggest that a volatile general anesthetic could provide strong electrophysiological and histological neuroprotection that enabled expression of locomotor network activity 1 day after the excitotoxic challenge. It is hypothesized that the benefits of early neurosurgery for acute spinal cord injury (SCI) might be enhanced if, in addition to injury decompression and stabilization, the protective role of general anesthesia is exploited. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury

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    Chiu Li Shan


    Full Text Available Cationic arginine-rich and poly-arginine peptides (referred to as CARPs have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model, R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

  15. Purinergic signaling induces cyclooxygenase-1-dependent prostanoid synthesis in microglia: roles in the outcome of excitotoxic brain injury.

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    Josef Anrather

    Full Text Available Cyclooxygenases (COX are prostanoid synthesizing enzymes constitutively expressed in the brain that contribute to excitotoxic neuronal cell death. While the neurotoxic role of COX-2 is well established and has been linked to prostaglandin E(2 synthesis, the role of COX-1 is not clearly understood. In a model of N-Methyl-D-aspartic acid (NMDA induced excitotoxicity in the mouse cerebral cortex we found a distinctive temporal profile of COX-1 and COX-2 activation where COX-1, located in microglia, is responsible for the early phase of prostaglandin E(2 synthesis (10 minutes after NMDA, while both COX-1 and COX-2 contribute to the second phase (3-24 hours after NMDA. Microglial COX-1 is strongly activated by ATP but not excitatory neurotransmitters or the Toll-like receptor 4 ligand bacterial lipopolysaccharide. ATP induced microglial COX-1 dependent prostaglandin E(2 synthesis is dependent on P2X7 receptors, extracellular Ca(2+ and cytoplasmic phospholipase A2. NMDA receptor activation induces ATP release from cultured neurons leading to microglial P2X7 receptor activation and COX-1 dependent prostaglandin E(2 synthesis in mixed microglial-neuronal cultures. Pharmacological inhibition of COX-1 has no effect on the cortical lesion produced by NMDA, but counteracts the neuroprotection exerted by inhibition of COX-2 or observed in mice lacking the prostaglandin E(2 receptor type 1. Similarly, the neuroprotection exerted by the prostaglandin E(2 receptor type 2 agonist butaprost is not observed after COX-1 inhibition. P2X7 receptors contribute to NMDA induced prostaglandin E(2 production in vivo and blockage of P2X7 receptors reverses the neuroprotection offered by COX-2 inhibition. These findings suggest that purinergic signaling in microglia triggered by neuronal ATP modulates excitotoxic cortical lesion by regulating COX-1 dependent prostanoid production and unveil a previously unrecognized protective role of microglial COX-1 in excitotoxic brain

  16. Vampire bat salivary plasminogen activator (desmoteplase) inhibits tissue-type plasminogen activator-induced potentiation of excitotoxic injury. (United States)

    Reddrop, Courtney; Moldrich, Randal X; Beart, Philip M; Farso, Mark; Liberatore, Gabriel T; Howells, David W; Petersen, Karl-Uwe; Schleuning, Wolf-Dieter; Medcalf, Robert L


    In contrast to tissue-type plasminogen activator (tPA), vampire bat (Desmodus rotundus) salivary plasminogen activator (desmoteplase [DSPA]) does not promote excitotoxic injury when injected directly into the brain. We have compared the excitotoxic effects of intravenously delivered tPA and DSPA and determined whether DSPA can antagonize the neurotoxic and calcium enhancing effects of tPA. The brain striatal region of wild-type c57 Black 6 mice was stereotaxically injected with N-methyl-d-Aspartate (NMDA); 24 hour later, mice received an intravenous injection of tPA or DSPA (10 mg/kg) and lesion size was assessed after 24 hours. Cell death and calcium mobilization studies were performed using cultures of primary murine cortical neurons. NMDA-mediated injury was increased after intravenous administration of tPA, whereas no additional toxicity was seen after administration of DSPA. Unlike DSPA, tPA enhanced NMDA-induced cell death and the NMDA-mediated increase in intracellular calcium levels in vitro. Moreover, the enhancing effects of tPA were blocked by DSPA. Intravenous administration of tPA promotes excitotoxic injury, raising the possibility that leakage of tPA from the vasculature into the parenchyma contributes to brain damage. The lack of such toxicity by DSPA further encourages its use as a thrombolytic agent in the treatment of ischemic stroke.

  17. Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

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    Marina Rubio

    Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

  18. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

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    Verónica Pérez-De La Cruz


    Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

  19. Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons. (United States)

    Eitan, Erez; Braverman, Carmel; Tichon, Ailone; Gitler, Daniel; Hutchison, Emmette R; Mattson, Mark P; Priel, Esther


    Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors: a sub-lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress.

  20. Normobaric hyperoxia is associated with increased cerebral excitotoxicity after severe traumatic brain injury. (United States)

    Quintard, Hervé; Patet, Camille; Suys, Tamarah; Marques-Vidal, Pedro; Oddo, Mauro


    Normobaric oxygen therapy is frequently applied in neurocritical care, however, whether supplemental FiO2 has beneficial cerebral effects is still controversial. We examined in patients with severe traumatic brain injury (TBI) the effect of incremental FiO2 on cerebral excitotoxicity, quantified by cerebral microdialysis (CMD) glutamate. This was a retrospective analysis of a database of severe TBI patients monitored with CMD and brain tissue oxygen (PbtO2). The relationship of FiO2--categorized into four separate ranges (80 %)--with CMD glutamate was examined using ANOVA with Tukey's post hoc test. A total of 1,130 CMD samples from 36 patients--monitored for a median of 4 days--were examined. After adjusting for brain (PbtO2, intracranial pressure, cerebral perfusion pressure, lactate/pyruvate ratio, Marshall CT score) and systemic (PaCO2, PaO2, hemoglobin, APACHE score) covariates, high FiO2 was associated with a progressive increase in CMD glutamate [8.8 (95 % confidence interval 7.4-10.2) µmol/L at FiO2 80 %; multivariate-adjusted p CMD glutamate was lower for samples with normal versus low PbtO2 40 % vs. FiO2 > 60 %). Hyperoxia (PaO2 > 150 mmHg) was also associated with increased CMD glutamate (adjusted p oxygen may aggravate secondary brain damage after severe TBI.

  1. Acidosis-Induced Dysfunction of Cortical GABAergic Neurons through Astrocyte-Related Excitotoxicity. (United States)

    Huang, Li; Zhao, Shidi; Lu, Wei; Guan, Sudong; Zhu, Yan; Wang, Jin-Hui


    Acidosis impairs cognitions and behaviors presumably by acidification-induced changes in neuronal metabolism. Cortical GABAergic neurons are vulnerable to pathological factors and their injury leads to brain dysfunction. How acidosis induces GABAergic neuron injury remains elusive. As the glia cells and neurons interact each other, we intend to examine the role of the astrocytes in acidosis-induced GABAergic neuron injury. Experiments were done at GABAergic cells and astrocytes in mouse cortical slices. To identify astrocytic involvement in acidosis-induced impairment, we induced the acidification in single GABAergic neuron by infusing proton intracellularly or in both neurons and astrocytes by using proton extracellularly. Compared the effects of intracellular acidification and extracellular acidification on GABAergic neurons, we found that their active intrinsic properties and synaptic outputs appeared more severely impaired in extracellular acidosis than intracellular acidosis. Meanwhile, extracellular acidosis deteriorated glutamate transporter currents on the astrocytes and upregulated excitatory synaptic transmission on the GABAergic neurons. Moreover, the antagonists of glutamate NMDA-/AMPA-receptors partially reverse extracellular acidosis-induced injury in the GABAergic neurons. Our studies suggest that acidosis leads to the dysfunction of cortical GABAergic neurons by astrocyte-mediated excitotoxicity, in addition to their metabolic changes as indicated previously.

  2. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

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    Jourdain, P.


    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  3. Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat. (United States)

    Wolf, Rainer; Dobrowolny, Henrik; Nullmeier, Sven; Bogerts, Bernhard; Schwegler, Herbert


    The role of the thalamus in schizophrenia has increasingly been studied in recent years. Deficits in the ventral thalamus have been described in only few postmortem and neuroimaging studies. We utilised our previously introduced neurodevelopmental animal model, the neonatal excitotoxic lesion of the ventral thalamus of Sprague-Dawley rats (Wolf et al., Pharmacopsychiatry 43:99-109, 22). At postnatal day (PD7), male pubs received bilateral thalamic infusions with ibotenic acid (IBA) or artificial cerebrospinal fluid (control). In adulthood, social interaction of two animals not familiar to each other was studied by a computerised video tracking system. This study displays clear lesion effects on social interaction of adult male rats. The significant reduction of total contact time and the significant increase in distance between the animals in the IBA group compared to controls can be interpreted as social withdrawal modelling a negative symptom of schizophrenia. The significant increase of total distance travelled in the IBA group can be hypothesised as agitation modelling a positive symptom of schizophrenia. Using a triple concept of social interaction, the percentage of no social interaction (Non-SI%) was significantly larger, and inversely, the percentage of passive social interaction (SI-passive%) was significantly smaller in the IBA group when compared to controls. In conclusion, on the background of findings in schizophrenic patients, the effects of neonatal ventral thalamic IBA lesions in adult male rats support the hypothesis of face and construct validity as animal model of schizophrenia.

  4. Intermittent hypoxia training: Powerful, non-invasive cerebroprotection against ethanol withdrawal excitotoxicity. (United States)

    Jung, Marianna E; Mallet, Robert T


    Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca 2+ loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence. Although the brain is heavily dependent on blood-borne O 2 to sustain its aerobic ATP production, brief, cyclic episodes of moderate hypoxia and reoxygenation, when judiciously applied over the course of days or weeks, evoke adaptations that protect the brain from ethanol withdrawal-induced glutamate excitotoxicity, mitochondrial damage, oxidative stress and amyloid β accumulation. This review summarizes evidence from ongoing preclinical research that demonstrates intermittent hypoxia training to be a potentially powerful yet non-invasive intervention capable of affording robust, sustained neuroprotection during ethanol withdrawal. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The Evaluation of the Effectiveness of Counterterrorism Policies on the PKK-inflicted Violence during the Democratization Process of Turkey

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    Irfan Ciftci


    Full Text Available This study tries to explore the relationship between soft-line governmental policy interventions of Turkey andthe responses of the PKK (The Kurdistan Workers’ Party by using time series data from 1995 to 2010. The negative binomial specifications for two models, the number of incidents and the number casualties are used. The aggregated impact of soft-line policies on the level of violence is found to be positive and significant. In one hand, Turkey’s EU accession process had a decreasing impact on PKK inflicted violence. On the other hand, the Active Repentance Law increased the violence in the short run. It was found that defiance based governmental policy interventions of Turkey had an increasing impact on the PKK-inflicted violence.

  6. Sex-related differences in childhood and adolescent self-inflicted injuries: a National Trauma Databank review. (United States)

    Branco, Bernardino Castelo; Inaba, Kenji; Barmparas, Galinos; Talving, Peep; David, Jean-Stephane; Plurad, David; Green, Donald J; Demetriades, Demetrios


    Recent reports have demonstrated increasing lethality among young women after inflicted injuries (SII). The aim of this study was to examine sex differences in the methods and outcomes of childhood and adolescent SII. The National Trauma Databank (v 7.0) was used to identify all patients 18 years or younger who sustained a SII. Demographic data, clinical data, and outcomes were compared between male and female patients. During the study period, a total of 1853 (61.1%) male and 1182 (38.9%) female patients sustained a SII. The most common SII mechanism in male patients was gunshot wound (32.1% vs 6.8%, P childhood and adolescence show distinct sex differences primarily with regard to mechanism. Males favor shooting; females, poisoning; younger ages, hanging. Gunshot wound and hanging were the 2 most lethal methods of self-inflicted injury. Copyright 2010 Elsevier Inc. All rights reserved.

  7. A 6-Year Case-Control Study of the Presentation and Clinical Sequelae for Noninflicted, Negligent, and Inflicted Pediatric Burns. (United States)

    Collier, Zachary J; Ramaiah, Veena; Glick, Jill C; Gottlieb, Lawrence J

    Inflicted burns are one of the leading causes of abuse-related fatalities in children. Between 30 and 60% of children accidentally returned to abusive homes suffer reabuse. Given the high chance for abuse recurrence and the associated morbidity/mortality, it is critical that inflicted burns are promptly identified to guide appropriate medical and child welfare management. Although previous studies proposed historical and mechanistic features using noncomparative or poorly powered data, this study utilized comparative data from a 6-year period (2009-2014) at a certified burn center along with expert analysis from Child Advocacy and Protective Services (CAPS) to provide higher level evidence supporting classical findings while elucidating new features with respect to burn severity and required interventions. A retrospective chart review of 408 pediatric burns was cross-referenced with the respective CAPS consultations to construct a multidisciplinary, deidentified database. The average age was 2.9 years (0.04-17 years) with 232 (57%) males and 330 (81%) African-Americans. CAPS investigations confirmed burn etiologies: noninflicted (346 [85%]), negligent (30 [7%]), and inflicted (32 [8%]). In comparing the three etiologies, statistical significance (P burn age, child welfare history, burn size and depth, distribution, concomitant injury rates, number of surgical interventions, infectious complications, and hospital length of stay. In addition to reaffirming classical features of abusive burns to fortify etiologic diagnoses, this study elucidated appreciable differences in burn severity, interventional sequelae, and burn-related complications, which will help guide medical and surgical interventions for future pediatric burn patients.

  8. Social interaction in young children with inflicted and accidental traumatic brain injury: relations with family resources and social outcomes. (United States)

    Ewing-Cobbs, Linda; Prasad, Mary R; Mendez, Donna; Barnes, Marcia A; Swank, Paul


    Core social interaction behaviors were examined in young children 0-36 months of age who were hospitalized for accidental (n = 61) or inflicted (n = 64) traumatic brain injury (TBI) in comparison to typically developing children (n = 60). Responding to and initiating gaze and joint attention (JA) were evaluated during a semi-structured sequence of social interactions between the child and an examiner at 2 and 12 months after injury. The accidental TBI group established gaze less often and had an initial deficit initiating JA that resolved by the follow-up. Contrary to expectation, children with inflicted TBI did not have lower rates of social engagement than other groups. Responding to JA was more strongly related than initiating JA to measures of injury severity and to later cognitive and social outcomes. Compared to complicated-mild/moderate TBI, severe TBI in young children was associated with less responsiveness in social interactions and less favorable caregiver ratings of communication and social behavior. JA response, family resources, and group interacted to predict outcomes. Children with inflicted TBI who were less socially responsive and had lower levels of family resources had the least favorable outcomes. Low social responsiveness after TBI may be an early marker for later cognitive and adaptive behavior difficulties.

  9. Experiences of self-blame and stigmatisation for self-infliction among individuals living with COPD. (United States)

    Halding, Anne-Grethe; Heggdal, Kristin; Wahl, Astrid


    Chronic obstructive pulmonary disease (COPD) is a major health problem estimated to become the third leading cause of death and the fifth leading cause of disability by 2020. Tobacco control is the most effective protective intervention, and it serves as a key element in patient counselling. However, a focus on tobacco control may cause unintended and adverse effects to individuals who already suffer from the disease. The current study aims to understand how patients with COPD experience daily life in a society with heavy emphasis on tobacco control. The design was longitudinal and descriptive. The sample included thirteen men and five women with COPD, recruited from pulmonary rehabilitation units. Data were collected by means of qualitative interviews and analysed using qualitative content analysis with search for meanings. The main theme was a feeling of being exiled in the world of the healthy, because of self-blame and society's stigmatisation of COPD as a self-inflicted disease. The participants experienced feelings of disgrace through subtle blame and a lack of support from their social network, health care encounters and larger society. This seemed to increase illness-related strain and a need for defensive actions. A small convenience sample, local cultural influence, the study's wide scope and lack of health professionals' views must be considered. This study illuminates the challenge of how to combine health advice on smoking cessation with nonblaming psycho-social support throughout the course of COPD. An awareness of the potential for stigma, the nature of nicotine dependence and broadened causal explanations for the disease may improve the ability of caregivers to address patient strain and its negative association with coping and well-being. Dilemmas in health communication concerning COPD patients' experience of stigma and negative emotional response should be further explored. © 2010 The Authors. Scandinavian Journal of Caring Sciences © 2010

  10. The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement. (United States)

    Kokona, Despina; Charalampopoulos, Ioannis; Pediaditakis, Iosif; Gravanis, Achille; Thermos, Kyriaki


    The aim of the present study was to investigate the neuroprotective properties of the endogenous neurosteroid dehydroepiandrosterone (DHEA) in an in vivo model of retinal excitotoxicity, and the involvement of Nerve Growth Factor (NGF) in its actions. Adult Sprague-Dawley rats (250-300 g) received intravitreally (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA; 42 nmol/eye) alone or in combination with DHEA (10(-8), 10(-7), 10(-6) M), or PBS (50 mM, control group). To examine the involvement of NGF and its TrkA receptor in the pharmacological effects of DHEA, animals received AMPA and NGF (60 pg/eye) in the absence or presence of a TrkA receptor inhibitor (Calbiochem 648450, 10(-6) M) or AMPA, DHEA (10(-6) M) and TrkA receptor inhibitor (10(-6), 10(-5) M). Immunohistochemistry studies [choline acetyltransferase (ChAT), brain nitric oxide synthetase (bNOS), calbindin, and TUNEL] and fluorescence-activated cell sorting (FACS) were used to examine retinal cell loss and protection. TrkA receptor immunoreactivity (-IR) and colocalization studies with relevant markers were also performed. AMPA (42 nmol) treatment resulted in a loss of bNOS, ChAT and calbindin immunoreactivities 24 h after its administration. DHEA, administered intravitreally, protected the retina from excitotoxicity in a dose-dependent manner. This effect was mimicked by NGF, and reversed by the NGF TrkA receptor inhibitor. The TrkA receptor is expressed in ganglion cells of rat retina. TUNEL staining and FACS analysis substantiated the neuroprotective actions of DHEA. These results demonstrate for the first time that the neurosteroid DHEA, administered intravitreally, protects the retina from AMPA excitotoxicity. An NGF TrkA receptor mechanism appears to be involved in this neuroprotection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. A beta-lactam antibiotic dampens excitotoxic inflammatory CNS damage in a mouse model of multiple sclerosis.

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    Nico Melzer

    Full Text Available In multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE, impairment of glial "Excitatory Amino Acid Transporters" (EAATs together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS. In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a beta-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in "Myelin Oligodendrocyte Glycoprotein" (MOG-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens. However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2. Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course. This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter. Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFgamma and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs e.g. dendritic cells (DCs and reduced T cell migration into the CNS in vivo. Taken together, we demonstrate, that a beta-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation. The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis.

  12. Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá


    be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were...... assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects...

  13. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis. (United States)

    Yan, Dingmin; Liu, Xishi; Guo, Sun-Wei


    One of major objectives in treating endometriosis is to alleviate pain since dysmenorrhea and other types of pain top the list of complaints from women with endometriosis who seek medical attention. Indeed, endometriosis-associated pain (EAP) is the most debilitating of the disease that negatively impacts on the quality of life in affected women, contributing significantly to the burden of disease and adding to the substantial personal and societal costs. Unfortunately, the mechanisms underlying the EAP are still poorly understood. In the last two decades, one active research field in endometriosis is the investigation on the distribution and genesis of nerve fibers in eutopic and ectopic endometrium, and the attempt to use endometrial nerve fiber density for diagnostic purpose. Since EAP presumably starts with the terminal sensory nerves, in or around endometriotic lesions, that transduce noxious mediators to the central nervous system (CNS) which ultimately perceives pain, this field of research holds the promise to elucidate the molecular mechanisms underlying the EAP, thus opening new avenues for novel diagnostics and therapeutics. In this review, we shall first briefly provide some basic facts on nerve fibers, and then provide an overview of some major findings in this filed while also note some conflicting results and expose areas in need of further research. We point out that since recently accumulated evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair, the relationship between endometriotic lesions and nerve fibers is not simply unidirectional, i.e. lesions promote hyperinnervations. Rather, it is bidirectional, i.e. endometriotic lesions and nerve fibers engage active cross-talks, resulting in the development of endometriosis and pain. That is, nerve fibers and endometriotic lesions are actually partners in crime in inflicting pains in women with endometriosis, aided and abetted possibly by other culprits

  14. Americans shooting themselves in the foot: the epidemiology of podiatric self-inflicted gunshot wounds in the United States. (United States)

    Cosco, Theodore D; King, James H


    To examine the epidemiology of Americans shooting themselves in the foot. Data from the Firearm Injury Surveillance Study (1993-2010) collected using the National Electronic Injury Surveillance System were examined. Non-fatal firearm-related injuries were recorded during patients' initial emergency department visits. United States hospital emergency departments, 1993-2010. 69 111 individuals admitted to US emergency departments after non-fatal firearm-related incidents. Demographic and incident characteristics of patients presenting with self-inflicted gunshot wounds to the foot. Of the 69 111 reported firearm-related injuries, 667 (1.0%) were self-inflicted gunshot wounds to the foot. Of these, 597 of the patients (89.6%) were men and 51.7% (345) were aged between 15 and 34 years. Patients generally presented with puncture wounds (265 patients, 39.7%), foreign bodies (164 patients, 24.6%) and bruised egos. Those who shot themselves in the foot were significantly more likely than individuals with other firearm-related injuries to be male (odds ratio [OR], 1.28) and married (OR, 2.6). As the festive season approached, the number of incidents increased; November and December were peak months for shooting oneself in the foot. The nature of and the circumstances surrounding self-inflicted gunshot wounds to the foot were unique when compared with other firearm-related injuries. Through the large-scale examination of the characteristics of these incidents, trends in the nature of Americans shooting themselves in the foot have been elucidated. Young married men are at particular risk of shooting themselves in the foot. Particular caution must be taken during the festive season to avoid being caught under the missing toe.

  15. Downregualtion of dynamin-related protein 1 attenuates glutamate-induced excitotoxicity via regulating mitochondrial function in a calcium dependent manner in HT22 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chi; Yuan, Xian-rui; Li, Hao-yu; Zhao, Zi-jin; Liao, Yi-wei; Wang, Xiang-yu; Su, Jun; Sang, Shu-shan; Liu, Qing, E-mail:


    Highlights: •Downregulation of Drp-1 attenuates glutamate-induced excitotoxicity. •Downregulation of Drp-1 inhibits glutamate-induced apoptosis. •Downregulation of Drp-1 reduces glutamate-induced mitochondrial dysfunction. •Downregulation of Drp-1 preserves intracellular calcium homeostasis. -- Abstract: Glutamate-mediated excitotoxicity is involved in many acute and chronic brain diseases. Dynamin related protein 1 (Drp-1), one of the GTPase family of proteins that regulate mitochondrial fission and fusion balance, is associated with apoptotic cell death in cancer and neurodegenerative diseases. Here we investigated the effect of downregulating Drp-1 on glutamate excitotoxicity-induced neuronal injury in HT22 cells. We found that downregulation of Drp-1 with specific small interfering RNA (siRNA) increased cell viability and inhibited lactate dehydrogenase (LDH) release after glutamate treatment. Downregulation of Drp-1 also inhibited an increase in the Bax/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Drp-1 siRNA transfection preserved the mitochondrial membrane potential (MMP), reduced cytochrome c release, enhanced ATP production, and partly prevented mitochondrial swelling. In addition, Drp-1 knockdown attenuated glutamate-induced increases of cytoplasmic and mitochondrial Ca{sup 2+}, and preserved the mitochondrial Ca{sup 2+} buffering capacity after excitotoxicity. Taken together, these results suggest that downregulation of Drp-1 protects HT22 cells against glutamate-induced excitatory damage, and this neuroprotection may be dependent at least in part on the preservation of mitochondrial function through regulating intracellular calcium homeostasis.

  16. VEGF receptor antagonist Cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult

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    McLarnon James G


    Full Text Available Abstract Background Excitotoxic brain insult is associated with extensive neuronal damage but could also cause inflammatory reactivity and vascular remodeling. The effects of the vascular endothelial growth factor (VEGF inhibitor, Cyclo-VEGI on expression of VEGF, microgliosis and astrogliosis, blood-brain barrier (BBB integrity and neuronal viability have been studied following intra-striatal injection of the excitotoxin, quinolinic acid (QUIN. The purpose of this study was to examine VEGF-dependent inflammatory responses in excitotoxin-injected brain and their dependence on pharmacological antagonism of VEGF receptors. Methods Single and double immunofluorescence staining of cellular (microglia, astrocyte, neuron responses and dye and protein infiltration of blood-brain barrier have been applied in the absence, and presence, of pharmacological modulation using a VEGF receptor antagonist, Cyclo-VEGI. Dunn-Bonferroni statistical analysis was used to measure for significance between animal groups. Results Detailed analysis, at a single time point of 1 d post-QUIN injection, showed excitotoxin-injected striatum to exhibit marked increases in microgliosis (ED1 marker, astrogliosis (GFAP marker and VEGF expression, compared with PBS injection. Single and double immunostaining demonstrated significant effects of Cyclo-VEGI treatment of QUIN-injected striatum to inhibit microgliosis (by 38%, ED1/VEGF (by 42% and VEGF striatal immunoreactivity (by 43%; astrogliosis and GFAP/VEGF were not significantly altered with Cyclo-VEGI treatment. Leakiness of BBB was indicated by infiltration of Evans blue dye and plasma protein fibrinogen into QUIN-injected striatum with barrier permeability restored by 62% (Evans blue permeability and 49% (fibrinogen permeability with Cyclo-VEGI application. QUIN-induced toxicity was demonstrated with loss of striatal neurons (NeuN marker and increased neuronal damage (Fluoro-Jade marker with significant neuroprotection

  17. Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17

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    Huang DS


    Full Text Available Ding-Siang Huang,1,* Hsuan-Yuan Lin,1,2,* Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li,1 Chung-Hsin Wu,1 Jung-Yaw Lin1,21Department of Life Science, National Taiwan Normal University, 2Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei City, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Spinocerebellar ataxia type 17 (SCA 17 is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.Keywords: spinocerebellar ataxia type 17, excitotoxicity, EGb 761, polyQ diseases, apoptosis 

  18. Novel application of stem cell-derived neurons to evaluate the time- and dose-dependent progression of excitotoxic injury.

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    Ian M Gut

    Full Text Available Glutamate receptor (GluR-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca(2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18, ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78-200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg(2+ or substitution of Ba(2+ for Ca(2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78-200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the

  19. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock. (United States)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M; Duggan, Michael; Sillesen, Martin; Deperalta, Danielle; Jepsen, Cecilie H; Lu, Jennifer; Li, Yongqing; deMoya, Marc A; Alam, Hasan B


    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this effect was owing to metabolic modulation. Yorkshire swine (n = 9) underwent a protocol of computer-controlled TBI and 40% hemorrhage and were resuscitated randomly with either fresh frozen plasma equal to the volume of shed blood (FFP; n = 4) or VPA (300 mg/kg) and FFP (FFP+VPA; n = 5). Hemodynamics, brain oxygenation, and blood glucose were monitored continuously for 6 hours after resuscitation. Cerebral microdialysis was used to measure glucose, lactate, pyruvate, glutamate, and glycerol levels at baseline, 1 and 2 hours post-shock, post-resuscitation (PR), and at 2, 4, and 6 hours PR. Brain samples from the injured side were then separated into mitochondrial and cytosolic fractions, and activity of pyruvate dehydrogenase complex (PDH) was measured using a dipstick assay kit. At baseline, there was no difference in brain lactate, pyruvate, glycerol, and glutamate concentrations between the groups. At all time points, there were no differences between the groups in brain oxygenation, cerebral perfusion pressure, or blood and brain glucose concentrations. After VPA infusion (PR time point), however, there was sustained decrease in lactate (0.91 ± 0.47 vs 2.54 ± 0.59 mmol/L; P glucose utilization for ATP production. There was also a decrease in concentrations of glutamate (6.64 ± 3.68 vs 42.25 ± 27.07 mmol/L; P = .02) and glycerol (19.20 ± 6.76 vs 69.75 ± 30.07 mmol/L; P = .01), in the FFP+VPA group, signifying lesser degree of excitotoxicity and brain damage, respectively. Brain PDH activity was greater in the mitochondrial fractions (5,984 ± 504 adjusted volume intensity [INT] × mm(2) vs 4,332 ± 1,055 INT × mm(2); P = .04) and lower in cytosolic fractions in the FFP

  20. Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation (United States)

    Rivero-Segura, Nadia A.; Flores-Soto, Edgar; García de la Cadena, Selene; Coronado-Mares, Isabel; Gomez-Verjan, Juan C.; Ferreira, Diana G.; Cabrera-Reyes, Erika Alejandra; Lopes, Luísa V.; Massieu, Lourdes


    Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca2+] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca2+]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases. PMID:28475602

  1. Protection of neurons in the retinal ganglion cell layer against excitotoxicity by the N-acylethanolamine, N-linoleoylethanolamine

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    Duncan RS


    Full Text Available R. Scott Duncan1,*, Hua Xin1,*, Daryl L Goad1, Kent D Chapman2,3, Peter Koulen1,31Vision Research Center and Departments of Ophthalmology and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, MO, USA; 2Department of Biological Sciences, University of North Texas, Denton, TX, USA; 3Center for Plant Lipid Research, University of North Texas, Denton, TX, USA *Authors contributed equallyAbstract: Retinal ganglion cell (RGC death is a hallmark of neurodegenerative diseases and disease processes of the eye, including glaucoma. The protection of RGCs has been an important strategy for combating glaucoma, but little clinical success has been reported to date. One pathophysiological consequence of glaucoma is excessive extracellular glutamate subsequently leading to excitotoxicity in the retina. Endocannabinoids, such as the N-acylethanolamine (NAE, arachidonylethanolamine (NAE 20:4, exhibit neuroprotective properties in some models of neurodegenerative disease. The majority of NAEs, however, are not cannabinoids, and their physiological function is not clear. Here, we determined whether the noncannabinoid NAE, linoleoylethanolamine (NAE18:2, protects neurons in the RGC layer against glutamate excitotoxicity in ex-vivo retina cultures. Using a terminal deoxynucleotidyl transferase-mediated dUTP (2´-deoxyuridine 5´-triphosphate nick-end labeling (TUNEL assay, we determined that NAE18:2 reduces the number of apoptotic RGC layer neurons in response to glutamate and conclude that NAE18:2 is a neuroprotective compound with potential for treating glaucomatous retinopathy.Keywords: neuroprotection, glutamate, calcium signaling, immunocytochemistry, eye, vision, glaucoma.

  2. Excitotoxic insult results in a long-lasting activation of CaMKIIα and mitochondrial damage in living hippocampal neurons.

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    Nikolai Otmakhov

    Full Text Available Over-activation of excitatory NMDA receptors and the resulting Ca2+ overload is the main cause of neuronal toxicity during stroke. CaMKII becomes misregulated during such events. Biochemical studies show either a dramatic loss of CaMKII activity or its persistent autonomous activation after stroke, with both of these processes being implicated in cell toxicity. To complement the biochemical data, we monitored CaMKII activation in living hippocampal neurons in slice cultures using high spatial/temporal resolution two-photon imaging of the CaMKIIα FRET sensor, Camui. CaMKII activation state was estimated by measuring Camui fluorescence lifetime. Short NMDA insult resulted in Camui activation followed by a redistribution of its protein localization: an increase in spines, a decrease in dendritic shafts, and concentration into numerous clusters in the cell soma. Camui activation was either persistent (> 1-3 hours or transient (~20 min and, in general, correlated with its protein redistribution. After longer NMDA insult, however, Camui redistribution persisted longer than its activation, suggesting distinct regulation/phases of these processes. Mutational and pharmacological analysis suggested that persistent Camui activation was due to prolonged Ca2+ elevation, with little impact of autonomous states produced by T286 autophosphorylation and/or by C280/M281 oxidation. Cell injury was monitored using expressible mitochondrial marker mito-dsRed. Shortly after Camui activation and clustering, NMDA treatment resulted in mitochondrial swelling, with persistence of the swelling temporarily linked to the persistence of Camui activation. The results suggest that in living neurons excitotoxic insult produces long-lasting Ca2+-dependent active state of CaMKII temporarily linked to cell injury. CaMKII function, however, is to be restricted due to strong clustering. The study provides the first characterization of CaMKII activation dynamics in living neurons

  3. The endocannabinoid N-arachidonoyldopamine (NADA) exerts neuroprotective effects after excitotoxic neuronal damage via cannabinoid receptor 1 (CB(1)). (United States)

    Grabiec, Urszula; Koch, Marco; Kallendrusch, Sonja; Kraft, Robert; Hill, Kerstin; Merkwitz, Claudia; Ghadban, Chalid; Lutz, Beat; Straiker, Alex; Dehghani, Faramarz


    Endocannabinoids exert numerous effects in the CNS under physiological and pathological conditions. The aim of the present study was to examine whether the endocannabinoid N-arachidonoyldopamine (NADA) may protect neurons in excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). OHSC were excitotoxically lesioned by application of N-methyl-d-aspartate (NMDA, 50 μM) for 4 h and subsequently treated with different NADA concentrations (0.1 pM-50 μM) alone or in combination with cannabinoid receptor antagonists. NADA protected dentate gyrus granule cells and caused a slight reduction in the number of microglial cells. The number of degenerated neurons significantly decreased between 100 pM and 10 μM NADA (p NADA mediated neuroprotection, we applied the cannabinoid (CB) receptor 1 (CB(1)) inverse agonist/antagonist AM251, CB(2) inverse agonist/antagonist AM630, abnormal-cannabidiol (abn-CBD)-sensitive receptor antagonist O-1918, transient receptor potential channel V1 (TRPV1) antagonist 6-iodonordihydrocapsaicin and A1 (TRPA1) antagonist HC-030031. Neuroprotective properties of low (1 nM) but not high (10 μM) NADA concentrations were solely blocked by AM251 and were absent in CB(1)(-/-) mice. AM630, O-1918, 6-iodonordihydrocapsaicin and HC-030031 showed no effects at all NADA concentrations applied. Our findings demonstrate that NADA protects dentate gyrus granule cells by acting via CB(1). NADA reduced the number of microglial cells at distinct concentrations. TRPV1 and TRPA1 were not involved in NADA mediated neuroprotection. Thus, our data implicate that NADA mediated activation of neuronal CB(1) may serve as a novel pharmacological target to mitigate symptoms of neuronal damage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. [The possibilities for the expert diagnostics of the influence of the glance of a bullet on the character of the injuries inflicted by shooting a hunting weapon]. (United States)

    Makarov, I Yu; Galkina, A M; Kinle, A F; Fetisov, V A


    The objective of the present work was to study and analyze the available data concerning the influence of the glance of a bullet on the character of the injuries inflicted by shooting certain types of hunting weapons. This review gives evidence of the possibility of the objective diagnostics of the injuries inflicted by gunshots using the rifle-bore weapons. However, we have failed to find information about the diagnostic criteria for the evaluation of the wounds inflicted by the bullets shot from smooth-bore hunting rifles after their glance from various surfaces in the available special literature publications. Such situation creates the prerequisites for the erroneous conclusions from the results of forensic medical expertise of the after-penetration blunt wounds.

  5. The association of alcohol drinking pattern and self-inflicted intentional injury in Korea: a cross-sectional WHO collaborative emergency room study. (United States)

    Chun, Sungsoo; Reid, Easton A; Yun, Mieun


    Self-inflicted intentional injuries are increasing at an alarming rate in the Republic of Korea, yet few reports describe their relationship with alcohol consumption. The aim of this study was to characterise the association of alcohol drinking patterns and self-inflicted intentional injury in Korean emergency departments (EDs) using WHO collaborative study protocol. Cross-sectional study. Data were collected from four general hospital EDs in four geographically diverse regions of Korea: Seoul, Suwon, Chuncheon and Gwangju. Information was collected on 1989 patients aged 18 and above. A representative probability sample was drawn from patients admitted to each ED for the first time within 6 h of injury. Alcohol-related non-fatal injuries. Among 467 persons with alcohol-related injuries, 33 (7.1%), were self-inflicted intentional injuries and 137 (29.3%) were intentional injuries caused by someone else. The adjusted odds of self-inflicted intentional injury verses unintentional injury were calculated for heavy (OR 1.764; 95% CI 0.783 to 3.976), binge (OR 2.125; 95% CI 0.930 to 4.858) and moderate drinking (OR 3.039; 95% CI 1.129 to 8.178) after controlling for demographic variables. Similar odds were reported for pooled intentional injury data (self-inflicted and caused by someone else) and drinking patterns. These data show a strong association between all patterns of acute alcohol consumption and self-inflicted intentional injury in the Republic of Korea.

  6. A review of stab wound injuries at a tertiary trauma centre in Singapore: are self-inflicted ones less severe? (United States)

    Leow, Jeffrey J; Lingam, Pravin; Lim, Vanessa W; Go, Karen TS; Chiu, Ming Terk; Teo, Li Tserng


    INTRODUCTION In Singapore, as strict laws are a strong deterrent against armed violence, little is known about the epidemiology of penetrating stab wound injuries. Our study aimed to investigate the epidemiology of stab wound injuries at a major trauma centre in Singapore and determine if there was a difference in severity between self-inflicted stab wound (SI) injuries and those inflicted by others (IO). METHODS We retrospectively reviewed all penetrating injuries at Tan Tock Seng Hospital, and identified and categorised all stab wound injuries as SI or IO. Basic demographic information, injury severity characteristics and outcome data were compared between these two groups. A review of all mortalities was performed, including recording the causes of death. RESULTS Between 2005 and 2010, there were a total of 149 stab wound injuries, of which 24 (16.1%) were SI and 125 (83.9%) were IO injuries. Patients tended to be young (mean age 34.1 ± 14.2 years). The mean Injury Severity Score was significantly different between the SI and IO groups (8.8 ± 6.5 vs. 12.3 ± 8.1; p = 0.03). In both groups, the majority underwent an operative procedure (83.3% vs. 85.6%) and had an average hospital stay of four days. CONCLUSION The study confirms our hypothesis that SI injuries tend to be less severe than IO injuries and are more likely to occur at home rather than at a public area. This finding may be useful in the triage of patients with stab wound injuries. PMID:26831311

  7. Blasphemy As Violence: Trying to Understand the Kind of Injury That Can Be Inflicted by Acts and Artefacts That Are Construed As Blasphemy

    NARCIS (Netherlands)

    Baumgartner, C.|info:eu-repo/dai/nl/304835250


    This article suggests an understanding of blasphemy as violence that enables us to identify various kinds of injury that can be inflicted by blasphemous acts and artefacts. Understanding blasphemy as violence can take three forms: physical violence, indirect intersubjective violence, and

  8. Self-Inflicted Lesions in Dermatology: A Management and Therapeutic Approach - A Position Paper From the European Society for Dermatology and Psychiatry

    NARCIS (Netherlands)

    Tomas-Aragones, Lucia; Consoli, Silla M.; Consoli, Sylvie G.; Poot, Francoise; Taube, Klaus-Michael; Linder, M. Dennis; Jemec, Gregor B. E.; Szepietowski, Jacek C.; de Korte, John; Lvov, Andrey; Gieler, Uwe


    The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new

  9. nNOS(+ striatal neurons, a subpopulation spared in Huntington Disease, possess functional NMDA receptors but fail to generate mitochondrial ROS in response to an excitotoxic challenge

    Directory of Open Access Journals (Sweden)

    Lorella M.T. Canzoniero


    Full Text Available Hungtinton’s disease (HD is a neurodegenerative condition characterized by severe neuronal loss in the cortex and striatum that leads to motor and behavioral deficits. Excitotoxicity is thought to be involved in HD and several studies have indicated that NMDA receptor (NMDAR overactivation can play a role in the selective neuronal loss found in HD. Interestingly, a small subset of striatal neurons (less than 1% of the overall population is found to be spared in post-mortem HD brains. These neurons are medium-sized aspiny interneurons that highly express the neuronal isoform of nitric oxide synthase (nNOS. Intriguingly, nNOS(+ neurons show reduced vulnerability to NMDAR-mediated excitotoxicity. Mechanisms underlying this reduced vulnerability are still largely unknown. One untested possibility is that nNOS(+ neurons possess fewer or less functioning NMDARs. Employing single cell calcium imaging we challenged this hypothesis and found that cultured striatal nNOS(+ neurons show NMDAR-evoked responses that are identical to the ones observed in the overall population of nNOS(- neurons. NMDAR-dependent dysregulation of intraneuronal Ca2+ is known to generate high levels of reactive oxygen species of mitochondrial origin (mt-ROS, a crucial step in the excitotoxic cascade. With confocal imaging and dihydrorhodamine (DHR; a ROS-sensitive probe we compared mt-ROS levels generated by NMDAR activation in nNOS(+ and (- striatal neurons. DHR experiments revealed that nNOS(+ neurons failed to produce significant amounts of mt-ROS in response to NMDA exposure, thereby providing a mechanism for their reduced vulnerability to excitotoxicity.

  10. Brain ischaemia induces shedding of a BDNF-scavenger ectodomain from TrkB receptors by excitotoxicity activation of metalloproteinases and γ-secretases. (United States)

    Tejeda, Gonzalo S; Ayuso-Dolado, Sara; Arbeteta, Raquel; Esteban-Ortega, Gema M; Vidaurre, Oscar G; Díaz-Guerra, Margarita


    Stroke remains a leading cause of death and disability in the world with limited therapies available to restrict brain damage or improve functional recovery after cerebral ischaemia. A promising strategy currently under investigation is the promotion of brain-derived neurotrophic factor (BDNF) signalling through tropomyosin-related kinase B (TrkB) receptors, a pathway essential for neuronal survival and function. However, TrkB and BDNF-signalling are impaired by excitotoxicity, a primary pathological process in stroke also associated with neurodegenerative diseases. Pathological imbalance of TrkB isoforms is critical in neurodegeneration and is caused by calpain processing of BDNF high affinity full-length receptor (TrkB-FL) and an inversion of the transcriptional pattern of the Ntrk2 gene, to favour expression of the truncated isoform TrkB-T1 over TrkB-FL. We report here that both TrkB-FL and neuronal TrkB-T1 also undergo ectodomain shedding by metalloproteinases activated after ischaemic injury or excitotoxic damage of cortical neurons. Subsequently, the remaining membrane-bound C-terminal fragments (CTFs) are cleaved by γ-secretases within the transmembrane region, releasing their intracellular domains (ICDs) into the cytosol. Therefore, we identify TrkB-FL and TrkB-T1 as new substrates of regulated intramembrane proteolysis (RIP), a mechanism that highly contributes to TrkB-T1 regulation in ischaemia but is minor for TrkB-FL which is mainly processed by calpain. However, since the secreted TrkB ectodomain acts as a BDNF scavenger and significantly alters BDNF/TrkB signalling, the mechanism of RIP could contribute to neuronal death in excitotoxicity. These results are highly relevant since they reveal new targets for the rational design of therapies to treat stroke and other pathologies with an excitotoxic component. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia. (United States)

    Wagner, Amy K; Bayir, Hülya; Ren, Dianxu; Puccio, Ava; Zafonte, Ross D; Kochanek, Patrick M


    Excitotoxicity and ischemia can result in oxidative stress after TBI. Female sex hormones are hypothesized to be neuroprotective after TBI by affecting multiple mechanisms of secondary injury, including oxidative damage, excitotoxicity and ischemia. Ca2+ mediated oxidative stress increases with age, and hypothermia is known to attenuate secondary injury. The purpose of this study was to determine if the relationship between cerebral spinal fluid (CSF) markers of excitotoxicity, ischemia, and oxidative damage are gender and age specific and the role of hypothermia in affecting these relationships. F2-isoprostane, glutamate, and lactate/pyruvate, were assessed in CSF from adults (n = 68) with severe TBI (Glasgow coma scale [GCS] score gender effect (p gender*time interaction (p = 0.012) on F2-isoprostane/glutamate ratios. A significant gender effect (p = 0.050) and gender*time interaction (p = 0.049) was also seen with F2-isoprostane/lactate/pyruvate. Hypothermia (p = 0.001) and age (p = 0.026) significantly increased F2-isoprostane/glutamate ratios. Females had a significant inverse relationship between day 1 F2-isoprostane/glutamate ratios and GOS scores (r =- 0.43; p = 0.05) as well as day 1 F2-isoprostane/lactate/pyruvate ratio (r =- 0.46; p = 0.04) and GOS scores. These results indicate that females have smaller oxidative damage loads than males for a given excitotoxic or ischemic insult and female gonadal hormones may play a role in mediating this neuroprotective effect. These results also suggest that susceptibility to glutamate mediated oxidative damage increases with age and that hypothermia differentially attenuates CSF glutamate versus F2-isoprostane production. Gender and age differences in TBI pathophysiology should be considered when conducting clinical trials in TBI.

  12. NMDA Receptor-Mediated Neuroprotective Effect of the Scutellaria baicalensis Georgi Extract on the Excitotoxic Neuronal Cell Death in Primary Rat Cortical Cell Cultures

    Directory of Open Access Journals (Sweden)

    Jinsong Yang


    Full Text Available The objective of the current research work was to evaluate the neuroprotective effect of the ethanol extract of Scutellaria baicalensis (S.B. on the excitotoxic neuronal cell death in primary rat cortical cell cultures. The inhibitory effects of the extract were qualitatively and quantitatively estimated by phase-contrast microscopy and lactate dehydrogenase (LDH assays. The extract exhibited a potent and dose-dependent inhibition of the glutamate-induced excitotoxicity in the culture media. Further, using radioligand binding assays, it was observed that the inhibitory effect of the extract was more potent and selective for the N-methyl-D-aspartate (NMDA receptor-mediated toxicity. The S.B. ethanol extract competed with [3H] MDL 105,519 for the specific binding to the NMDA receptor glycine site with 50% inhibition occurring at 35.1 μg/mL. Further, NMDA receptor inactivation by the S.B. ethanol extract was concluded from the decreasing binding capability of [3H]MK-801 in the presence of the extract. Thus, S.B. extract exhibited neuroprotection against excitotoxic cell death, and this neuroprotection was mediated through the inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor. Phytochemical analysis of the bioactive extract revealed the presence of six phytochemical constituents including baicalein, baicalin, wogonin, wogonoside, scutellarin, and Oroxylin A.

  13. Survivors of self-inflicted gunshot wounds to the head: characterization of ocular injuries and health care costs. (United States)

    Reddy, Amit K; Baker, Meredith S; Sobel, Rachel K; Whelan, David A; Carter, Keith D; Allen, Richard C


    Suicides and attempted suicides are major public health issues in the United States and around the world. Self-inflicted gunshot wounds (SIGSWs) are a common method of attempting suicide, the head being the most commonly injured body region; however, the literature lacks an overview of the orbital and ocular injuries as well as outcomes associated with SIGSWs. To characterize the ocular and orbital injuries and outcomes of patients presenting with SIGSWs and to examine the cost associated with these injuries. Retrospective medical record review was performed of all patients who presented to the University of Iowa Hospitals and Clinics between 2003 to 2013 with the admitting diagnosis of self-inflicted injuries via firearms. Patients with no periorbital or ocular injuries and/or those who did not survive for at least 2 months following the incident were excluded. Ocular injuries and outcomes and health care costs and reimbursements, which were generated by a financial report obtained from the hospital finance department that included data from both the hospital billing and cost accounting systems. All patients in this study (n = 18) were men with a mean age of 47.2 years. Eight patients (44.4%) displayed submental missile entry points, 7 (38.9%) displayed intraoral entry points, and 3 (16.7%) displayed pericranial entry points. Patients with pericranial entries sustained more severe ocular injuries and had poorer ocular outcomes. Seven patients (38.9%) were found at final follow-up to have visual acuity of 20/40 or better in each eye and all showed missile trajectories in the sagittal plane. The mean cost of treatment of these patients totaled $117,338 while the mean reimbursement amount was $124,388. Data regarding ocular injuries and outcomes may assist ophthalmologists in the treatment of patients with SIGSWs in the future. Many patients had extremely functional vision at final follow-ups, which highlights the importance of specialists conducting examinations

  14. Heavy metal injection as an unusual self-infliction; Schwermetall-Inkorporation als ungewoehnliche Selbst(be)schaedigung

    Energy Technology Data Exchange (ETDEWEB)

    Kernbach-Wighton, G.; Kijewski, H.; Sprung, R.; Saternus, K.S. [Goettingen Univ. (Germany). Inst. fuer Rechtsmedizin; Degner, D. [Goettingen Univ. (Germany). Klinik fuer Psychosomatik und Psychotherapie; Riegel, A. [Goettingen Univ. (Germany). Abt. Roentgendiagnostik III - Neuroradiologie


    A 19-year-old man was admitted to hospital because of uncharacteristic neurologic symptoms. During the first examination morphologic alterations due to an injection of mercury into the left arm and the left side of the trunk were found. The dose and the manner of application were doubtful and suspected to be a case of self-infliction. The man informed the police only 7 months later because his relatives had finally persuaded him to do so. The description of the infliction by unknown perpetrators was full of contradictions. Initially the patient gave only an indistinct description. But later on, the number of details increased. At the same time there was a change in the characteristics of the perpetrator(s). Other differences existed concerning a loss of consciousness which should have been caused by a single stroke on an arm. Furthermore, the patient told about a swelling as big as an egg, provoked by an injection of liquid mercury. It could be shown by experiments that mercury can be injected into soft-tissue very simply and that it spread widely. Arguments for a self-injection were e.g. the technical possibility, the topography of the injection marks, and an easy handling of the syringe. A psychiatric examination furthermore revealed, that the patient had had periods of restriction of thinking, sometimes combined with a lack of appreciation. (orig.) [Deutsch] Ein 19jaehriger Mann wurde wegen uncharakteristischer neurologischer Symtome klinisch aufgenommen. Anlaesslich der Aufnahmeuntersuchung wurde ein Z.n. Quecksilberinjektion im Bereich des linken Armes und des Rumpfes diagnostiziert. Fraglich waren Dosis, Beibringungsart sowie Fremd- oder Selbstbeibringung. Eine polizeiliche Anzeige nach 7 Monaten erfolgte auf Draengen von Verwandten. Die Darstellung einer Fremdbeibringung war in sich widerspruechlich. Z.B. bestand zuerst eine schemenhafte Tatschilderung bei einem allmaehlich zunehmenden Detailreichtum sowie gleichzeitig wechselnden Personenmerkmalen

  15. Withanone, an Active Constituent from Withania somnifera, Affords Protection Against NMDA-Induced Excitotoxicity in Neuron-Like Cells. (United States)

    Dar, Nawab John; Bhat, Javeed Ahmad; Satti, Naresh Kumar; Sharma, Parduman Raj; Hamid, Abid; Ahmad, Muzamil


    Withania somnifera has immense pharmacologic and clinical uses. Owing to its similar pharmacologic activity as that of Korean Ginseng tea, it is popularly called as Indian ginseng. In most cases, extracts of this plant have been evaluated against various diseases or models of disease. However, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to evaluate Withanone, one of the active constituents of Withania somnifera against NMDA-induced excitotoxicity in retinoic acid, differentiated Neuro2a cells. Cells were pre-treated with 5, 10 and 20 μM doses of Withanone and then exposed to 3-mM NMDA for 1 h. MK801, a specific NMDA receptor antagonist, was used as positive control. The results indicated that NMDA induces significant death of cells by accumulation of intracellular Ca2+, generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, crashing of Bax/Bcl-2 ratio, release of cytochrome c, increased caspase expression, induction of lipid peroxidation as measured by malondialdehyde levels and cleavage of poly(ADP-ribose) polymerase-1 (Parp-1), which is indicative of DNA damage. All these parameters were attenuated with various doses of Withanone pre-treatment. These results suggest that Withanone may serve as potential neuroprotective agent.

  16. Neuroprotective effects of Rhodiola rosea extracts against excitotoxicity and oxygen-glucose deprivation in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Sindberg, Jeanne; Lundberg, Louise

    . rosea roots (Clone 5, Pharmaplant, Germany, grown for four years) as well as chemical fractions and/or purified compounds (e.g. salidrosid, rosavin) against excitotoxicity and ischemia-like brain damage using organotypic hippocampal slice cultures. Hippocampal slice cultures derived from 8 days old rat...... pups were grown for 2-3 weeks before exposure to N-methyl-D-aspartate (NMDA, 10 µM, 24 h) or oxygen-glucose deprivation (OGD, 30 or 35 min), with and without presence of R. rosea extracts or compounds during and 24 h after the insult. NMDA- or OGD-induced neuronal cell death was monitored...... and quantified by propidium iodide uptake and immunohistochemical staining for MAP2 as a neuronal marker. Significant and dose-dependent protection against NMDA and OGD-induced CA1 pyramidal cell death was obtained by crude extracts using 250 µg/ml (33-50% protection) or 500 µg/ml (45-65% protection). A number...

  17. Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice. (United States)

    Uribe, Valeria; Wong, Bibiana K Y; Graham, Rona K; Cusack, Corey L; Skotte, Niels H; Pouladi, Mahmoud A; Xie, Yuanyun; Feinberg, Konstantin; Ou, Yimiao; Ouyang, Yingbin; Deng, Yu; Franciosi, Sonia; Bissada, Nagat; Spreeuw, Amanda; Zhang, Weining; Ehrnhoefer, Dagmar E; Vaid, Kuljeet; Miller, Freda D; Deshmukh, Mohanish; Howland, David; Hayden, Michael R


    Apoptosis, or programmed cell death, is a cellular pathway involved in normal cell turnover, developmental tissue remodeling, embryonic development, cellular homeostasis maintenance and chemical-induced cell death. Caspases are a family of intracellular proteases that play a key role in apoptosis. Aberrant activation of caspases has been implicated in human diseases. In particular, numerous findings implicate Caspase-6 (Casp6) in neurodegenerative diseases, including Alzheimer disease (AD) and Huntington disease (HD), highlighting the need for a deeper understanding of Casp6 biology and its role in brain development. The use of targeted caspase-deficient mice has been instrumental for studying the involvement of caspases in apoptosis. The goal of this study was to perform an in-depth neuroanatomical and behavioral characterization of constitutive Casp6-deficient (Casp6-/-) mice in order to understand the physiological function of Casp6 in brain development, structure and function. We demonstrate that Casp6-/- neurons are protected against excitotoxicity, nerve growth factor deprivation and myelin-induced axonal degeneration. Furthermore, Casp6-deficient mice show an age-dependent increase in cortical and striatal volume. In addition, these mice show a hypoactive phenotype and display learning deficits. The age-dependent behavioral and region-specific neuroanatomical changes observed in the Casp6-/- mice suggest that Casp6 deficiency has a more pronounced effect in brain regions that are involved in neurodegenerative diseases, such as the striatum in HD and the cortex in AD.

  18. Made up by makeup--A case report about an exceptional kind of self-inflicted "injuries". (United States)

    Mauf, Sabrina; Martinez, Rosa M; Thali, Michael J; Bartsch, Christine


    Self-inflicted injuries are a known, but challenging topic in the healthcare sector and the judicial system. Therefore, differentiation of these injuries from a third-party-interference is crucial in the field of forensic medicine. However, self-painted injuries with makeup, which entail misleading of medical staff and the administration of justice, have apparently not been described in the literature so far. A case of a rare kind of victim role staging in a 26-year-old Caucasian woman in the field of forensic medicine is presented. She supposedly had been robbed and harmed by two unknown men. The forensic examination revealed subjective symptoms and objective findings, such as skin discolorations appearing as fresh bruises. However, a closer look revealed makeup. After removal, no injuries were seen. Awareness of the existence of exceptional cases of victim role staging is essential in the daily routine of healthcare, judicial and forensic professionals. Therefore, a questioning attitude within the physical examination as well as proper assessment of objective findings is crucial. Furthermore, the importance of an interdisciplinary approach of possible factitious disorders is demonstrated. The sensitization may exclude a third-party-interference, prevent damages to the health care system, avoid misleading of the administration of justice, and, therefore, reduce socioeconomic costs. Moreover, the recognition may enable adequate interventions and provide patients with professional help. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. [The forensic medical characteristic of the factors associated with a shot from the 9.0 mm pneumatic rifle and the inflicted injuries]. (United States)

    Raĭzberg, S A; Makarov, I Iu; Lorents, A S


    The objective of the present work was to elucidate the structural characteristics of the 9.0 mm pneumatic rifle and three regular types of the bullets differing in the head shape fired from it. Morphological features of the injuries inflicted by such bullets are described in conjunction with the peculiarities of precipitation of the shot products in their projection as the prerequisites for their objective differentiation. Results: The study allowed to reveal the composition of the gunshot residues and to determine the maximum distance of their distribution. The specific features of experimental damage inflicted by the shots from the 9.0 mm pneumatic rifle to the coarse white calico fabric targets were shown to depend on the shot range. The objective signs of the so-called "short-range" shot from the 9.0 mm pneumatic rifle were described for the first time.

  20. Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of α7 nicotinic receptors and internalization of NMDA receptors (United States)

    Shen, H; Kihara, T; Hongo, H; Wu, X; Kem, WR; Shimohama, S; Akaike, A; Niidome, T; Sugimoto, H


    BACKGROUND AND PURPOSE Glutamate excitotoxicity may be involved in ischaemic injury to the CNS and some neurodegenerative diseases, such as Alzheimer's disease. Donepezil, an acetylcholinesterase (AChE) inhibitor, exerts neuroprotective effects. Here we demonstrated a novel mechanism underlying the neuroprotection induced by donepezil. EXPERIMENTAL APPROACH Cell damage in primary rat neuron cultures was quantified by lactate dehydrogenase release. Morphological changes associated with neuroprotective effects of nicotine and AChE inhibitors were assessed by immunostaining. Cell surface levels of the glutamate receptor sub-units, NR1 and NR2A, were analyzed using biotinylation. Immunoblot was used to measure protein levels of cleaved caspase-3, total NR1, total NR2A and phosphorylated NR1. Immunoprecipitation was used to measure association of NR1 with the post-synaptic protein, PSD-95. Intracellular Ca2+ concentrations were measured with fura 2-acetoxymethylester. Caspase 3-like activity was measured using enzyme substrate, 7-amino-4-methylcoumarin (AMC)-DEVD. KEY RESULTS Levels of NR1, a core subunit of the NMDA receptor, on the cell surface were significantly reduced by donepexzil. In addition, glutamate-mediated Ca2+ entry was significantly attenuated by donepezil. Methyllycaconitine, an inhibitor of α7 nicotinic acetylcholine receptors (nAChR), inhibited the donepezil-induced attenuation of glutamate-mediated Ca2+ entry. LY294002, a phosphatidyl inositol 3-kinase (PI3K) inhibitor, had no effect on attenuation of glutamate-mediated Ca2+ entry induced by donepezil. CONCLUSIONS AND IMPLICATIONS Decreased glutamate toxicity through down-regulation of NMDA receptors, following stimulation of α7 nAChRs, could be another mechanism underlying neuroprotection by donepezil, in addition to up-regulating the PI3K-Akt cascade or defensive system. PMID:20718745

  1. Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model. (United States)

    Edwards, Adam B; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P


    In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1-6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

  2. Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats. (United States)

    Chang, Chia Ying; Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Ying Chou; Chou, Shang Shing Peter; Wang, Su Jane


    The citrus flavonoid hesperidin exerts neuroprotective effects and could cross the blood-brain barrier. Given the involvement of glutamate neurotoxicity in the pathogenesis of neurodegenerative disorders, this study was conducted to evaluate the potential role of hesperidin in glutamate release and glutamate neurotoxicity in the hippocampus of rats. In rat hippocampal nerve terminals (synaptosomes), hesperidin inhibited the release of glutamate and elevation of cytosolic free Ca(2+) concentration evoked by 4-aminopyridine (4-AP), but did not alter 4-AP-mediated depolarization. The inhibitory effect of hesperidin on evoked glutamate release was prevented by chelating the extracellular Ca(2+) ions and blocking the activity of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels or protein kinase C. In hippocampal slice preparations, whole-cell patch clamp experiments showed that hesperidin reduced the frequency of spontaneous excitatory postsynaptic currents without affecting their amplitude, indicating the involvement of a presynaptic mechanism. In addition, intraperitoneal (i.p.) injection of kainic acid (KA, 15 mg/kg) elevated the extracellular glutamate levels and caused considerable neuronal loss in the hippocampal CA3 area. These KA-induced alterations were attenuated by pretreatment with hesperidin (10 or 50 mg/kg, i.p.) before administering the KA. These results demonstrate that hesperidin inhibits evoked glutamate release in vitro and attenuates in vivo KA-induced neuronal death in the hippocampus. Our findings indicate that hesperidin may be a promising candidate for preventing or treating glutamate excitotoxicity related brain disorders such as neurodegenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Association between violence against women inflicted by the partner and chronic malnutrition in their children under five years old in Peru]. (United States)

    Ruiz-Grosso, Paulo; Loret de Mola, Christian; Miranda, J Jaime


    To assess the association between violence against women inflicted by their partner and the prevalence of chronic malnutrition in their children less than five years old. A secondary cross-sectional analysis of the 2001 Peru Demographic and Health Survey performed in Peru, with national representativeness. The dependent variable was chronic malnutrition in the youngest child under five years old. The independent variables were emotional violence, physical violence (mild or severe) and sexual violence self-report; the violence was inflicted by the mother's last partner or spouse in the last 12 months. Univariate and multivariate analysis was performed, generalized linear models (log-binomial regression) were used, and the nature of the sample was taken into account. Models for socio-demographic and mother-son health variables were adjusted. Prevalence ratios (PR) and confidence intervals were calculated. Data from 5,154 mothers and children were analyzed. The prevalence of chronic malnutrition was 19.8% (CI 95%: 18.1-21.6). In the multivariate analysis, a higher prevalence of chronic malnutrition was found in the children whose mothers had a history of severe physical violence history: PR=1.27% (IC 95%: 1.09-1.48). There was no evidence of association between the prevalence of chronic malnutrition and other kinds of violence inflicted by a partner. The mothers' report of physical violence in the last year was associated with an increased prevalence of chronic malnutrition in children under five years old.

  4. Aprotinin, but not ε-aminocaproic acid and tranexamic acid, exerts neuroprotection against excitotoxic injury in an in vitro neuronal cell culture model. (United States)

    Lu, Zhaohui; Korotcova, Ludmila; Murata, Akira; Ishibashi, Nobuyuki; Jonas, Richard A


    Lack of availability of aprotinin has resulted in increased clinical use of the alternative antifibrinolytic agents, ε-aminocaproic acid (EACA) and tranexamic acid (TXA), which are known to be associated with an increased risk of seizures. In contrast, aprotinin has previously been demonstrated to be neuroprotective through suppression of excitotoxicity-mediated neuronal degeneration via the extracellular plasminogen/plasmin system. This study compares the effect of antifibrinolytic agents on neuronal and mixed glial/neuronal cell cultures. Mixed cortical cultures containing neuronal and glial cells were prepared from fetal mice and plated on a layer of confluent astrocytes from postnatal pups. A primary neuronal culture was obtained from the same gestational stage and plated in multiwall vessels. Slowly triggered excitotoxicity was induced by 24-hour exposure to 12.5 mM N-methyl-D-aspartate (NMDA). Apoptotic neuronal cell death was induced by exposure of primary neural cultures to 24 hours of serum deprivation. Compared with NMDA alone, no significant changes in cell death were observed for any dose of TXA or EACA in mixed cultures. Conversely, a clinical dose of aprotinin significantly reduced cell death by -31% on average. Aprotinin reduced apoptotic neuronal cell death from 75% to 37.3%, and to 34.1% at concentrations of 100 and 200 kIU/mL, respectively, and significantly decreased neuronal nuclear damage. These concentrations of aprotinin significantly inhibited caspase 9 and 3/7 activations; 250 kIU/mL aprotinin exerted maximal protection on primary cortical neurons. In contrast to aprotinin, EACA and TXA exert no protective effect against excitotoxic neuronal injury that can occur during cardiac surgery. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  5. Kinin-B2 receptor mediated neuroprotection after NMDA excitotoxicity is reversed in the presence of kinin-B1 receptor agonists.

    Directory of Open Access Journals (Sweden)

    Antonio H Martins

    Full Text Available BACKGROUND: Kinins, with bradykinin and des-Arg(9-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg(9-bradykinin as well as Lys-des-Arg(9-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-D-aspartate (NMDA-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. PRINCIPAL FINDINGS: Bradykinin at 10 nM and 1 µM concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg(9-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059, showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. CONCLUSIONS: Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg(9

  6. Adenosine A2B receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity

    Directory of Open Access Journals (Sweden)

    Moidunny Shamsudheen


    Adenosine from glutamate-stressed neurons induces rapid LIF release in astrocytes. This rapid release of LIF promotes the survival of cortical neurons against excitotoxicity.

  7. Involvement of superoxide in excitotoxicity and DNA fragmentation in striatal vulnerability in mice after treatment with the mitochondrial toxin, 3-nitropropionic acid. (United States)

    Kim, Gyung W; Chan, Pak H


    Oxidative stress and excitotoxicity have been implicated in selective striatal vulnerability caused by the mitochondrial toxin, 3-nitropropionic acid (3-NP), which may simulate Huntington's disease in animals and humans. The detailed mechanism of the role of superoxide in striatal vulnerability induced by 3-NP is still unknown. The authors investigated oxidative cellular injury and DNA fragmentation after systemic 3-NP injection in wild-type (Wt) mice and mutant mice with a deficiency in manganese superoxide dismutase (MnSOD; Sod2 -/+). Furthermore, they investigated the effects of decortication after 3-NP treatment in Sod2 -/+ mice, and copper/zinc SOD (CuZnSOD) treatment in recently developed Sod2 -/+ mice that overexpress CuZnSOD (SOD1 +/- / Sod2 -/+ mice). Oxidized hydroethidine, 8-hydroxyguanosine immunoreactivity, and nitrotyrosine immunoreactivity were increased in the Sod2 -/+ mice compared with the Wt mice after 3-NP treatment (P Decortication completely abolished oxidative striatal damage after 3-NP treatment in the Sod2 -/+ mice. Increased CuZnSOD attenuated DNA fragmentation and striatal lesion volume after 3-NP treatment in the Sod2 -/+ mice (P < 0.001). These data suggest that production of superoxide may be a critical step to excitotoxicity and subsequent DNA fragmentation in selective striatal vulnerability after 3-NP treatment.

  8. The Zinc Ion Chelating Agent TPEN Attenuates Neuronal Death/apoptosis Caused by Hypoxia/ischemia Via Mediating the Pathophysiological Cascade Including Excitotoxicity, Oxidative Stress, and Inflammation. (United States)

    Wang, Wei-Ming; Liu, Zhao; Liu, Ai-Jun; Wang, Yu-Xiang; Wang, Hong-Gang; An, Di; Heng, Bin; Xie, Lai-Hua; Duan, Jun-Li; Liu, Yan-Qiang


    We aim to determine the significant effect of TPEN, a Zn(2+) chelator, in mediating the pathophysiological cascade in neuron death/apoptosis induced by hypoxia/ischemia. We conducted both in vivo and in vitro experiments in this study. PC12 cells were used to establish hypoxia/ischemia model by applying oxygen-glucose deprivation (OGD). SHR-SP rats were used to establish an acute ischemic model by electrocoagulating middle cerebral artery occlusion. The effect of TPEN on neuron death/apoptosis was evaluated. In addition, the relative biomarks of excitotoxicity, oxidative stress, and inflammation reactions in hypoxia/ischemia PC12 cell model as well as in SHR-SP rat hypoxia/ischemia model were also assessed. TPEN significantly attenuates the neurological deficit, reduced the cerebral infarction area and the ratio of apoptotic neurons, and increased the expression of GluR2 in the rat hypoxia/ischemia brain. TPEN also increased blood SOD activity, decreased blood NOS activity and blood MDA and IL-6 contents in rats under hypoxia/ischemia. In addition, TPEN significantly inhibited the death and apoptosis of cells and attenuated the alteration of GluR2 and NR2 expression caused by OGD or OGD plus high Zn(2+) treatments. Zn(2+) is involved in neural cell apoptosis and/or death caused by hypoxia/ischemia via mediating excitotoxicity, oxidative stress, and inflammation. © 2015 John Wiley & Sons Ltd.

  9. The use of organotypic hippocampal slice cultures to evaluate protection by non-competitive NMDA receptor antagonists against excitotoxicity

    DEFF Research Database (Denmark)

    Ring, Avi; Tanso, Rita; Noraberg, Jens


    There is a wide interest in testing neuroprotectants which inhibit the neurodegeneration that results from excessive activation of brain NMDA receptors.  As an alternative to in vivo testing in animal models we demonstrate here the use of a complex in vitro model to compare the efficacy...... with in vivo tests in rodents . We conclude that the slice culture model provides valuable pre-clinical data and applying the model to screen neuroprotectants may significantly limit the use of in vivo tests in animals....... blockers that inhibit excitotoxic injury and their neuroprotective capacity have been extensively investigated in vivo in animal models. They have also been evaluated as potential countermeasure agents against organophosphate poisoning. Quantitative densitometric image analysis of propidium iodide uptake...

  10. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.

    Directory of Open Access Journals (Sweden)

    Caridad Galindo-Romero

    Full Text Available We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina.

  11. Anti-excitotoxic effects of cannabidiol are partly mediated by enhancement of NCX2 and NCX3 expression in animal model of cerebral ischemia. (United States)

    Khaksar, Sepideh; Bigdeli, Mohammad Reza


    Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death. Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in the neurodegenerative diseases studies. The present investigation was designed to determine whether cannabidiol can alleviate the severity of ischemic damages and if it is able to exert its anti-excitotoxic effects through sodium and calcium regulation. By using stereotaxic surgery, a guide cannula was implanted into the lateral ventricle. Cannabidiol (50, 100, and 200ng/rat; i.c.v.) was administrated for 5 consecutive days. After pretreatment, the rats were subjected to 60min of right middle cerebral artery occlusion (MCAO). After 24h, neurological deficits score, infarct volume, brain edema, and blood-brain barrier (BBB) permeability in total of hemisphere, cortex, piriform cortex-amygdala, and striatum were assessed. The expression of Na + /Ca 2+ exchangers (NCXs) protein as an endogenous target in these regions was also studied. The present results indicate that administration of cannabidiol (100 and 200ng/rat) in the MCAO-induced cerebral ischemia caused a remarkable reduction in neurological deficit, infarction, brain edema, and BBB permeability in comparison with the vehicle group. Up-regulation of NCX2 and NCX3 in cannabidiol-received groups was also observed. These findings support the view that the reduction of ischemic injuries elicited by cannabidiol can be at least partly due to the enhancement of NCX protein expression and its cerebro-protective role in those cerebral territories supplied by MCA. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Excitotoxicity Induced by Realgar in the Rat Hippocampus: the Involvement of Learning Memory Injury, Dysfunction of Glutamate Metabolism and NMDA Receptors. (United States)

    Huo, Tao-guang; Li, Wei-kai; Zhang, Ying-hua; Yuan, Jie; Gao, Lan-yue; Yuan, Yuan; Yang, Hui-lei; Jiang, Hong; Sun, Gui-fan


    Realgar is a type of mineral drug containing arsenic. The nervous system toxicity of realgar has received extensive attention. However, the underlying mechanisms of realgar-induced neurotoxicity have not been clearly elucidated. To explore the mechanisms that contribute to realgar-induced neurotoxicity, weanling rats were exposed to realgar (0, 0.3, 0.9, 2.7 g/kg) for 6 weeks, and cognitive ability was tested using the Morris water maze (MWM) test and object recognition task (ORT). The levels of arsenic in the blood and hippocampus were monitored. The ultrastructures of hippocampal neurons were observed. The levels of glutamate (Glu) and glutamine (Gln) in the hippocampus and hippocampal CA1 region; the activities of glutamine synthetase (GS) and phosphate-activated glutaminase (PAG); the mRNA and protein expression of glutamate transporter 1 (GLT-1), glutamate/aspartate transporter (GLAST), and N-methyl-D-aspartate (NMDA) receptors; and the level of intracellular Ca(2+) were also investigated. The results indicate that the rats developed deficiencies in cognitive ability after a 6-week exposure to realgar. The arsenic contained in realgar and the arsenic metabolites passed through the blood-brain barrier (BBB) and accumulated in the hippocampus, which resulted in the excessive accumulation of Glu in the extracellular space. The excessive accumulation of Glu in the extracellular space induced excitotoxicity, which was shown by enhanced GS and PAG activities, inhibition of GLT-1 mRNA and protein expression, alterations in NMDA receptor mRNA and protein expression, disturbance of intracellular Ca(2+) homeostasis, and ultrastructural changes in hippocampal neurons. In conclusion, the findings from our study indicate that exposure to realgar induces excitotoxicity and that the mechanism by which this occurs may be associated with disturbances in Glu metabolism and transportation and alterations in NMDA receptor expression.

  13. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina. (United States)

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Hallböök, Finn


    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina.

  14. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Wang Yi


    Full Text Available Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. Results We created transgenic mice that express the coral (Discosoma sp. red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS mice expressing human mutant superoxide dismutase-1. Conclusions These novel transgenic mice will be a useful tool for better understanding

  15. Folic Acid Protects Against Glutamate-Induced Excitotoxicity in Hippocampal Slices Through a Mechanism that Implicates Inhibition of GSK-3β and iNOS. (United States)

    Budni, Josiane; Molz, Simone; Dal-Cim, Tharine; Martín-de-Saavedra, Maria Dolores; Egea, Javier; Lopéz, Manuela G; Tasca, Carla Ines; Rodrigues, Ana Lúcia Severo


    Folic acid (folate) is a vitamin of the B-complex group crucial for neurological function. Considering that excitotoxicity and cell death induced by glutamate are involved in many disorders, the potential protective effect of folic acid on glutamate-induced cell damage in rat hippocampal slices and the possible intracellular signaling pathway involved in such effect were investigated. The treatment of hippocampal slices with folic acid (100 μM) significantly abrogated glutamate (1 mM)-induced reduction of cell viability measured by MTT reduction assay and inhibited glutamate-induced D-[(3)H]-aspartate release. To investigate the putative intracellular signaling pathways implicated in the protective effect of folic acid, we used a PI3K inhibitor, LY294002, which abolished the protective effects of folic acid against glutamate-induced cell damage and D-[(3)H] aspartate release. Moreover, hippocampal slices incubated with folic acid alone for 30 min presented increased phosphorylation of GSK-3β at Ser9, indicating an inhibition of the activity of this enzyme. Furthermore, folic acid in the presence of glutamate insult in hippocampal slices maintained for an additional period of 6 h in fresh culture medium without glutamate and/or folic acid induced phosphorylation of GSK-3β and β-catenin expression. In addition, glutamate-treated hippocampal slices showed increased iNOS expression that was reversed by folic acid. In conclusion, the results of this study show that the protective effect of folic acid against glutamate-induced excitotoxicity may involve the modulation of PI3K/GSK-3β/β-catenin pathway and iNOS inhibition.

  16. [The specific features of the damage to the non-biological and biological simulators of the human body inflicted by the shots from a 9.0 mm pneumatic rifle]. (United States)

    Rajzberg, S A; Makarov, I Ju; Lorents, A S


    The objective of the present work was to study the specific constructional features of a 9.0 mm pneumatic rifle designed to use three types of bullets differing in the head shape. Also, the morphological signs of the injuries inflicted by such bullets that can serve as the prerequisites for objective differentiation of the damages are considered. The study revealed peculiarities of experimental damage to the non-biological (plasticine blocks) and biological (bio-mannequins) simulators of homogeneous human tissues inflicted by the shots from the pneumatic rifle from different distances.

  17. Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: A review of current work. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Ledney, G.D.; Madonna, G.S.; Elliott, T.B.; Moore, M.M.; Jackson, W.E.


    When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, the authors developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60 (Co sources). Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections.

  18. Cathepsin L plays a role in quinolinic acid-induced NF-Κb activation and excitotoxicity in rat striatal neurons.

    Directory of Open Access Journals (Sweden)

    Yan-Ru Wang

    Full Text Available The present study seeks to investigate the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-κB activation and excitotoxicity in rats striatal neurons. Stereotaxic administration of the N-methyl-d-aspartate (NMDA receptor agonist Quinolinic acid (QA into the unilateral striatum was used to produce the in vivo excitotoxic model. Co-administration of QA and the cathepsin L inhibitor Z-FF-FMK or 1-Naphthalenesulfonyl-IW-CHO (NaphthaCHO was used to assess the contribution of cathepsin L to QA-induced striatal neuron death. Western blot analysis and cathepsin L activity assay were used to assess the changes in the levels of cathepsin L after QA treatment. Western blot analysis was used to assess the changes in the protein levels of inhibitor of NF-κB alpha isoform (IκB-α and phospho-IκB alpha (p-IκBα after QA treatment. Immunohistochemical analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced NF-κB. Western blot analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced IκB-α phosphorylation and degradation, changes in the levels of IKKα, p-IKKα, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced loss of striatal neurons were strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced degradation of IκB-α, NF-κB nuclear translocation, up-regulation of NF-κB responsive gene TP53, and activation of caspase-3 was strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced increases in beclin 1, LC3II/LC3I, and down-regulation of p62 were reduced by Z-FF-FMK or NaphthaCHO. These results suggest that cathepsin L is involved in glutamate receptor-induced NF-κB activation. Cathepsin L inhibitors have neuroprotective effects by inhibiting glutamate receptor-induced IκB-α degradation and NF-κB activation.

  19. Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Diana L Price


    Full Text Available Dementia with Lewy bodies (DLB and Parkinson's Disease (PD are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn. Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR, particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the

  20. [The foreign experience with the application of the modern radiodiagnostic methods for the estimation of prescription of death coming and time of infliction of injury]. (United States)

    Fetisov, V A; Kuprina, T A; Sinitsyn, V E; Dubrova, S E; Filimonov, B A


    We undertook the analysis of the foreign publications concerning the application of the modern radiodiagnostic methods (including MSCT- and MRI-visualization) with reference to the solution of the traditional problems facing forensic medical expertise, such as the estimation of prescription of death coming and time of infliction of injury in the dead bodies. Both advantages and disadvantages of postmortem visualization of the corpses of adult subjects are discussed taking into consideration the period of time that elapsed between the death and the onset of the study as well as the character of the injuries. It was shown that the examination of the corpses using the up-to-date methods of radiodiagnostics prior to autopsy makes it possible for morphologists, jointly with radiologists, to identify, to see in the new light, and to evaluate the number of charges in the dead body, such as the alteration of the blood cell sedimentation rate, the formation of postmortem hypostases in the internal organs, the hardening of the walls of aorta and major blood vessels, right heart dilatation, gradual smoothing of the borderline between grey and white matter of the brain. Virtual autopsy can be useful , even for the study of such long-term processes in the corpses as putrefaction, saponification, mummification, and peat tanning. Moreover, this technique may be instrumental in the elucidation of the specific features of topographic-anatomical relationships between individual 'tissues and organs, detection of the concealed lesions, and a variety of pathological changes. Postmortem visualization allows for the quantitative evaluation of the severity of these transformations and the preliminary estimation of prescription of death coming. Also, radiodiagnostic methods can be employed to reliably visualize and measure various hemorrhagic events (from the density of such ones as liquid and clotted blood) in the tissues surrounding the fractures, in body cavities, and internal organs as

  1. Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB. (United States)

    Wang, Rui; Li, Ying-Bo; Li, Yu-Hua; Xu, Ying; Wu, Hong-Li; Li, Xue-Jun


    Curcumin is a major active component isolated from Curcuma longa. Previously, we have reported its significant antidepressant effect. However, the mechanisms underlying the antidepressant effects are still obscure. In the present study, we explored the effect of curcumin against glutamate excitotoxicity, mainly focusing on the neuroprotective effects of curcumin on the expression of Brain-Derived Neurotrophic Factor (BDNF), which is deeply involved in the etiology and treatment of depression. Exposure of rat cortical neurons to 10 microM glutamate for 24 h caused a significant decrease in BDNF level, accompanied with reduced cell viability and enhanced cell apoptosis. Pretreatment of neurons with curcumin reversed the BDNF expression and cell viability in a dose- and time-dependent manner. However, K252a, a Trk receptor inhibitor which is known to inhibit the activity of BDNF, could block the survival-promoting effect of curcumin. In addition, the up-regulation of BDNF levels by curcumin was also suppressed by K252a. Taken together, these results suggest that the neuroprotective effect of curcumin might be mediated via BDNF/TrkB signaling pathway.

  2. Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: the role of the infralimbic cortex in context generalisation.

    Directory of Open Access Journals (Sweden)

    Rachel eAshwell


    Full Text Available The prelimbic and infralimbic regions of the rat medial prefrontal cortex (mPFC are important components of the limbic cortico-striatal circuit, receiving converging projections from the hippocampus (HPC and amygdala. Mounting evidence points to these regions having opposing roles in the regulation of the expression of contextual fear and context-induced cocaine-seeking. To investigate this functional differentiation in motivated behaviour further, this study employed a novel radial maze task previously shown to be dependent on the integrity of the hippocampus and its functional connection to the nucleus accumbens shell, to investigate the effects of selective excitotoxic lesions of the PL and IL upon the spatial contextual control over reward learning. To this end, rats were trained to develop discriminative responding towards a reward-associated discrete cue presented in three out of six spatial locations (3 arms out of 6 radial maze arms, and to avoid the same discrete cue presented in the other 3 spatial locations. Once acquired, the reward contingencies of the spatial locations were reversed, such that responding to the cue presented in a previously rewarded location is no longer rewarded. Furthermore, the acquisition of spatial learning was probed separately using conditioned place preference and the monitoring of arm selection at the beginning of each training session. Lesions of the PL transiently attenuated the acquisition of the initial cue approach training and spatial learning, while leaving reversal learning intact. In contrast, IL lesions led to a significantly superior performance of spatial context-dependent discriminative cue approach and reversal learning, in the absence of a significant preference for the new reward-associated spatial locations. These results indicate that the PL and IL have functionally dissociative, and potentially opposite roles in the regulation of spatial contextual control over appetitive learning.

  3. The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. (United States)

    Gleeson, Lorna C; Ryan, Katie J; Griffin, Eadaoin W; Connor, Thomas J; Harkin, Andrew


    Excitotoxicity is a mechanism of neuronal cell death implicated in a range of neurodegenerative conditions. Systemic administration of the excitotoxin kainic acid (KA) induces inflammation and apoptosis in the hippocampus, resulting in neuronal loss. Evidence indicates that stimulation of glial β(2)-adrenoceptors has anti-inflammatory and neurotrophic properties that could result in neuroprotection. Consequently, in this study we examined the effect of the β(2)-adrenoceptor agonist clenbuterol on KA-induced inflammation, neurotrophic factor expression and apoptosis in the hippocampus. Clenbuterol (0.5mg/kg) was administered to rats one hour prior to KA (10mg/kg). Epileptic behaviour induced by KA was assessed for three hours following administration using the Racine scale. Twenty-four hours later TUNEL staining in the CA3 hippocampal subfield and hippocampal caspase-3 activity was assessed to measure KA-induced apoptosis. In addition, expression of inflammatory cytokines (IL-1β and IFN-γ), inducible nitric oxide synthase (iNOS), kynurenine pathway enzymes indolamine 2,3-dioxygenase (IDO) and kynurenine monooxygenase (KMO), the microglial activation marker CD11b, and the neurotrophins BDNF and NGF were quantified in the hippocampus using real-time PCR. Whilst clenbuterol treatment did not significantly alter KA-induced epileptic behavior it ameliorated KA-induced apoptosis, and this neuroprotective effect was accompanied by reduced inflammatory cytokine expression, reduced expression of iNOS, IDO, KMO and CD11b, coupled with increased BDNF and NGF expression in KA-treated rats. In conclusion, the β(2)-adrenoceptor agonist clenbuterol has anti-inflammatory and neurotrophic actions and elicits a neuroprotective effect in the KA model of neurodegeneration. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. (United States)

    Yu, Lijian; Zhang, Yongping; Ma, Rundi; Bao, Li; Fang, Juanzhi; Yu, Tingxi


    The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain. [(3)H]-labeled glutamate was used as radiotracer to study the effect of ferulic acid on distribution of MSG in mouse fetal brain. MSG dissolved in distilled water (2.0 g/kg body weight, 640 kBq of [(3)H]glutamate/mouse, ig) or/and sodium ferulate (SF) (20, 40, 80 mg/kg body weight, ip), was given to pregnant mice at 17-19 days; the distribution of [(3)H] glutamate in the mouse fetal brains was measured at 30, 60, 90, 120 min after administration of MSG or/and SF. Maternal mice were given MSG (1.0, 2.0, 4.0 g/kg body weight, ig) or/and SF (20, 40, 80 mg/kg body weight, ip) simultaneously at 17-19 days of pregnancy, and then behavioral tests and histopathological observations were used to analyze glutamate-induced functional and morphological changes of the brains of their offspring, and Western blot analysis was performed for examining expressions of bcl-2 and caspase-3. The results showed that SF obviously inhibited the uptake of labeled glutamate in fetal brain. In addition, SF countered the effects of MSG on behavior, histopathology, genetic toxicity, and expression of apoptosis-related gene. The results suggest that ferulic acid is a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist and neuroprotector. In conclusion, maternal administration of ferulic acid has potent protective effects against glutamate-induced neurotoxicity in their filial mice.

  5. Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion. (United States)

    Inui, Keiko; Hanafusa, Takaaki; Namiki, Takeshi; Ueno, Makiko; Igawa, Ken; Yokozeki, Hiroo


    A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, al-though the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC) therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

  6. Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion

    Directory of Open Access Journals (Sweden)

    Keiko Inui


    Full Text Available A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, although the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

  7. Self-inflicted skin lesions

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Smith, Matthias Nybro; Jemec, Gregor B E


    professionals, the European Society for Dermatology and Psychiatry (ESDaP) recently proposed a classification of psychodermatological terms in order to establish a coherent use of terms across the medical fields involved. We reviewed current and previous psychodermatological diagnoses in order to clarify how...

  8. [Do the glutamate excitotoxicity theory and potential free radicals implication in schizophrenia aetiopathogenesis provide a new enlightenment to links between: genome, environment and biology in the determinism of that disorder?]. (United States)

    Nguimfack Mbodie, P C


    The aetiopathogenesis of schizophrenia constitutes nowadays one of the major points of interest for researchers on this cosmopolitan disorder which involves about 1% of the world population and which significantly alters the social functioning of the individual. Numerous studies have focused on the role played by genome, environmental factors and biology in the development of symptoms. The neurodevelopmental theory is an illustration with the perinatal period considered as the main provider of environmental factors (hypertension, infections, bleedings during pregnancy, acute and chronic fetal distress.). Many authors found significant associations between such factors, the occurrence of brain lesions and finally schizophrenic symptoms. Although no convincing genetic model had been established to date for schizophrenia, nevertheless it appears that a predisposition not inheritable under the mendelian mode exists and authors showed that disease gets more and more severe over schizophrenic descendants. The risk to be schizophrenic being a first degree relative of the schizophrenic person is about ten time superior than in general population. Indeed, this risk is also about ten time superior in biological parents of schizophrenic adoptees than in biological parents of healthy adoptees. Studies done in monozygotic comparing to dizygotic twins are in favour of an important role played by genetic factors more than socioeducational or psychological factors. Concerning biology, the dopaminergic hypothesis remains shared by numerous authors although direct links with incriminated factors are not well established. Now is suspected the glutamate excitotoxicity with implication of free radicals in schizophrenia. These free radicals are products of various enzymatic activations led by overstimulation of post synaptic receptors (NMDA and AMPA) by the excess glutamate. Therefore, according to that concept, some amino acids as glutamate and derivatives could have through free

  9. Anti-GQ1b ganglioside positive Miller Fisher syndrome - evidence of paranodal pathology on nerve biopsy. (United States)

    Miller, James A L; Spyropoulos, Achillefs; Jaros, Evelyn; Galban-Horcajo, Francesc; Whittaker, Roger G; Willison, Hugh J


    Miller Fisher syndrome is a regional variant of Guillain-Barre syndrome with a characteristic clinical triad of ophthalmoplegia, areflexia and ataxia and occasionally distal limb sensory loss. 90% of patients have associated antibodies to the GQ1b ganglioside. The pathophysiology of antibody-mediated peripheral nerve impairment remains uncertain. This report includes the first description of a peripheral sensory nerve biopsy in Miller Fisher syndrome. A single case report is described of a 46 year old woman who presented with 2 weeks of distal glove and stocking sensory loss to both deep and superficial sensory modalities, areflexia and weight loss. This was followed by rapid onset of ataxia, ophthalmoplegia, and bulbar impairment. Peripheral neurophysiology showed reduced sensory nerve amplitudes with preserved conduction velocities in keeping with an axonal pattern of impairment. Clinical concerns of a systemic inflammatory disorder led to a diagnostic peripheral nerve biopsy from the sensory branch of the radial nerve. However she subsequently made a complete recovery over 5 weeks. Combinatorial glycoarrays confirmed restricted serum binding for GQ1b in acute serum which later resolved in a convalescent sample. The nerve biopsy showed lengthening of nodes of Ranvier, myelin splitting and macrophage internodal axonal invasion without any features of demyelination. The pathological features were strikingly similar to those found in acute motor axonal neuropathy and indicate the region of the node of Ranvier to be a primary focus of GQ1b induced damage in Miller Fisher syndrome, at least in this particular overlap syndrome with prominent sensory nerve involvement.


    African Journals Online (AJOL)



    Jul 1, 2017 ... This means that despite the fact that families in these rural communities have, for long, been impoverished, the continuity of the Khomba practice is almost guaranteed. Community perceptions on the impact of khombaon child well-being. Khomba perceived as a part of child socialization and preservation of ...

  11. Self-inflicted transparietal intraventricular nail: case report and ...

    African Journals Online (AJOL)

    Background Deliberate self-harm with stone- or hammer-driven nail through the cranium is unusual. The need is stressed for comprehensive radiological evaluation with computed tomography (CT) scan, with or without angiography, and removal through an open cranial procedure under general anaesthesia, rather than ...

  12. Self-inflicted bilateral orchidectomy precipitated by erotic bizarre ...

    African Journals Online (AJOL)

    Aboseif et al observed psychotic patients were at risk of repeating their acts of self mutilation as occurred in this patient.7 Deliberate self- harm patients can be non-compliant and difficult to engage in therapy.8 Crawford and Wessely noted that willingness of patients to engage with interventions, following DSH, is a key issue ...

  13. FastStats: Self-Inflicted Injury/Suicide (United States)

    ... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... States, 1999-2014 Suicide Rates for Females and Males by Race/Ethnicity: United States: 1999 and 2014 [ ...

  14. The Self-Inflicted Irrelevance of American Academics. (United States)

    Wacquant, Loic J. D.


    Anti-intellectualism and negative public attitudes about the professoriate are traced to four sources: (1) unquestioned supremacy of economic over cultural capital in the United States; (2) lack of organizational vehicles for faculty to contribute to social change and public debate; (3) unfair competition from policy institutes and foundations;…

  15. Creative deaminases, self-inflicted damage, and genome evolution. (United States)

    Conticello, Silvestro G


    Organisms minimize genetic damage through complex pathways of DNA repair. Yet a gene family--the AID/APOBECs--has evolved in vertebrates with the sole purpose of producing targeted damage in DNA/RNA molecules through cytosine deamination. They likely originated from deaminases involved in A>I editing in tRNAs. AID, the archetypal AID/APOBEC, is the trigger of the somatic diversification processes of the antibody genes. Its homologs may have been associated with the immune system even before the evolution of the antibody genes. The APOBEC3s, arising from duplication of AID, are involved in the restriction of exogenous/endogenous threats such as retroviruses and mobile elements. Another family member, APOBEC1, has (re)acquired the ability to target RNA while maintaining its ability to act on DNA. The AID/APOBECs have shaped the evolution of vertebrate genomes, but their ability to mutate nucleic acids is a double-edged sword: AID is a key player in lymphoproliferative diseases by triggering mutations and chromosomal translocations in B cells, and there is increasing evidence suggesting that other AID/APOBECs could be involved in cancer development as well. © 2012 New York Academy of Sciences.

  16. genetics and inheritance of seed dormancy inflicted by seed

    African Journals Online (AJOL)


    reference to its genetic factors. Bull. Inst. Res. Tohoku University 14:1-. 879 (J). Takahashi T 1997 Inheritance of seed germination and dormancy. In. Science of the Rice Plant Genetics. Vol. 3. Eds. T Matsao et al (1997). FAO Policy Center, Tokyo. Tomar JB 1984 Genetics of grain dormancy in rice (Oryza sativa L.) Genetica.

  17. Self-inflicted injury: An attempt of autoglossectomy !!!

    Directory of Open Access Journals (Sweden)

    S V Ravindra


    Full Text Available Teeth are considered as strongest, functional and unique organs of the body. In some situations, they act as injurious agents especially among the individuals with psychotic state. Oral self-mutilation is generally a diagnostic challenge for practitioners, since the incidence of oral self-mutilation in routine dental setups is uncommon. So, here we report a case of autoglossectomy in a 19-year-old male with behavioral problem.

  18. Vitrification of bovine blastocysts produced in vitro inflicts selective damage to the inner cell mass. (United States)

    Gómez, E; Muñoz, M; Rodríguez, A; Caamaño, J N; Facal, N; Díez, C


    In contrast to the embryos derived from live animals, the embryos produced in vitro undergo increased damage and reduced survival after cryopreservation, particularly when produced with serum. In medium containing serum, retinoic acid increases cell numbers in the inner cell mass and the trophectoderm without altering their relative proportions in the bovine blastocyst. In this work, in medium without serum, we analyzed the contribution of retinoic acid to the development of blastocyst and survival to vitrification, and found a strong cell reduction in the inner mass when compared to the trophectoderm. Day-6 in vitro-produced morulae were treated for 24 h with retinoic acid (0.7 and 1.4 microm) and subsequently cultured without additives for a further 24 h period. Day-8 blastocyst production and cell counts in hatched blastocysts were unaffected by retinoic acid. However, Day-7 expanded, vitrified embryos produced with retinoic acid 1.4 microm survived at lower rates than controls when cultured after warming. Vitrification greatly reduced cell numbers in the inner mass (p vitro survival to cryopreservation is sometimes scarcely informative on the viability of the embryo after transfer to recipients.

  19. Self-inflicted testicular amputation in first lysergic acid diethylamide use. (United States)

    Blacha, Christian; Schmid, Markus M; Gahr, Maximilian; Freudenmann, Roland W; Plener, Paul L; Finter, Florian; Connemann, Bernhard J; Schönfeldt-Lecuona, Carlos


    Genital self-mutilation is a well-known phenomenon in patients with schizophrenia and has occasionally been described in patients with personality disorders or transsexuality. However, literature just provides few cases of genital self-mutilation related to the use of psychotropic substances. A previously mentally healthy man (age, 32 years) performed manual amputation of both testes after first use of lysergic acid diethylamide in combination with alcohol consumption. Follow-up examination 6 month after the event did not reveal the development of a psychiatric disorder. This report shows that a first and single use of lysergic acid diethylamide in combination with alcohol can cause intoxication with dramatic consequences.

  20. Bone marrow edema induced by a bullet after a self-inflicted accidental firing. (United States)

    Berger, Nicole; Paula, Pia; Gascho, Dominic; Flach, Patricia M; Thali, Michael J; Ross, Steffen G; Ampanozi, Garyfalia


    We present a case of a postmortem finding of bone marrow edema in postmortem magnetic resonance imaging (PMMR) indirectly induced by a bullet, which barely missed the bone of a 92-year-old man found kneeling in front of his bed of a tidy apartment. Additionally, a selective postmortem computed tomography angiography (PMCTA) of the left leg was performed, visualizing a laceration of the left femoral vein by the bullet with consecutive contrast media extravasation. A vast pulmonary fat embolism was diagnosed and together with the blood loss found to be the cause of death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Self-Inflicted Wounds: Debates and Divisions within al-Qa’ida and its Periphery (United States)


    known for his independent, and sometimes blunt, criticism of the extremism of global  jihadi doctrines, tactics and  modus   operandi . He wrote at‐Qa’ida. His document was  serialized  in fifteen parts in al‐Masri al‐Yaoum, an Egyptian newspaper, between 18 November and 26  December 2007.  54...tarnish the  image of the  jihadists in the media, portraying them as bloodthirsty  killers  of innocent  people:  I say to you: that we are in a battle

  2. A Robust and Resilient Network Design Paradigm for Region-Based Faults Inflicted by WMD Attack (United States)


    method which utilizes the limiting behavior of a birth and death process and a more parsimonious statistical sampling approach. In [4], we proposed an...Mazumder, A. Das, S. Gokalp, N. Kim, A. Sen, H. Davulcu, Spatio-Temporal Signal Recovery from Political Tweets in Indonesia , International

  3. Reducing losses inflicted by insect pests on cashew, using weaver ants as a biological control agent

    DEFF Research Database (Denmark)

    Anato, Florence; Wargui, Rosine; Sinzogan, Antonio


    BACKGROUND: Cashew (Anacardium occidentale Linnaeus) is the largest agricultural export product in Benin. However, yields and quality are lost due to inefficient pest control. Weaver ants (Oecophylla spp.) may control pests in this crop as they eat and deter pests. In Benin, cashew pest damages, ...

  4. Effects of weaver ants on fruitfly and disease-inflicted postharves ...

    African Journals Online (AJOL)

    Data were subjected to analysis of variance using GenStat Statistical Programme 12th Edition and treatment means separation was conducted based on LSD test at P ≤ 5 %. Results indicated that the incidence of fruit fly infection in orange fruits significantly (P < 0.05) decreased from 0.8 to 0.4 % as weaver ant population ...

  5. Interviewing insights regarding the fatalities inflicted by the 2011 Great East Japan Earthquake

    Directory of Open Access Journals (Sweden)

    M. Ando


    Full Text Available One hundred fifty survivors of the 11 March 2011 Great East Japan Earthquake (Tohoku-oki earthquake (Mw = 9.0 were interviewed to study the causes of deaths from the associated tsunami in coastal areas of Tohoku. The first official tsunami warning underestimated the height of the tsunami and 40% of the interviewees did not obtain this warning due to immediate blackouts and a lack of communication after the earthquake. Many chose to remain in dangerous locations based on the underestimated warning and their experiences with previous smaller tsunamis and/or due to misunderstanding the mitigating effects of nearby breakwaters in blocking incoming tsunamis. Some delayed their evacuation to perform family safety checks, and in many situations, the people affected misunderstood the risks involved in tsunamis. In this area, three large tsunamis have struck in the 115 yr preceding the 2011 tsunami. These tsunamis remained in the collective memory of communities, and numerous measures against future tsunami damage, such as breakwaters and tsunami evacuation drills, had been implemented. Despite these preparedness efforts, approximately 18 500 deaths and cases of missing persons occurred. The death rate with the age of 65 and above was particularly high, four times higher than that with other age groups. These interviews indicate that deaths resulted from a variety of reasons, but if residents had taken immediate action after the major ground motion stopped, most residents might have been saved. Education about the science behind earthquakes and tsunamis could help save more lives in the future.

  6. Self-Inflicted Wounds: Russia’s Failed Chechen and North Caucasus Policy (United States)


    Olympics in Sochi , which is a city in the Krasnodar Territory of Russia.26 Sochi is a resort area on the Black Sea coast, which nestles against the North...2014 Winter Olympics in the Black Sea city of Sochi , near the North Caucasus.244 The International Olympic Committee though, has stated they have no...the territories proximity to the planned 2014 Olympic Games in Sochi .317 The games will be located less than 200 miles from Stavropol and easily

  7. Violent Dynamics: Exploring Responsibility-Attribution for Harms Inflicted During Spontaneous Group Violence

    Directory of Open Access Journals (Sweden)

    Antje du Bois Pedain


    Full Text Available Violent encounters between groups of individuals often leave one or more of the participants dead, and it may be clear from the evidence that the physical cause of death was set by the single, deliberate act of one of the participants only. When this happens, the question arises whether, and how, responsibility for the fatal act and/or for its consequences can be attributed to other participants in the punch-up. Criminal law has long sought – and found – ways of holding others apart from the direct agent responsible for the harms caused in such encounters, although the legal constructions used differ between legal systems and often change significantly over time even within the same jurisdiction. This paper investigates the appropriateness of different criminal-law responses to these cases from two directions: first, by exploring the possible doctrinal grounds within the criminal law for attributing responsibility for the fatal act/outcome to all participants; and then by investigating the extent to which these responsibility-ascriptions are supported or challenged by insights from psychological studies of group action. Los encuentros violentos entre grupos de individuos a menudo acaban con la muerte de uno o más de los participantes, y las pruebas pueden demostrar que la causa física de la muerte fue el acto único deliberado de uno solo de los participantes. Cuando esto ocurre, se plantea la pregunta de si se puede atribuir a otros participantes en la pelea la responsabilidad por el acto fatal y/o sus consecuencias, y cómo hacerlo. Durante mucho tiempo, el derecho penal ha buscado, y encontrado, formas de retener a otros participantes, además del responsable directo de los daños causados, aunque las construcciones legales utilizadas difieren entre sistemas jurídicos y a menudo cambian significativamente a lo largo del tiempo, incluso dentro de la misma jurisdicción. Este artículo investiga la conveniencia de diferentes respuestas del derecho penal a estos casos, desde dos enfoques: primero, explorando los posibles fundamentos doctrinales dentro del derecho penal para atribuir la responsabilidad del acto / resultado fatal a todos los participantes; y a continuación, investigando hasta qué punto los estudios psicológicos sobre acciones grupales confirman o rechazan esta imputación de responsabilidad. DOWNLOAD THIS PAPER FROM SSRN:

  8. From an inflicted dependency to a positive co-operation in the domain of energy

    Energy Technology Data Exchange (ETDEWEB)

    Host, Jean-Paul; Darras, Marc [Gaz de France (France)


    The 20th World Energy Congress entitled, ''Energy Future in an Interdependent World'', is aimed at highlighting the main challenges and opportunities that the energy industry should face to contribute to sustainable development across the world. For we are very much in the face of a challenge: with the demand for energy likely to increase, the energy industry will have to get by with limited resources: as concerns energy, the gradual rarefaction of fossil fuels resources, combined with the lack of any convincing substitution options in the medium term; as concerns natural resources, or more accurately, the harm that the natural environment can bear sustainably; and as concerns capital, insofar as the huge investments needed in the field of energy will be competing with other types of investments that may appear more profitable or safer. Given this situation, two types of political and economic response can be envisioned. The first is to simply let the market run its course and relations between States play out as they normally would. This would, admittedly, make it possible to solve some of the issues raised but no one can guarantee that this will not heighten political tension and lead to dangerous dawdling with regard to the climate issue. Another option is to mobilise the international community so that the interdependency leads to some sort of positive cooperation. This would require that, building on the reflections carried out virtually everywhere, international consensus would emerge and make it possible to create and champion a shared vision, leading to the institution of an enabling environment for action for states and operators altogether. Above and beyond the trade relationship that binds the latter, they have an important part to play insofar as they can significantly contribute to sustainable development across the world through the investments they make abroad and the results of their 'research' when shared through technology transfers. In a second part, this document endeavours in each of the aforementioned fields, to describe Gaz de France contributions and to highlight the developments in the legal and contractual framework, which we see as likely to cut down the barriers encountered by a company as it takes action.

  9. Secondary skull fractures in head wounds inflicted by captive bolt guns: autopsy findings and experimental simulation. (United States)

    Perdekamp, Markus Grosse; Kneubuehl, Beat P; Ishikawa, Takaki; Nadjem, Hadi; Kromeier, Jan; Pollak, Stefan; Thierauf, Annette


    Apart from one article published by Rabl and Sigrist in 1992 (Rechtsmedizin 2:156-158), there are no further reports on secondary skull fractures in shots from captive bolt guns. Up to now, the pertinent literature places particular emphasis on the absence of indirect lesions away from the impact point, when dealing with the wounding capacity of slaughterer's guns. The recent observation of two suicidal head injuries accompanied by skull fractures far away from the bolt's path gave occasion to experimental studies using simulants (glycerin soap, balls from gelatin) and skull–brain models. As far as ballistic soap was concerned, the dimensions of the bolt's channel were assessed by multi-slice computed tomography before cutting the blocks open. The test shots to gelatin balls and to skull-brain models were documented by means of a high-speed motion camera. As expected, the typical temporary cavity effect of bullets fired from conventional guns could not be observed when captive bolt stunners were discharged. Nevertheless, the visualized transfer of kinetic energy justifies the assumption that the secondary fractures seen in thin parts of the skull were caused by a hydraulic burst effect.

  10. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)


    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective system to evaluate and optimize therapeutics. ► Show that doxycycline and dexamethasone reduce NM-caused ocular injuries ► Demonstrate that silibinin effectively reverses NM-caused ocular injury endpoints ► Suggest optimization of identified agents against ocular injuries by vesicants.

  11. Management of unusual case of self-inflicted penetrating craniocerebral injury by a nail

    Directory of Open Access Journals (Sweden)

    Kishore Kamal


    Full Text Available During war, sharp high-speed missiles have been driven inside the brain; however, in civilian practice it is rare to see such episodes. An approximately 10-cm long nail was driven inside the brain in an attempt to commit suicide by a schizophrenic patient. The case is being reported for its rarity in civilian practice and as a case of clinical interest. After investigating the patient by plain X-rays and a CT scan, he was operated by a neurosurgical team and the nail was successfully removed. In post-operative phase, patient was given medical and psychiatric care along with psychological counseling. The patient made good uneventful recovery in the post-operative phase.

  12. Automation inflicted differences on operator performance in nuclear power plant control rooms

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jonas; Osvalder, A.L. [Chalmers Univ. of Technology, Dept. of Product and Producton Development (Sweden)


    Today it is possible to automate almost any function in a human-machine system. Therefore it is important to find a balance between automation level and the prerequisites for the operator to maintain safe operation. Different human factors evaluation methods can be used to find differences between automatic and manual operations that have an effect on operator performance; e.g. Predictive Human Error Analysis (PHEA), NASA Task Load Index (NASA-TLX), Halden Questionnaire, and Human Error Assessment and Reduction Technique (HEART). Results from an empirical study concerning automation levels, made at Ringhals power plant, showed that factors as time pressure and criticality of the work situation influenced the operator's performance and mental workload more than differences in level of automation. The results indicate that the operator's attention strategies differ between the manual and automatic sequences. Independently of level of automation, it is essential that the operator retains control and situational understanding. When performing a manual task, the operator is 'closer' to the process and in control with sufficient situational understanding. When the level of automation increases, the demands on information presentation increase to ensure safe plant operation. The need for control can be met by introducing 'control gates' where the operator has to accept that the automatic procedures are continuing as expected. Situational understanding can be established by clear information about process status and by continuous feedback. A conclusion of the study was that a collaborative control room environment is important. Rather than allocating functions to either the operator or the system, a complementary strategy should be used. Key parameters to consider when planning the work in the control room are time constraints and task criticality and how they affect the performance of the joint cognitive system.However, the examined working situations were too different with respect to levels of automation and therefore it is not possible yet to propose general automation level guidelines. Further studies are still needed. (au)

  13. Adolescent injury and death: the plagues of accident, self-infliction and violence. (United States)

    Kelton, G M; Shank, J C


    Motor vehicle-related accidents and firearm-related violence are the first and second leading causes of adolescent morbidity and mortality. Fortunately, considerable progress has been made in reducing motor vehicle-related injuries and death through state-level legislation designed to decrease alcohol use and increase seat belt use. Homicide and suicide, however, are increasing dramatically among teenagers. Family violence and the epidemic of gang activity also contribute significantly to both; violence portrayed on television, in movies, and in adolescent music also has become a more significant part of teen life. Family physicians are encouraged to implement preventive strategies for combating the problems of injury and violence in their offices, their communities, and on the broader states of medical education and public policy.

  14. An unusual case of multiple self-inflicted punctures to the precordium

    LENUS (Irish Health Repository)

    Borhan, F


    Sewing needles, albeit a rare case of penetrating cardiac injury, are potentially life-threatening. We report a case of successful intra-cardiac needle removal from a 32 year old who inserted multiple needles into the chest and abdomen.

  15. A Self-Inflicted Wound: The U.S. in Lebanon 1982-1984 (United States)


    Barlett , however, found less than half that number, most of whom had not been in uniform in years. The Barlett report predicted a completely rebuilt...destroyed 15 months earlier. 2. Brian Michael Jenkins, The Lessons of Beirut: Testimony Before the Lona Commission, Santa Monica , Rand Corporation

  16. Inflicted T12 fracture-dislocation: CT/MRI correlation and mechanistic implications

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Brandon [Brigham and Women' s Hospital, Section of Neuroradiology, Department of Radiology, Boston, MA (United States); Silvera, Michelle [Children' s Hospital Boston, Division of Neuroradiology, Department of Radiology, Boston, MA (United States); Newton, Alice [Children' s Hospital Boston, Division of General Pediatrics, Boston, MA (United States); Kleinman, Paul K. [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)


    We describe the CT and MRI findings of a thoracolumbar neurocentral synchondrosis fracture-dislocation in an abused infant. The morphologic features of this classically described fracture, and the associated cervical and sacral spine injuries displayed on cross-sectional imaging, provide compelling evidence for a mechanism of massive hyperflexion and axial spinal loading. (orig.)

  17. The frequency and effect of shark-inflicted bite injuries to the reef ...

    African Journals Online (AJOL)

    Shark bite injuries on reef manta rays Manta alfredi off the coast of Inhambane, Mozambique, were examined over a three-year period (2003–2006). The frequency and seasonality of attacks, the rate of wound healing, and the possible identities of attackers were explored. This study presents the first examination of bite ...

  18. [Study of generational risk in deafness inflicted couples using deafness gene microarray technique]. (United States)

    Wang, Ping; Zhao, Jia; Yu, Shu-yuan; Jin, Peng; Zhu, Wei; DU, Bo


    To explored the significance of screening the gene mutations of deafness related in deaf-mute (deaf & dumb) family using DNA microarray. Total of 52 couples of deaf-mute were recruited from Changchun deaf-mute community. With an average age of (58.3 ± 6.7) years old (x(-) ± s). Blood samples were obtained with informed consent. Their genomic DNA was extracted from peripheral blood and PCR was performed. Nine of hot spot mutations in four most common deafness pathologic gene were examined with the DNA microarray, including GJB2, GJB3, PDS and mtDNA 12S rRNA genes. At the same time, the results were verified with the traditional methods of sequencing. Fifty of normal people served as a control group. All patients were diagnosed non-syndromic sensorineural hearing loss by subjective pure tone audiometry. Thirty-two of 104 cases appeared GJB2 gene mutation (30.7%), the mutation sites included 35delG, 176del16, 235delC and 299delAT. Eighteen of 32 cases of GJB2 mutations were 235delC (59.1%). Seven of 104 cases appeared SLC26A4 gene IVS7-2 A > G mutation. Questionnaire survey and gene diagnosis revealed that four of 52 families have deaf offspring (7.6%). When a couple carries the same gene mutation, the risk of their children deafness was 100%. The results were confirmed with the traditional methods of sequencing. There is a high risk of deafness if a deaf-mute family is planning to have a new baby. It is very important and helpful to avoid deaf newborns again in deaf-mute family by DNA microarray.

  19. Linguistic Factors Associated with Self-Inflicted Injury in Borderline Personality Disorder (United States)

    Birdwell, Benjamin Park


    The present study builds on previous research, which demonstrated higher levels of depressive and interpersonal conflict language in first-person narrative accounts of nonsuicidal self-injury (NSSI) and suicide attempt (SA) in borderline personality disorder. The present study was designed to examine the semantic similarity of time-sequences…

  20. Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Bryan Leaw


    Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

  1. Propionyl-IIGL tetrapeptide antagonizes beta-amyloid excitotoxicity in rat nucleus basalis

    NARCIS (Netherlands)

    Harkany, T.; Abraham, I.; Laskay, G.; Timmerman, W.; Jost, K.; Zarandi, M.; Penke, B; Nyakas, Csaba; Luiten, P.G.M.


    A putative tetrapeptide beta-amyloid (A beta) antagonist (propionyl-Ile-Ile-Gly-Leu [Pr-IIGL]) based on the [31-34] sequence of A beta was previously shown to rescue astrocytes from A beta-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in

  2. Spinal Cord Transcriptomic and Metabolomic Analysis after Excitotoxic Injection Injury Model of Syringomyelia. (United States)

    Mohrman, Ashley E; Farrag, Mahmoud; Huang, He; Ossowski, Stephan; Haft, Stephanie; Shriver, Leah P; Leipzig, Nic D


    Syringomyelia is a condition of the spinal cord in which a syrinx, or fluid-filled cavity, forms from trauma, malformation, or general disorder. Previous work has shown that in noncanalicular syringomyelia irregular flow and pressure conditions enhance the volumetric growth of syrinxes. A better understanding of the underlying molecular pathways associated with syrinx formation will unveil targets for treatments and possibly prevention of syringomyelia in the future. In this study, we performed an established surgical induction of a syrinx using quisqualic acid and kaolin injections in rats to characterize the injury at the molecular level by RNA sequencing and metabolomics techniques at three and six weeks post-injury. Syrinxes averaging nearly 10 mm in length formed in the rats' spinal cords; however, smaller syrinxes were also detected in saline injected surgical shams, complicating interpretation of results. Our current results indicate a robust immune response coupled with overall decreases in neuronal signal transmission of syrinx containing animals compared with controls. Although transcriptional changes indicated gliosis and loss of neurons, no neuropathic pain was detected by von Frey allodynia testing. Unique transporters were revealed to be highly dysregulated, including significant increases in betaine/glycine transporter (BGT-1), K+/Cl- co-transporter (KCC4), and aquaporin 1 (AQP1), along with the upregulation of small molecule osmolytes taurine and betaine. The identified metabolites are of particular interest because of their involvement in osmotic homeostasis and need to be investigated further for their specific involvement in trauma-induced syrinxes.

  3. A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity

    DEFF Research Database (Denmark)

    Verma, Pushpa; Augustine, George J; Ammar, Mohamed-Raafet


    Evidence has begun to emerge for microRNAs as regulators of synaptic signaling, specifically acting to control postsynaptic responsiveness during synaptic transmission. In this report, we provide evidence that Drosophila melanogaster miR-1000 acts presynaptically to regulate glutamate release at ...

  4. Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington’s Disease (United States)


    neurotransmission in GPe and GPi. It is still premature to speculate about a particular treatment strategy at this point without knowing the exact role...Disease. J. Neuropathol. Exp. Neurol. 57: 369-384. Page: 10 APPENDIX 1 Journal of CHEMICAL NEUROANATOMY ELSEVIER Journal of Chemical Neuroanatomy 22...inputs from any functional regions of GPi, Y. Smith et al. /Journal of Chemical Neuroanatomy 22 (2001) 13-42 17 but receive substantial innervation

  5. Spatial discrimination deficits by excitotoxic lesions in the MORRIS WATER ESCAPE TASK

    NARCIS (Netherlands)

    Spowart-Manning, L.; Staay, van der F.J.


    The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil were assessed on spatial performance of rats with bilateral lesions of the entorhinal cortex (EC), which is thought to model early changes in the brains of patients suffering from Alzheimer's disease. In the present study,

  6. Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

    Directory of Open Access Journals (Sweden)

    An Y


    Full Text Available Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS-(tetrazole-5yl glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox. In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2 in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI2

  7. Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

    Directory of Open Access Journals (Sweden)

    Cavalcante-Lima H.R.


    Full Text Available We determined if the dorsal raphe nucleus (DRN exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11 or 1 µg/0.2 µl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10 through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment and a low dose of dietary captopril (1 mg/g chow. From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake whereas PB-DRN did not exceed 2 ml (P < 0.001. Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001. Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001. These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

  8. Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to the rat medial septum

    NARCIS (Netherlands)

    Mulder, J.; Harkany, T.; Czollner, K.; Cremers, T.I.F.H.; Keijser, J.; Nyakas, C.; Luiten, P.G.M.


    Clinical trials show beneficial effects of acetylcholinesterase (AChE) inhibitors, including galantamine, on cognitive functions in patients with mild to moderate Alzheimer's disease. Galantamine shows a dual action profile by also acting as an allosteric modulator of nicotinic acetylcholine

  9. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R


    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy fib...

  10. Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesis

    DEFF Research Database (Denmark)

    Baskys, Andrius; Bayazitov, Ildar; Fang, Liwei


    neuroprotective activation of group I metabotropic glutamate receptors. Brain Research, Molecular Brain Research 117, 196-205.]. In the present study, we used organotypic hippocampal culture preparation to examine specific phospholipase C (PLC) inhibitor U73122 effects on DHPG-induced neuroprotection, changes......-CA1 pathway. The fEPSP depression was not affected by the PLC inhibitor U73122. In contrast, prolonged (2-h) treatment of cultures with DHPG induced a significant protective effect that was blocked by a PLC inhibitor U73122 but not by its inactive analog U73343. Voltage-clamp measurements...... a PLC involvement. Since activation of PLC is thought to be associated with cell proliferation, we investigated whether group I mGluR agonist DHPG or subtype antagonists LY367385 and MPEP have an effect on dentate granule cells expressing immature neuronal marker TOAD-64. DHPG (100 microM, 72 h...

  11. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Haruki Odaka

    Full Text Available Several lines of evidence demonstrate that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent antioxidants may therefore be effective in the treatment of such diseases. Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been studied using several cell types including mesencephalic neurons, and is recognized as a potent radical scavenger. Here, we examined whether cabergoline exerts neuroprotective effects against oxidative stress through a receptor-mediated mechanism in cultured cortical neurons. We found that neuronal death induced by H₂O₂ exposure was inhibited by pretreatment with cabergoline, while this protective effect was eliminated in the presence of a dopamine D2 receptor inhibitor, spiperone. Activation of ERK1/2 by H₂O₂ was suppressed by cabergoline, and an ERK signaling pathway inhibitor, U0126, similarly protected cortical neurons from cell death. This suggested the ERK signaling pathway has a critical role in cabergoline-mediated neuroprotection. Furthermore, increased extracellular levels of glutamate induced by H₂O₂, which might contribute to ERK activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L-type Ca²⁺ channel demonstrated a survival effect against H₂O₂. Interestingly, we found that cabergoline increased expression levels of glutamate transporters such as EAAC1. Taken together, these results suggest that cabergoline has a protective effect on cortical neurons via a receptor-mediated mechanism including repression of ERK1/2 activation and extracellular glutamate accumulation induced by H₂O₂.

  12. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. (United States)

    Odaka, Haruki; Numakawa, Tadahiro; Adachi, Naoki; Ooshima, Yoshiko; Nakajima, Shingo; Katanuma, Yusuke; Inoue, Takafumi; Kunugi, Hiroshi


    Several lines of evidence demonstrate that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent antioxidants may therefore be effective in the treatment of such diseases. Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been studied using several cell types including mesencephalic neurons, and is recognized as a potent radical scavenger. Here, we examined whether cabergoline exerts neuroprotective effects against oxidative stress through a receptor-mediated mechanism in cultured cortical neurons. We found that neuronal death induced by H₂O₂ exposure was inhibited by pretreatment with cabergoline, while this protective effect was eliminated in the presence of a dopamine D2 receptor inhibitor, spiperone. Activation of ERK1/2 by H₂O₂ was suppressed by cabergoline, and an ERK signaling pathway inhibitor, U0126, similarly protected cortical neurons from cell death. This suggested the ERK signaling pathway has a critical role in cabergoline-mediated neuroprotection. Furthermore, increased extracellular levels of glutamate induced by H₂O₂, which might contribute to ERK activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L-type Ca²⁺ channel demonstrated a survival effect against H₂O₂. Interestingly, we found that cabergoline increased expression levels of glutamate transporters such as EAAC1. Taken together, these results suggest that cabergoline has a protective effect on cortical neurons via a receptor-mediated mechanism including repression of ERK1/2 activation and extracellular glutamate accumulation induced by H₂O₂.

  13. AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated and dependent upon receptor desensitization

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S


    was blocked was seen as early as 5 DIV since 10 microM MK-801 did not completely block the response whereas 10 microM NBQX did. The 2,3-benzodiazepine GYKI compounds, which have been reported to be selective non-competitive AMPA receptor antagonists, were here observed to block the AMPA toxicity...

  14. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress (United States)


    amino- Department of Psychiatry, propane (DOI), altered temperature regulation, wet dog Case Western Reserve University, shakes and head shakes in rats or... hypersensitive site. JNeurosci 8, 2640-2651. Hernandez L. F., Segovia G., and Mora F. (2003) Effects of activation of NMDA and AMPA glutamate... hypersensitive D2 autoreceptors in the not only is there a preexistent differential effect on extra- VTA, which on activation would rapidly decrease

  15. The Fire Challenge: A Case Report and Analysis of Self-Inflicted Flame Injury Posted on Social Media. (United States)

    Avery, Andrew H; Rae, Lisa; Summitt, J Blair; Kahn, Steven Alexander


    With the advent of social media platforms such as Facebook and YouTube, online dissemination of exhibitionist videos has gained popularity. One recent disturbing trend is the "fire challenge" wherein a participant douses his or herself in a household accelerant such as isopropyl alcohol or acetone, sets him or herself ablaze, and attempts to extinguish the flames before serious burns are incurred. As expected, participants in the "fire challenge" often accidentally suffer serious burns. A 17-year-old white male was recently treated at our burn center after participating in the "fire challenge." He suffered 15% TBSA full and partial thickness burns requiring split thickness skin grafting to his abdomen. He reported lighting himself on fire because he had seen this stunt performed on the internet. A search for "fire challenge" and similar terms was conducted on YouTube ( Gender and ethnicity of each participant were documented. Burn size, burn depth, and age of video participant were estimated by two attending burn surgeons evaluating YouTube videos. Results were reported with descriptive statistics. The search yielded thousands of hits, mostly home videos, compilations of stunts, and commentaries. After omitting duplicate and irrelevant videos, 50 videos were selected for the study. Of these, 13 videos included postburn footage demonstrating burn wounds of various location, size, and severity. Of these burns, the median TBSA burned was 4 ± 2.7% with a maximum size of 10%. Superficial and partial thickness burns were sustained on the torso (10/13, 77%), face (4/13, 31%), and extremities (2/13, 15%). Full thickness burns were seen in 2/13 videos. Some burn wounds were obscured by dressings. Of the 50 videos reviewed, 45/50 participants (90%) were male and 32/50 (64%) were African American with 29/50 participants (58%) estimated to be under age 20. The "fire challenge" is a popular social media phenomenon, but it can result in severe injury as seen with the patient at our institution. The lure of a challenge and potential for a shocking video to "go viral" might entice people to mimic this risky behavior. This study shows a disturbing trend, but undoubtedly only reflects a small portion of actual participants. A disproportionate number of videos featured young African American males, making this a target population for education and prevention efforts. Our patient's TBSA exceeded the maximum found on YouTube, suggesting that less severe burns may be posted online while larger burns are not, diminishing perceived risk and encouraging this behavior.

  16. Periocular and anterior orbital necrosis after upper eyelid gold weight loading: operation-related or self-inflicted?

    Directory of Open Access Journals (Sweden)

    Schwartz R


    Full Text Available Roy Schwartz,1 Ran Ben Cnaan,1 Ophir Schein,2 Michael Giladi,3 Michal Raz,4 Igal Leibovitch11Oculoplastic and Orbital Institute, Department of Ophthalmology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Department of Plastic Surgery, Assaf Harofeh Medical Center, Tzrifin, Israel; 3Infectious Disease Unit, 4Pathology Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: A 44-year-old woman, who had undergone gold-weight implantation due to facial palsy and lagophthalmos, arrived at the ophthalmology ward with eyelid swelling and erythema, which rapidly deteriorated under intravenous antibiotics to a necrotic process involving the periocular tissues, the eye, and the anterior orbit. Despite prompt removal of the gold weight, the patient's ocular and systemic condition continued to deteriorate, necessitating evisceration and debridement of necrotic tissue. Cultures showed growth of Staphylococcus epidermidis, Staphylococcus capitis, Candida glabrata, and Candida albicans, and histopathology demonstrated an acute nonspecific necrotizing panophthalmitis. Later on, the patient was admitted to a plastic surgery ward with recurrent severe burns of her thigh, which were highly suggestive of being self-induced, raising the possibility of self-induced damage.Keywords: evisceration, factitious disorder, lagophthalmos

  17. Self-inflicted foreign bodies in lower genitourinary tract in males: Our experience and review of literature

    Directory of Open Access Journals (Sweden)

    Nagabhushana Mahadevappa


    Conclusions: Foreign body insertion to lower urinary tract was rare. A main cause for insertion of foreign bodies was autoerotism, misconceptions regarding masturbation, and underlying psychiatric illness. In addition to suitable method of surgical removal, counseling and psychiatric evaluation are necessary to prevent recurrences or for early detection of psychiatric problems.

  18. Autopsy audit of intentional burns inflicted by self or by others in north India-5 year snapshot. (United States)

    Kumar, Sachil; Verma, Anoop K; Singh, Uma Shankar; Singh, Raghvendra


    The incidence of suicide and homicide is on the increase worldwide, including India. One million people die annually due to suicides and homicides alone. Thus this study had been undertaken to find out the material and social causes of burn and to assess the socio-demographic characteristics between suicide and homicide. This retrospective study was carried out on 1393 fatal burn cases (2008-2012) who were autopsied at the mortuary of King George's Medical University, Lucknow, India. Data retrieved include: age, sex, type of family, marital status, place of incidence, psychological status and burn size (TBSA). The results were presented in Mean ± SD and percentages and analyzed with SPSS 16.0. Out of the total 1369 cases of burns, 536 cases (38.5%) were homicidal deaths in comparison to 857 cases (61.5%) of suicidal deaths. Female predominance was seen in both suicidal and homicidal deaths with peak age 30-39 years in suicides in contrast to 40-49 years in homicides. At younger age ≤19 years, the victims of suicide is almost similar to the victims of homicide; but at extremes of ages below 10 years and above 60 years, homicides were relatively more common than suicides. Married victims were predominant in the homicidal group (66.6%). There is no quite difference at the place where burn occurs. Depression and anxiety disorders were the most frequent psychiatric co-morbidities associated with suicidal behaviours. Patients from suicidal group suffered significantly larger burns than from homicidal group. Hence, this study was planned with a purpose to know the magnitude and the socio-cultural factors of the problem of burns to more clearly understand the dynamics surrounding these deaths, so that a sound prevention programme could be suggested, planned and implemented for reducing the incidence of fatal burns. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  19. Violence-related behaviors and self-inflicted injuries among 15-18 year old Iranian adolescents. (United States)

    Baheiraei, Azam; Hamzehgardeshi, Zeinab; Mohammadi, Mohammad Reza; Nedjat, Saharnaz


    In this population-based cross-sectional study, we determined the prevalence of intentional injuries and associated factors among 1201 adolescents in Tehran, Iran. Overall, 63.9% of adolescents had at least one intentional injury behavior which was significantly higher in males. Gender preference for males by parents, very high or very low supervision, waterpipe smoking, and alcohol consumption were significantly associated with injuries in females. In addition, poor wealth index, parental punishment and smoking were incriminating factors in males.

  20. Reaching for the bottle of pesticide--a cry for help. Self-inflicted poisonings in Sri Lanka

    DEFF Research Database (Denmark)

    Konradsen, Flemming; Hoek, Wim van der; Peiris, Pushpalatha


    in general, conveying misgiving, anger, sadness, hopelessness, frustration, or simply a way to manipulate a situation to one's own advantage. The effects of alcohol misuse are especially important in understanding self-harm at the community level in terms of the impact they have on the domestic environment....... Also, issues around "love affairs," arranged marriages and domestic physical, sexual or psychological abuse in the domestic environment are referred to by many self-harmers or their relatives as a reason for ingesting poison. Clearly, easy access to lethal pesticides by impulsive individuals often...

  1. Baculovirus-challenge and poor nutrition inflict within-generation fitness costs without triggering transgenerational immune priming. (United States)

    Shikano, Ikkei; Hua, Kevin Ngoc; Cory, Jenny S


    Invertebrate hosts that survive pathogen challenge can produce offspring that are more resistant to the same pathogen via immune priming, thereby improving the fitness of their offspring in the same pathogen environment. Most evidence for immune priming comes from exposure to bacteria and there are limited data on other groups of pathogens. Poor parental nutrition has also been shown to result in the transgenerational transfer of pathogen resistance and increased immunocompetence. Here, we combine exposure to an insect DNA virus with a change in the parental diet to examine both parental costs and transgenerational immune priming. We challenged the cabbage looper, Trichoplusia ni, with a low dose of the baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and altered dietary protein to carbohydrate ratio (p:c ratio) after virus exposure. Insects fed a low protein diet had lower haemolymph protein concentrations, and exhibited costs of smaller pupae and slower development, while survivors of virus challenge developed more slowly, irrespective of p:c ratio, and those that were virus-challenged and fed on a low protein diet showed a reduction in haemocyte density. In addition, AcMNPV-challenged parents laid fewer eggs earlier in egg laying although egg size was the same as for unchallenged parents. There was no evidence for increased resistance to AcMNPV (immune priming) or changes in haemocyte number (as proxy for constitutive cellular immunity) in the offspring either as a result of parental AcMNPV-challenge or low dietary p:c ratio. Therefore, although pathogen-challenge and nutritional changes can affect host development and reproduction, this does not necessarily translate into transgenerational immune priming. Our findings contrast with an earlier study on another type of baculovirus, a granulovirus, where immune priming was suggested. This indicates that transgenerational immune priming is not universal in invertebrates and is likely to depend on the host-pathogen system, or the level of pathogen exposure and the type of dietary manipulation. Identifying whether immune priming or transgenerational effects are relevant in field populations, remains a challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Situating suicide as an anthropological problem: ethnographic approaches to understanding self-harm and self-inflicted death. (United States)

    Staples, James; Widger, Tom


    More than a century after Durkheim's sociological classic placed the subject of suicide as a concern at the heart of social science, ethnographic, cross-cultural analyses of what lie behind people's attempts to take their own lives remain few in number. But by highlighting how the ethnographic method privileges a certain view of suicidal behaviour, we can go beyond the limited sociological and psychological approaches that define the field of 'suicidology' in terms of social and psychological 'pathology' to engage with suicide from our informants' own points of view-and in so doing cast the problem in a new light and new terms. In particular, suicide can be understood as a kind of sociality, as a special kind of social relationship, through which people create meaning in their own lives. In this introductory essay we offer an overview of the papers that make up this special issue and map out the theoretical opportunities and challenges they present.

  3. Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá


    investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were...... assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects...

  4. Magnesium Sulfate Prevents Neurochemical and Long-Term Behavioral Consequences of Neonatal Excitotoxic Lesions: Comparison Between Male and Female Mice. (United States)

    Daher, Ismaël; Le Dieu-Lugon, Bérénice; Dourmap, Nathalie; Lecuyer, Matthieu; Ramet, Lauriane; Gomila, Cathy; Ausseil, Jérôme; Marret, Stéphane; Leroux, Philippe; Roy, Vincent; El Mestikawy, Salah; Daumas, Stéphanie; Gonzalez, Bruno; Leroux-Nicollet, Isabelle; Cleren, Carine


    Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  5. Identification of Bax-Interacting Proteins in Oligodendrocyte Progenitors during Glutamate Excitotoxicity and Perinatal Hypoxia–Ischemia

    Directory of Open Access Journals (Sweden)

    Sopio Simonishvili


    Full Text Available OPC (oligodendrocyte progenitor cell death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis.

  6. Minimal impairment in a rat model of duration discrimination following excitotoxic lesions of primary auditory and prefrontal cortices

    Directory of Open Access Journals (Sweden)

    Shraddha S Pai


    Full Text Available We present a behavioral paradigm for the study of duration perception in the rat, and report the result of neurotoxic lesions that have the goal of identifying sites that mediate duration perception. Using a two-alternative forced-choice paradigm, rats were either trained to discriminate durations of pure tones (range=[200,500]ms; boundary=316ms; Weber fraction after training=0.24+/-0.04, or were trained to discriminate frequencies of pure tones (range=[8,16]kHz; boundary=11.3kHz; Weber=0.16+/-0.11; the latter task is a control for non-timing-specific aspects of the former. Both groups discriminate the same class of sensory stimuli, use the same motions to indicate decisions, have identical trial structures, and are trained to psychophysical threshold; the tasks are thus matched in a number of sensorimotor and cognitive demands. We made neurotoxic lesions of candidate timing-perception areas in the cerebral cortex of both groups. Following extensive bilateral lesions of the auditory cortex, the performance of the frequency-discrimination group was significantly more impaired than that of the duration-discrimination group. We also found that extensive bilateral lesions of the medial prefrontal cortex resulted in little to no impairment of both groups. The behavioral framework presented here provides an audition-based approach to study the neural mechanisms of time estimation and memory for durations.

  7. Beta-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis.

    NARCIS (Netherlands)

    Harkany, T; Abraham, [No Value; Timmerman, W; Laskay, G; Toth, B; Sasvari, M; Konya, C; Sebens, JB; Korf, J; Nyakas, C; Zarandi, M; Soos, K; Penke, B; Luiten, PGM

    Whereas a cardinal role for beta-amyloid protein (A beta) has been postulated as a major trigger of neuronal injury in Alzheimer's disease, the pathogenic mechanism by which A beta deranges nerve cells remains largely elusive. Here we report correlative in vitro and in vivo evidence that an

  8. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity

    DEFF Research Database (Denmark)

    Xapelli, S; Bernardino, L; Ferreira, R


    The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Exposure of 2-week-old slice cultures, derived from 7-...

  9. Effects of TRH and its analogues on primary cortical neuronal cell damage induced by various excitotoxic, necrotic and apoptotic agents. (United States)

    Jantas, D; Jaworska-Feil, L; Lipkowski, A W; Lason, W


    The tripeptide thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2) has been shown to possess neuroprotective activity in in vitro and in vivo models. Since its potential utility is limited by relatively rapid metabolism, metabolically stabilized analogues have been constructed. In the present study we investigated the influence of TRH and its three stable analogues: Montirelin (MON, CG-3703), RGH-2202 (L-6-keto-piperidine-2carbonyl-l-leucyl-l-prolinamide) and Z-TRH (N-carbobenzyloxy-pGlutamyl-Histydyl-Proline) in various models of mouse cortical neuronal cell injury. Twenty four hour pre-treatment with TRH and its analogues in low micromolar concentrations attenuated the neuronal cell death evoked by excitatory amino acids (EAAs: glutamate, NMDA, kainate, quisqualate) and hydrogen peroxide. All the peptides showed neuroprotective action on staurosporine (St)-evoked apoptotic neuronal cell death, but this effect was caspase-3 independent. Interestingly, in mixed neuronal-glial cell preparations only MON decreased St- and glutamate-evoked neurotoxicity. None of the peptides inhibited the doxorubicin- and lactacystin-induced neuronal cortical cell death, agents acting via activation of death receptor (FAS) or inhibition of proteasome function, respectively. Furthermore, we found that neither inhibitors of PI3-K (wortmannin, LY 294002) nor MAPK/ERK1/2 (PD 098059, U 0126) were able to inhibit neuroprotective properties of TRH and MON in St model of apoptosis. The protection mediated by TRH and MON it that model was also not connected with influence of peptides on the pro-apoptotic GSK-3beta and JNK protein kinase expression and activity. Further studies showed that calpains, calcium-activated proteases were induced by Glu, but not by St in cortical neurons. Moreover, the Glu-evoked increase in spectrin alpha II cleavage product induced by calpains was blocked by TRH. The obtained data showed that the potency of TRH and its analogues in inhibiting EAAs- and H(2)O(2)-induced neuronal cell death from the highest to lowest activity was: MON>TRH>Z-TRH>RHG. Interestingly, all peptides were active against St-induced apoptosis, however, on concentration basis MON was far more potent than the other peptides. None of the peptides inhibited Dox- and LC-evoked apoptotic cell death. Additionally, the data exclude potential role of pro-survival (PI3-K/Akt and MAPK/ERK1/2) and pro-apoptotic (GSK-3beta and JNK) pathways in neuroprotective effects of TRH and its analogues on St-induced neuronal apoptosis. Moreover, the results point to involvement of the inhibition of calpains in the TRH neuroprotective effect in Glu model of neuronal cell death.

  10. Sex and regional differences in effects of chronic intermittent ethanol exposure on subsequent excitotoxic challenges in hippocampal slice cultures. (United States)

    Walls, Shawn A; Rosenwasser, Alan M; Devaud, Leslie L


    The organotypic hippocampal slice culture technique was used to study how the effects of repeated ethanol withdrawal might differ between males and females at the cellular level, including potential modulation of subsequent insults. A chronic intermittent ethanol (CIE) exposure paradigm was employed, with 3 days of exposure followed by 24 h withdrawal for 3 cycles. Slices were next exposed to corticosterone (CORT) or pentylenetetrazol (PTZ) for 24 h then imaged for propidium iodide (PI) signal intensities. There were sex-selective responses in the CA1 region and dentate gyrus of the hippocampal slice cultures to treatment with CIE and/or CORT or PTZ. The 50 mM CIE alone generally did not increase the PI signal, but enhanced sensitivity to the toxic effects of CORT (particularly for females) and PTZ (particularly for males). In contrast, 100 mM CIE elicited a toxic response that was greater in females than males, and was exacerbated by exposure to PTZ. These data showed that hippocampal sexual dimorphism influences sensitivity to ethanol and other toxic chemicals even in an immature state. Low-dose CIE may attenuate harm from additional challenges in a hippocampal sex- and region-selective manner. These findings add to the growing evidence of important neurobiological sex differences in responses to chronic ethanol exposure and withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata

    National Research Council Canada - National Science Library

    Hatzipetros, Theo; Raudensky, Jamie G; Soghomonian, Jean-Jacques; Yamamoto, Bryan K


    .... We report here that subchronic haloperidol administration after a high-dose regimen of METH produces a heretofore unrecognized toxicity to GABAergic cells, as reflected by GAD67 mRNA expression...

  12. A autoviolência, objeto da sociologia e problema de saúde pública: a sociological concern and a public health problem Self-inflicted violence

    Directory of Open Access Journals (Sweden)

    Maria Cecília de Souza Minayo


    Full Text Available Este artigo tem dois objetivos: o primeiro é refletir sobre o significado do suicídio enquanto questão sociológica, comentando um artigo produzido por E. D. Nunes (1998 sobre a célebre obra de Durkheim. O segundo é discutir a mesma problemática no campo da saúde pública, analisando as contribuições do pai da sociologia, as abordagens epidemiológicas e das áreas da psicologia, psiquiatria e psicanálise, ressaltando as contribuições de autores nacionais. O texto apresenta informações sobre o quadro epidemiológico brasileiro e conclui, mostrando as causas violentas, apenas do ponto de vista analítico, podem ser estudadas separadamente, necessitando sempre de uma vigilância epistemológica e epidemiologica para a construção de indicadores que possam contribuir para transformações. Sim, porque os dados de violência hoje necessitam ser vistos no quadro de crise social e de mudanças pelas quais o país está passando.This paper has two objectives. The first is to reflect on the meaning of suicide as a sociological issue, commenting on an article by E.D. Nunes (1988 on the famous work by Durkheim. The second is to discuss the same issue within the field of public health, analyzing the contributions by the father of sociology and approaches by the fields of epidemiology, psychology, psychiatry, and psychoanalysis, highlighting the work of Brazilian authors. The paper presents information on the Brazilian epidemiological context and concludes by demonstrating that only from an analytical point of view can violent causes as a whole can be studied separately. Thus, they constantly require epistemological and epidemiological surveillance to construct indicators capable of contributing to change. This is all the more true because data on current violence need to be viewed within the context of the social crisis and changes Brazil is undergoing.

  13. The loss of imprinted DNA methylation in mouse blastocysts is inflicted to a similar extent by in vitro follicle culture and ovulation induction. (United States)

    Saenz-de-Juano, M D; Billooye, K; Smitz, J; Anckaert, E


    Does in vitro follicle culture (IFC) have an effect on maintenance of imprinted DNA methylation in preimplantation mouse embryos? We report similar alterations in the methylation pattern of H19 imprinted maternally expressed transcript (H19), small nuclear ribonucleoprotein polypeptide N (Snrpn) and mesoderm specific transcript (Mest) imprinted genes in mouse blastocysts obtained after ovulation induction and IFC. Furthermore, we observed no differences in the gene expression of maternal effect proteins related with imprinting maintenance between superovulated in vivo grown or IFC oocytes. Assisted reproductive technology is associated with adverse post-natal outcomes such as increased risk of premature birth, altered birthweight, congenital anomalies and genomic imprinting syndromes in human and in animal models. Previous studies have shown that ovulation induction allowed normal imprinting establishment in mouse oocytes, but interfered with imprinting maintenance during preimplantation . Normal imprinting establishment was also observed in mouse oocytes derived from a standardized IFC from the early pre-antral follicle stage. The methylation profiles of differentially methylated regions (DMRs) of three key imprinted genes (H19, Snrpn and Mest) were compared at hatched blastocyst stage between embryos obtained from IFC or superovulated oocytes, each subjected to IVF and preimplantation in vitro culture (IVC); in non-manipulated in vivo produced late blastocyst (control) and in in vivo produced 2-cell embryos that were in vitro cultured until the hatched blastocyst stage (to assess the effect of IVC). Two different mice strains (Mus musculus C57BL/6J X CBA/Ca and Mus musculus B6 (CAST7)) were used to discriminate between maternal and paternal alleles of imprinted genes. Additionally, a limiting-dilution bisulfite-sequencing technique was carried out on individual embryos in order to avoid amplification bias. To assess whether IFC and ovulation induction differentially affect the mRNA expression of imprinting maintenance genes in the oocyte, a comparison of DNA methyltransferase 1 (Dnmt1o), methyl-CpG binding domain protein 3 (MBD3) and developmental pluripotency-associated 3 (Dppa3) was performed by qPCR between in vivo and in vitro grown oocytes at the germinal vesicle and metaphase II (MII) stage. Results showed a loss of global imprinted DNA methylation in all in vitro manipulated embryos, due to an increase in the amount of abnormal alleles (vitro maturation of oocytes (IVM) is a patient-friendly alternative to conventional ovarian stimulation in PCOS patients. IFC is an emerging technology in human oncofertility. The results of this study show for the first time that in vitro oocyte culture induces no additional epigenetic alterations compared with conventional ovulation induction, at least for imprinted genes at the hatched blastocyst stage. The mouse IFC system can be used to test the sensitivity of the oocyte during its growth and maturation to several nutritional, metabolic and hormonal conditions possibly linked to epigenetic alterations. N/A. This study received funding by Strategic Research Programs-Groeiers (OZR/2014/97), IWT/TBM/110680 and by UZ Brussel Fonds Willy Gepts (WFWG 2013). There is no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:

  14. [Violence in families and its prevention. Also a plea for abolishing the parental right to inflict physical punishment. A report of the "Violence Commission" of the federal government]. (United States)

    Remschmidt, H; Schmidt, M H; Strunk, P


    Violence in families is rather frequent. Different forms of violent acts can be distinguished: violence between partners, violence between parents and children, violence among siblings, and violence against elder family members. This report gives an overview--with the emphasis on violence in families--of the work of the "Violence Commission" of the Federal Government. This commission worked out proposals for intervention in the case of intrafamiliar violence as well as for prevention. Two proposals of the commission are explained in detail: (1) Rejection of violence and prohibition of corporal punishment in education and (2) punishability of conjugal violation.

  15. Neuroprotective Efficacy of Mitochondrial Antioxidant MitoQ in Suppressing Peroxynitrite-Mediated Mitochondrial Dysfunction Inflicted by Lead Toxicity in the Rat Brain. (United States)

    Maiti, Arpan Kumar; Saha, Nimai Chandra; More, Sunil S; Panigrahi, Ashish Kumar; Paul, Goutam


    Lead (Pb) is one of the most pollutant metals that accumulate in the brain mitochondria disrupting mitochondrial structure and function. Though oxidative stress mediated by reactive oxygen species remains the most accepted mechanism of Pb neurotoxicity, some reports suggest the involvement of nitric oxide (•NO) and reactive nitrogen species in Pb-induced neurotoxicity. But the impact of Pb neurotoxicity on mitochondrial respiratory enzyme complexes remains unknown with no relevant report highlighting the involvement of peroxynitrite (ONOO-) in it. Herein, we investigated these effects in in vivo rat model by oral application of MitoQ, a known mitochondria-specific antioxidant with ONOO- scavenging activity. Interestingly, MitoQ efficiently alleviated ONOO--mediated mitochondrial complexes II, III and IV inhibition, increased mitochondrial ATP production and restored mitochondrial membrane potential. MitoQ lowered enhanced caspases 3 and 9 activities upon Pb exposure and also suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein-bound 3-nitrotyrosine. To ascertain our in vivo findings on mitochondrial dysfunction, we carried out similar experiments in the presence of different antioxidants and free radical scavengers in the in vitro SHSY5Y cell line model. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase suggesting the predominant involvement of ONOO- compared to •NO and O2•-. However, dimethylsulphoxide and catalase failed to provide protection signifying the noninvolvement of •OH and H2O2 in the process. The better protection provided by MitoQ in SHSY5Y cells can be attributed to the fact that MitoQ targets mitochondria whereas mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase are known to target mainly cytoplasm and not mitochondria. Taken together the results from the present study clearly brings out the potential of MitoQ against ONOO--induced toxicity upon Pb exposure indicating its therapeutic potential in metal toxicity.

  16. Terror-inflicted thermal injury: A retrospective analysis of burns in the Israeli-Palestinian conflict between the years 1997 and 2003. (United States)

    Haik, Josef; Tessone, Ariel; Givon, Adi; Liran, Alon; Winkler, Eyal; Mendes, David; Goldan, Oren; Bar-Meir, Eran; Regev, Eli; Orenstein, Arie; Peleg, Kobi


    Terror attacks have changed in the past decade, with a growing tendency toward explosives and suicide bombings, which led to a rise in the incidence of thermal injuries among victims. The Israeli-Palestinian conflict of October 2000 marked a turning point when an organized terror campaign commenced. This article presents data of terror-associated burns from the Israeli National Trauma Registry (ITR) during the years 1997 to September 2000 and October 2000 to 2003. We analyzed demographic and clinical characteristics of 219 terror-related burn patients and 6,546 other burn patients admitted to hospitals in Israel between 1997 and 2003. Data were obtained from the ITR. Burns contributed about 9% of all terror related trauma and about 5% of all other trauma (p Terror-related burns afflict Jewish males more than predicted by their percentage in the population, whereas other burns afflict non-Jewish males more than predicted. Adults and young adults (15-59 years) are the predominant group in terror-related burns (80%), whereas children younger than 15 years are the predominant group in other burns (50%). Large burns (20% to 89% total body surface area) are more common in terror casualties, with greater mortality (6.4% in terror-related versus 3.4% in others; p = 0.0258). Although the incidence of burns has risen because of an organized campaign, this change was noticeable in other trauma forms as well in similar proportions. Terror-related burns afflict a targeted population, and generally take on a more severe course with greater mortality rates, thus requiring appropriate medical treatment.

  17. Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant

    DEFF Research Database (Denmark)

    Petersen, Jens E V; Bouwens, Eveline A M; Tamayo, Ibai


    malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRα1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR...... functions. CIDRα1.1 severely impaired endothelial PC activation and effectively blocked APC-mediated activation of protease-activated receptor-1 (PAR1) and associated barrier protective effects of APC on endothelial cells. A soluble EPCR variant (E86A-sEPCR) bound CIDRα1.1 with high affinity and did...... contributions of PfEMP1-induced protein C pathway defects in the pathogenesis of severe malaria. Furthermore, the E86A-sEPCR decoy provides a proof-of-principle strategy for the development of novel adjunct therapies for severe malaria....

  18. Insect sting-inflicted systemic reactions: attitudes of patients with insect venom allergy regarding after-sting behavior and proper administration of epinephrine. (United States)

    Goldberg, A; Confino-Cohen, R


    Patients with insect venom allergy are at higher risk for development of a recurrent systemic reaction after re-sting. This risk significantly decreases with venom immunotherapy. Patients with insect venom allergy should be able to distinguish a life-threatening systemic reaction from all other various reactions after an insect sting. Accidental epinephrine injection by EpiPen has been reported in the past. Therefore patients with venom allergy should also be well trained in self-administration of their epinephrine when needed. Our objective was to assess patients' attitudes regarding after-sting behavior and their capability to correctly self-administer the epinephrine autoinjector. All patients with venom allergy attending our allergy unit either before commencement of or during venom immunotherapy answered a questionnaire addressing various aspects of their intended after-sting behavior. Using an EpiPen trainer device, patients' performance of EpiPen self-administration was evaluated. Ninety-six patients participated in the study. Seventy-six of them were equipped with an EpiPen device. Less than 30% of these patients carried it at all times. After re-sting, 50 (54%) patients planned to wait for the development of other symptoms before taking any further action. Twenty-two percent of the patients said that after re-sting they would immediately administer their EpiPen. Proper EpiPen administration technique was demonstrated by 44% of the patients. Having not reached the maintenance dose correlated with a better compliance with carrying of the EpiPen. EpiPen instruction provided by an allergist correlated with a better EpiPen administration technique by the patients. Many patients with venom allergy hold wrong ideas about after-sting behavior. Compliance with carrying EpiPen at all times and the ability to correctly administer it are both poor in most patients. Thorough and probably repeated instruction, both written and oral, provided by knowledgeable physicians is mandatory.

  19. Cell ATP level of Saccharomyces cerevisiae sensitively responds to culture growth and drug-inflicted variations in membrane integrity and PDR pump activity

    Czech Academy of Sciences Publication Activity Database

    Krasowska, A.; Lukaszewicz, M.; Bartosiewicz, D.; Sigler, Karel


    Roč. 395, č. 1 (2010), s. 51-55 ISSN 0006-291X R&D Projects: GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z50200510 Keywords : S. cerevisiae * ABC transporters * ATP level Subject RIV: EE - Microbiology, Virology Impact factor: 2.595, year: 2010

  20. PCR multiplexes discriminate Fusarium symbionts of invasive Euwallacea ambrosia beetles that inflict damage on numerous tree species throughout the United States (United States)

    Asian Euwallacea ambrosia beetles vector Fusarium mutualists. The ambrosial fusaria are all members of the Ambrosia Fusarium Clade (AFC) within the Fusarium solani species complex (FSSC). Several Euwallacea-Fusarium mutualists have been introduced into non-native regions and have caused varying degr...

  1. Selective vulnerability in brain hypoxia

    DEFF Research Database (Denmark)

    Cervos-Navarro, J.; Diemer, Nils Henrik


    Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis......Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis...

  2. Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease


    Vainshtein, A.; Veenman, L; Shterenberg, A; Singh, S; Masarwa, A; Dutta, B.; Island, B; Tsoglin, E; Levin, E.; Leschiner, S; Maniv, I; Pe?er, L; Otradnov, I; Zubedat, S; Aga-Mizrachi, S


    Expanding on a quinazoline scaffold, we developed tricyclic compounds with biological activity. These compounds bind to the 18?kDa translocator protein (TSPO) and protect U118MG (glioblastoma cell line of glial origin) cells from glutamate-induced cell death. Fascinating, they can induce neuronal differentiation of PC12 cells (cell line of pheochromocytoma origin with neuronal characteristics) known to display neuronal characteristics, including outgrowth of neurites, tubulin expression, and ...

  3. The developmental expression of fluorescent proteins in organotypic hippocampal slice cultures from transgenic mice and its use in the determination of excitotoxic neurodegeneration

    DEFF Research Database (Denmark)

    Noraberg, Jens; Jensen, Carsten V; Bonde, Christian


    in organotypic brain slice cultures, such as cellular uptake of propidium iodide (PI), loss of microtubule-associated protein 2 (MAP2), Fluoro-Jade (FJ) cell staining, and the release of cytosolic lactate dehydrogenase (LDH). An important supplement to these markers would be data on corresponding morphological......, including both the number and localisation of cells, as well as the intensity of fluorescence. At that stage and later, the transgenic fluorescence clearly permitted the visualisation of cell bodies, larger and smaller dendritic branches, spines and axons. In separate experiments, with a 24-hour exposure......Transgenic mice, expressing fluorescent proteins in neurons and glia, provide new opportunities for real-time microscopic monitoring of degenerative and regenerative structural changes. We have previously validated and compared a number of quantifiable markers for neuronal damage and cell death...

  4. Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

    Directory of Open Access Journals (Sweden)

    Babar E.


    Full Text Available The interactions between the median raphe nucleus (MRN serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 µg/side produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

  5. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Hardeep Kataria

    Full Text Available Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha, also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6 and human neuroblastoma (IMR-32 cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.

  6. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury (United States)


    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Novel Application of Stem Cell -Derived Neurons to Evaluate the Time- and Dose-Dependent 5a...01.10.RC.021). 14. ABSTRACT See reprint. 15. SUBJECT TERMS Mouse stem cell -derived neurons, NMDA receptor, AMPA receptor, Neurotoxicity, Apoptosis...area code) 410-436-8044 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Novel Application of Stem Cell -Derived Neurons to Evaluate the

  7. Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats. (United States)

    Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J


    The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

  8. Serial deletion reveals structural basis and stability for the core enzyme activity of human glutaminase 1 isoforms: relevance to excitotoxic neurodegeneration. (United States)

    Li, Yuju; Peer, Justin; Zhao, Runze; Xu, Yinghua; Wu, Beiqing; Wang, Yi; Tian, Changhai; Huang, Yunlong; Zheng, Jialin


    Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence. We have previously identified that KGA and GAC are differentially regulated during inflammatory stimulation and HIV infection. Furthermore, glutaminase 1 has been linked to brain diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and hepatic encephalopathy. Core enzyme structure of KGA and GAC has been published recently. However, how other coding sequences affect their functional enzyme activity remains unclear. We cloned and performed serial deletions of human full-length KGA and GAC from the N-terminal and the C-terminal at an interval of approximately 100 amino acids (AAs). Prokaryotic expressions of the mutant glutaminase 1 protein and a glutaminase enzyme activity assay were used to determine if KGA and GAC have similar efficiency and efficacy to convert glutamine into glutamate. When 110 AAs or 218 AAs were deleted from the N-terminal or when the unique portions of KGA and GAC that are beyond the 550 AA were deleted from the C-terminal, KGA and GAC retained enzyme activity comparable to the full length proteins. In contrast, deletion of 310 AAs or more from N-terminal or deletion of 450 AAs or more from C-terminal resulted in complete loss of enzyme activity for KGA/GAC. Consistently, when both N- and C-terminal of the KGA and GAC were removed, creating a truncated protein that expressed the central 219 AA - 550 AA, the protein retained enzyme activity. Furthermore, expression of the core 219 AA - 550 AA coding sequence in cells increased extracellular glutamate concentrations to levels comparable to those of full-length KGA and GAC expressions, suggesting that the core enzyme activity of the protein lies within the central 219 AA - 550 AA. Full-length KGA and GAC retained enzyme activities when kept at 4 °C. In contrast, 219 AA - 550 AA truncated protein lost glutaminase activities more readily compared with full-length KGA and GAC, suggesting that the N-terminal and C-terminal coding regions are required for the stability KGA and GAC. Glutaminase isoforms KGA and GAC have similar efficacy to catalyze the conversion of glutamine to glutamate. The core enzyme activity of glutaminase 1 protein is within the central 219 AA - 550 AA. The N-terminal and C-terminal coding regions of KGA and GAC help maintain the long-term activities of the enzymes.

  9. [{sup 18}F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Lavisse, S.; Inoue, K.; Jan, C.; Petit, F.; Dauguet, J.; Guillermier, M.; Rbah-Vidal, L.; Van Camp, N.; Aron-Badin, R.; Hantraye, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Peyronneau, M.A.; Goutal, S.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Remy, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Service de Neurologie, CHU Henri Mondor, Creteil (France)


    We aimed to characterize pharmacologically the TSPO- radioligand [{sup 18}F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). [{sup 18}F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V{sub T} (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [{sup 18}F]DPA-714 binding and microglial/astrocytic activation. [{sup 18}F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [{sup 18}F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V{sub T} and rate constants, and V{sub T} values from the 1-TCM and the Logan approach were highly correlated (r {sup 2} = 0.85). QA lesioning induced an increase in V{sub T}, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [{sup 18}F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. [{sup 18}F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain. (orig.)

  10. In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Butcher, S.P.; Lazarewicz, J.W.; Hamberger, A.


    The in vivo effects of kainate (1 mM) on fluxes of /sup 45/Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate /sup 45/Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate /sup 45/Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate-evoked alterations in either dialysate /sup 45/Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals.

  11. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens


    cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of alpha-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least...

  12. In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá


    PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a nov...... studies taking important experimental factors such as timing of treatment, dosage, and anesthesia into consideration....

  13. beta-amyloid excitotoxicity in rat magnocellular nucleus basalis - Effect of cortical deafferentation on cerebral blood flow regulation and implications for Alzheimer's disease

    NARCIS (Netherlands)

    Harkany, T.; Penke, B; Luiten, P.G.M.; Kalaria, RN; Ince, P


    Alzheimer's disease is the most common type of dementia with a still largely unclear etiopathology, One of the factors that may directly contribute to the development and progression of the disorder Is the abundant accumulation of beta-amyloid peptides (A beta) in senile plaques. In the present

  14. β-Amyloid Excitotoxicity in Rat Magnocellular Nucleus Basalis. Effect of Cortical Deafferentation on Cerebral Blood Flow Regulation and Implications for Alzheimer’s Disease

    NARCIS (Netherlands)

    Harkany, Tibor; Penke, Botond; Luiten, Paul G.M.


    Alzheimer’s disease is the most common type of dementia with a still largely unclear etiopathology. One of the factors that may directly contribute to the development and progression of the disorder is the abundant accumulation of β-amyloid peptides (Aβ) in senile plaques. In the present account we

  15. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bernardino, Liliana; Xapelli, Sara; Silva, Ana P


    The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of th...

  16. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C


    The potential toxic effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and its interactions with the N-methyl-D-aspartate (NMDA) receptor were studied in hippocampal brain slice cultures, using densitometric measurements of the cellular...... the PI uptake in both CA1 and CA3, compared to cultures exposed to 10 microM NMDA only. Adding the 300 microM ACPD as pretreatment for 30 min followed by a 30 min wash in normal medium before the ACPD/NMDA co-exposure, eliminated the potentiation of NMDA toxicity. The potentiation was also blocked...

  17. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity. (United States)

    Kataria, Hardeep; Wadhwa, Renu; Kaul, Sunil C; Kaur, Gurcharan


    Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.

  18. Protective Effects of Berberine on Oxygen-Glucose Deprivation/Reperfusion on Oligodendrocyte Cell Line (OLN-93

    Directory of Open Access Journals (Sweden)

    Shabnam Nadjafi


    Conclusions: We concluded that berberine protected OLN-93 oligodendrocyte against ischemic induced excitotoxic injury. Attenuation of intracellular Ca 2+ overload by berberine may be the key mechanism that saved OLN-93 from excitotoxicity damage.

  19. Inhibition of dopamine synthesis with alpha-methyl-p-tyrosine abolishes the enhancement of methamphetamine-induced extracellular dopamine levels in the amygdala of rats with excitotoxic lesions of the entorhinal cortex. (United States)

    Uehara, Takashi; Sumiyoshi, Tomiki; Itoh, Hiroko; Kurachi, Masayoshi


    This study was performed to investigate the mechanisms underlying the augmentation of methamphetamine (MAP)-induced dopamine (DA) release in the entorhinal cortex-lesioned rats. Quinolinic acid or phosphate buffered saline was infused into the left entorhinal cortex of adolescent rats (postnatal day 7 weeks). After 4 weeks of lesioning, acute MAP (2 mg/kg, i.p.)-induced DA release in the amygdala was significantly enhanced in lesioned rats compared to sham operated rats. Inhibition of DA synthesis by alpha-methyl-p-tyrosine, an inhibitor of catecholamine synthesis, resulted in abolishment of the enhancement of MAP (2 or 5 mg/kg, i.p.)-induced DA release in the amygdala of lesioned rats. These results suggest that excessive DA pool in nerve terminals underlies the augmentation of MAP-induced DA release in the amygdala of the lesioned rats.

  20. Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Christensen, Rasmus Kordt; Denti, Federico


    live imaging. We discovered that they are extraordinarily stable and exhibit a very low surface mobility both during steady state and neuronal stimulation. In the latter case, we also found that neither localization nor cell surface numbers were changed. However, at high glutamate loads, we observed......The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation. Therefore, changes in their localization or cell surface numbers are likely to influence neuronal signaling. However, nothing is known about...... the cell surface dynamics of Kv7.2/7.3 at steady state or during short-term neuronal stimulation. This is primarily attributable to their membrane topology, which hampers extracellular epitope tagging. Here we circumvent this limitation by fusing an extra phluorin-tagged helix to the N terminus of human Kv...

  1. Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression

    Energy Technology Data Exchange (ETDEWEB)

    Pozas, E. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain); Planas, A.M. [Departament de Farmacologia i Toxicologia, IIBB, CSIC Barcelona (Spain); Ferrer, I. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain)


    Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats.These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity of examining in detail the composition of c-Jun-immunoreactive bands and the metabolic state of c-Jun(s) in different paradigms of cell death and survival. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  2. Cytochrome c is released from mitochondria in a reactive oxygen species (ROS)-dependent fashion and can operate as a ROS scavenger and as a respiratory substrate in cerebellar neurons undergoing excitotoxic death. (United States)

    Atlante, A; Calissano, P; Bobba, A; Azzariti, A; Marra, E; Passarella, S


    In rat cerebellar granule cells both reactive oxygen species production and release of cytochrome c take place during glutamate toxicity. This investigation was aimed (i) to ascertain whether and how these two processes are related and (ii) to gain insight into the role played by the released cytochrome c in the onset of neurotoxicity. Cytochrome c release takes place owing to the generation of reactive oxygen species both in glutamate-treated cerebellar granule cells and in sister control cultures incubated in the presence of the reactive oxygen species-generating system consisting of xanthine plus xanthine oxidase. In the early phase of neurotoxicity (30-min glutamate exposure) about 40% of the maximum (as measured at 3 h of glutamate exposure) cytochrome c release was found to occur in cerebellar granule cells from mitochondria that were essentially coupled and intact and that had a negligible production of oxygen free radicals. Contrarily, mitochondria from cells treated with glutamate for 3 h were mostly uncoupled and produced reactive oxygen species at a high rate. The cytosolic fraction containing the released cytochrome c was able to transfer electrons from superoxide anion to molecular oxygen via the respiratory chain and was found to partially prevent glutamate toxicity when added externally to cerebellar neurons undergoing necrosis. In the light of these findings, we propose that in the early phase of neurotoxicity, cytochrome c release can be part of a cellular and mitochondrial defense mechanism against oxidative stress.

  3. Activation of Retinoid X Receptor increases dopamine cell survival in models for Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Bergsland Maria


    Full Text Available Abstract Background Parkinson's disease (PD is caused by degeneration of dopamine (DA neurons in the ventral midbrain (vMB and results in severely disturbed regulation of movement. The disease inflicts considerable suffering for the affected and their families. Today, the opportunities for pharmacological treatment are meager and new technologies are needed. Previous studies have indicated that activation of the nuclear receptor Retinoid X Receptor (RXR provides trophic support for DA neurons. Detailed investigations of these neurotrophic effects have been hampered by the lack of readily available DA neurons in vitro. The aim of this study was to further describe the potential neurotrophic actions of RXR ligands and, for this and future purposes, develop a suitable in vitro-platform using mouse embryonic stem cells (mESCs. Results We studied the potential neurotrophic effects of the RXR ligand LG100268 (LG268 and the RXR-Nurr1 ligand XCT0139508 (XCT in neuronal cultures derived from rat primary vMB and mESCs. RXR ligands protect DA neurons from stress, such as that induced by the PD-modeling toxin 6-hydroxy dopamine (6-OHDA and hypoxia, but not from stress induced by oxidative hydrogen peroxide (H2O2 or the excitotoxic agent kainic acid (KA. The neurotrophic effect is selective for DA neurons. DA neurons from rat primary vMB and mESCs behaved similarly, but the mESC-derived cultures contained a much higher fraction of DA cells and thus provided more accessible experimental conditions. Conclusions RXR ligands rescue DA neurons from degeneration caused by the PD simulating 6-OHDA as well as hypoxia. Thus, RXR is a novel promising target for PD research. mESC-derived DA cells provide a valid and accessible in vitro-platform for studying PD inducing toxins and potential trophic agents.

  4. Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion (United States)

    Reimer, Michell Mario; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Holland, Philip Robert; Smith, Jessica; Gliddon, Catherine; Wood, Emma R; Herzyk, Pawel; Brophy, Peter; McCulloch, James; Horsburgh, Karen


    Myelinated axons have a distinct protein architecture which is essential for action potential propagation, neuronal communication and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, is suggested to contribute to age-related cognitive decline. We sought to determine whether there are selective and early alterations in the protein architecture of myelinated axons in response to cerebral hypoperfusion. Using a mouse model of hypoperfusion we assessed changes in proteins, by confocal laser scanning microscopy, critical to the maintenance of the paranodes (contactin-associated protein (CASPR); Neurofascin155 (Nfasc155)), the nodes of Ranvier (voltage-gated sodium channels (Nav1.6), Neurofascin186 (Nfasc186) and AnkyrinG), axon-glial integrity (myelin-associated glycoprotein (MAG)), axon (SMI312) and myelin (myelin basic protein (MBP)). As early as 3 days after hypoperfusion, the paranodal septate-like junctions were damaged. This was marked by a progressive reduction of paranodal Neurofascin signal and a loss of septate-like junctions confirmed by electron microscopy. Concurrent with paranodal disruption there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Nfasc186 were unchanged and there were no changes in axonal and myelin integrity with hypoperfusion. Disruption of axon-glial integrity was also determined after hypoperfusion by changes in the spatial distribution of MAG staining. These nodal/paranodal changes were more pronounced after one month of hypoperfusion. A microarray analysis of white matter enriched samples of sham as compared with hypoperfused mice indicated that there were significant alterations in 129 genes (p<0.001). Subsequent enrichment analysis indicated alterations in biological pathways including inflammatory response, cytokine-cytokine receptor interaction, blood vessel development and cell

  5. A qualitative study on employees who have been inflicted by the adversity of continuous successful organizational change processes and downsizing in a key company now undergoing downsizing during a world economy in crisis: The effects of organizational rearrangements and downsizing in a key company


    Nesheim, Astrid K.


    This article addresses how the complexity of continual structural rearrangement within a key company impact employees. Data collection happened during a time of a world economy in crisis which seem be in the need of forcing new structural rearrangements and downsizing upon the local businesses. The sample is former and present employees who have experienced more than one structural rearrangement within the plant. Target information is the individual’s experiences and his/her recepti on and pe...

  6. Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures

    DEFF Research Database (Denmark)

    Penkowa, Milena; Florit, Sergi; Giralt, Mercedes


    We examined metallothionein (MT)-induced neuroprotection during kainic acid (KA)-induced excitotoxicity by studying transgenic mice with MT-I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed by inflammation and delayed brain damage. We show for th...

  7. The Effect of Age on the Susceptibility and Severity of Demyelination (United States)


    molecule known to mediate the connection of myelin to the axonal membrane known as neurofascin was a key factor in determining the susceptibility of...although the nodes are very evident in most of the field ( White arrows) , the paranodes (indicated by the red labelling) are virtually non- existent. In...injecting hormones so that she would ~ 12 ~ produce eggs removing the eggs and carrying out in vitro fertilization. The eggs are then implanted

  8. Protein 4.1B contributes to the organization of peripheral myelinated axons.

    Directory of Open Access Journals (Sweden)

    Carmen Cifuentes-Diaz

    Full Text Available Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.

  9. Protein 4.1B contributes to the organization of peripheral myelinated axons. (United States)

    Cifuentes-Diaz, Carmen; Chareyre, Fabrice; Garcia, Marta; Devaux, Jérôme; Carnaud, Michèle; Levasseur, Grégoire; Niwa-Kawakita, Michiko; Harroch, Sheila; Girault, Jean-Antoine; Giovannini, Marco; Goutebroze, Laurence


    Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.

  10. Lateral fluid percussion: model of traumatic brain injury in mice. (United States)

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita


    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

  11. Surveillance of Suicidal Behavior, January through December 2014 (United States)


    antisocial personality disorders . j Based on ICD-9 E-codes for self-inflicted injuries. k Based on ICD-9 V...borderline or antisocial personality disorders . m Based on ICD-9 E-codes for self-inflicted injuries. n Based on ICD-9 V-code for suicidal ideation... disorders . l Includes, for example, borderline or antisocial personality disorders . m Based on ICD-9 E-codes for self-inflicted injuries. n

  12. Consideration of Cosmetic Surgery As Part of Women’s Benefit-Provisioning Mate Retention Strategy

    National Research Council Canada - National Science Library

    Mohammad Atari; Nicole Barbaro; Yael Sela; Todd K. Shackelford; Razieh Chegeni


    .... We hypothesized that women’s consideration of cosmetic surgery would be positively associated with performance frequencies of Benefit-Provisioning and Cost-Inflicting mate retention behaviors...

  13. The combined incidence of Grade II and Grade IV astrocytoma in the ...

    African Journals Online (AJOL)

    capsaicin, piperine and monosodium glutamate, have excitotoxic, apoptotic or tumourigenic potentials. The focus of this histological study however, is to determine the tumourigenic potentials of Yaji in the brain of rats. Eight weeks old white ...

  14. Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes

    NARCIS (Netherlands)

    Aronica, E.; Catania, M. V.; Geurts, J.; Yankaya, B.; Troost, D.


    Excitotoxicity, which is mediated by the excessive activation of glutamate receptors, has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). There is substantial information about the distribution and function of ionotropic glutamate receptors in the spinal cord, although

  15. Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration

    DEFF Research Database (Denmark)

    Hansen, H.H.; Lastres-Becker, I.; Berrendero, F.


    Endogenous cannabinoid receptor ligands (endocannabinoids) may rescue neurons from glutamate excitotoxicity. As these substances also accumulate in cultured immature neurons following neuronal damage, elevated endocannabinoid concentrations may be interpreted as a putative neuroprotective respons...

  16. Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission

    DEFF Research Database (Denmark)

    Schousboe, A; Sarup, A; Bak, L K


    The fine tuning of both glutamatergic and GABAergic neurotransmission is to a large extent dependent upon optimal function of astrocytic transport processes. Thus, glutamate transport in astrocytes is mandatory to maintain extrasynaptic glutamate levels sufficiently low to prevent excitotoxic...

  17. Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus.


    Bunk, Eva C; König, Hans-Georg; Prehn, Jochen HM; Kirby, Brian P


    The N-methyl-D-aspartate (NMDA) receptor, one of the ionotropic glutamate receptor, plays important physiological and pathological roles in learning and memory, neuronal development, acute and chronic neurological diseases, and neurogenesis. This work examines the contribution of the NR2B NMDA receptor subunit to adult neurogenesis/cell proliferation under physiological conditions and following an excitotoxic insult. We have previously shown in vitro that a discrete NMDA-induced, excitotoxic ...

  18. Partial demyelination of cat spinal cord after x-irradiation and surgical interference

    Energy Technology Data Exchange (ETDEWEB)

    Blakemore, W.F.


    Following 4000 rad of x-irradiation and transplantation of sciatic nerve over the dorsal columns, extensive partial demyelination occurred in some animals. This dose of radiation inhibits remyelination so this phenomenon could be studied knowing that remyelination was absent. Partial demyelination was characterized by translocation of myelin to form large myelin ovoids which remained associated with the remaining thinned myelin sheath; nodal widening, involvement of one paranode only, transition from thin to thick myelin along an internode, enlargement and disorientated oligodendrocyte tongues were also features of this change. It is concluded that partial demyelination results when oligodendrocytes have to function in a sub-optimal environment.

  19. Notification ofpesticide poisoning in the western Cape, 1987 - 1991

    African Journals Online (AJOL)

    higher aInong those with self-inflicted injury, par- ticularly far= workers. A concurrent review of hospital .... (z) the poisoning was occupational, accidental or self- inflicted; and (zi) whether it occurred on a farm or at a .... worldwide realisation of the diversity of work-related disease and of the many different ways in which work.

  20. Enhanced wound contraction in fresh wounds dressed with honey in ...

    African Journals Online (AJOL)

    Background: Due to reports that honey accelerates wound healing, an investigation on its role in wound contraction in fresh wounds inflicted on wistar rats was carried out. Method: Twenty adult male wistar rats had 2cm by 2cm square wound inflicted on their right dorsolateral trunk. They were divided into two groups.

  1. Animal and Human Bites in Children | Osaghae | West African ...

    African Journals Online (AJOL)

    BACKGROUND: Mammals that live closely and interact with man and man himself can inflict injury on children in the home through bites. Previous reports on mammalian bites in Nigeria are few and mainly on dogs, though other mammals also inflict injuries on children. There are also no reports on the injuries arising from ...

  2. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy.

    Directory of Open Access Journals (Sweden)

    Kathrin Doppler

    Full Text Available Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.

  3. Early myelin breakdown following sural nerve crush: a freeze-fracture study

    Directory of Open Access Journals (Sweden)

    A.M.B. Martinez


    Full Text Available In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

  4. [Early reactive changes of myelin sheath in the area of myelin sheath gaps (nodes of Ranvier) in nerve fibers (a supravital study)]. (United States)

    Sotnikov, O S; Kokurina, T N; Solov'eva, I A; Sergeeva, S S


    Using the inverted phase contrast microscope, the supravital study of structural dynamics of single myelin sheath gaps (nodes of Ranvier) of isolated frog myelin nerve fibers was performed after mechanical injury and in the medium with the decreased ion force under the conditions which induce, in electrophysiological experiments, the expression of the axolemmal K+-channels in the paranodal area. Videorecording has shown that within this area the myelin sheath stratification appeared that was associated with the swelling of Schwann cell cytoplasm enclosed in the terminal membranous loops of myelin. An increase of the degree of stratification of the lamellar myelin complexes make them invisible in the light microscope; therefore, it is not the translocation of the myelin sheath from the node cleft that is recorded, as many authors believed, but a shift of only the visible border of the compact, yet unstratified myelin sheath. Hence, the removal of myelin (demyelination) was absent, and the electrophysiological effect can be accounted for by a significant fall of electrical resistance in paranodal area as a result of swelling of terminal loops and stratification of the myelin sheath. Preparations examination also revealed a decrease of the axonal diameter in, which is proportional to swelling of the myelin sheath terminal parts. Since the outer fiber diameter did not change, it can be concluded that the process observed is the result of swelling of the Schwann cell cytoplasm due to the axoplasm water fraction which may be a peculiar process of axo-glial interactions.

  5. The myelin sheath aqueous layers improve the membrane properties of simulated chronic demyelinating neuropathies. (United States)

    Stephanova, D I; Krustev, S M; Negrev, N; Daskalova, M


    Recently, patients with chronic demyelinating neuropathies have demonstrated significant abnormalities in their multiple nerve excitability properties measured by a non-invasive threshold tracking technique. In order to expand our studies on the possible mechanisms underlying these abnormalities, which are not yet well understood, we investigate the contributions of the aqueous layers within the myelin sheath on multiple membrane properties of simulated fibre demyelinations. Four degrees of systematic paranodal demyelinations (two mild demyelinations termed PSD1 and PSD2, without/with aqueous layers respectively, and two severe demyelinations termed PSD3 and PSD4, with/without aqueous layers, respectively) are simulated using our previous multi-layered model of human motor nerve fibre. We studied the following parameters of myelinated axonal function: potentials (intracellular action, electrotonic-reflecting the propagating and accommodative fibre processes, respectively) and strength-duration time constants, rheobases, recovery cycles (reflecting the adaptive fibre processes). The results show that each excitability parameter is markedly potentiated when the aqueous layers within their paranodally demyelinated sheaths are taken into account. The effect of the aqueous layers is significantly higher on the propagating processes than on the accommodative and adaptive processes in the fibres. The aqueous layers restore the action potential propagation, which is initially blocked when they are not taken into account. The study provides new and important information on the mechanisms of chronic demyelinating neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP). © Imperial College Press

  6. Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury. (United States)

    Calvo, Margarita; Richards, Natalie; Schmid, Annina B; Barroso, Alejandro; Zhu, Lan; Ivulic, Dinka; Zhu, Ning; Anwandter, Philipp; Bhat, Manzoor A; Court, Felipe A; McMahon, Stephen B; Bennett, David L H


    Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naïve state, showed increased expression within juxtaparanodes and paranodes following injury, both in rats and humans. Within the dorsal root (a site remote from injury) we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with α-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.

  7. Autoimmune antigenic targets at the node of Ranvier in demyelinating disorders. (United States)

    Stathopoulos, Panos; Alexopoulos, Harry; Dalakas, Marinos C


    Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.

  8. Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus. (United States)

    Bunk, E C; König, H-G; Prehn, J H M; Kirby, B P


    The N-methyl-D-aspartate (NMDA) receptor, one of the ionotropic glutamate receptor, plays important physiological and pathological roles in learning and memory, neuronal development, acute and chronic neurological diseases, and neurogenesis. This work examines the contribution of the NR2B NMDA receptor subunit to adult neurogenesis/cell proliferation under physiological conditions and following an excitotoxic insult. We have previously shown in vitro that a discrete NMDA-induced, excitotoxic injury to the hippocampus results in an increase in neurogenesis within the dentate gyrus. Here we have characterized adult neurogenesis or proliferation, using BrdU, in an in vivo model of excitotoxic injury to the CA1 subfield of the hippocampus. We demonstrate a peak in neural stem cell proliferation/neurogenesis between 6 and 9 days after the excitotoxic insult. Treatment with ifenprodil, an NR2B subunit-specific NMDA receptor antagonist, without prior injury induction, also increased the number of BrdU-positive cells within the DG and posterior periventricle, indicating that ifenprodil itself could modulate the rate of proliferation. Interestingly, though, the increased level of cell proliferation did not change significantly when ifenprodil was administered following an excitotoxic insult. In conclusion, our results suggest and add to the growing evidence that NR2B subunit-containing NMDA receptors play a role in neural stem cell proliferation. Copyright © 2014 Wiley Periodicals, Inc.

  9. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B


    -induced excitotoxicity and KA-glutamate receptor subunit mRNA expression after long-term exposure to low, non-toxic doses of KA and NBQX. We conclude that organotypic brain slice cultures, combined with standardized procedures for quantitation of cell damage and receptor subunit changes is of great potential use......Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation......-associated protein 2, and --e) general and specific neuronal and glial cell stains. The results show good correlation between the different markers, and are in accordance with results obtained in vivo. Examples presented in this review will focus on the use of PI uptake to monitor the excitotoxic effects of --a) KA...

  10. The neurotoxic mechanisms of amphetamine: Step by step for striatal dopamine depletion. (United States)

    Tung, Che-Se; Chang, Shang-Tang; Huang, Chuen-Lin; Huang, Nai-Kuei


    Amphetamine (AMPH) is a commonly abused psychostimulant that induces neuronal cell death/degeneration in humans and experimental animals. Although multiple neurotoxic mechanisms of AMPH have been intensively investigated, the interplay between these mechanisms has remained elusive. In this study, we used a rat model of AMPH-induced long-lasting striatal dopamine (DA) depletion and identified mechanisms of neurotoxicity, energy failure, excitotoxicity, and oxidative stress. Pretreatment with nicotinamide (NAM, a co-factor for the electron transport chain) blocked AMPH-induced free radical formation, energy failure, and striatal DA decrease. Also, MK-801 (a NMDA receptor antagonist) blocked AMPH-induced free radical formation and striatal DA but not energy failure decrease, indicating excitotoxicity may occur before free radical formation and after energy failure. Thus, these results show that during AMPH intoxication, energy failure, excitotoxicity, and free radical formation are orchestrated consecutively to mediate the depletion of striatal DA. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  11. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle Sønderby


    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux....

  12. On the neurotoxicity of glutaric, 3-hydroxyglutaric, and trans-glutaconic acids in glutaric acidemia type 1

    DEFF Research Database (Denmark)

    Lund, Trine Meldgaard; Christensen, E; Kristensen, A S


    Glutaric acidemia type 1 (GA1) is an autosomal recessively inherited deficiency of glutaryl-CoA dehydrogenase. Accumulating metabolites, 3-hydroxyglutaric (3-OH-GA), glutaric (GA), and trans-glutaconic (TG) acids, have been proposed to be involved in the development of the striatal degeneration...... seen in children with GA1 via an excitotoxic mechanism. We have studied the extent to which 3-OH-GA, GA, and TG are neurotoxic and whether neurotoxicity is caused by an excitotoxic mechanism in which 3-OH-GA, GA, or TG overactivates N-methyl-D-aspartate (NMDA) receptors. In cultured mouse neocortical...

  13. Axonal morphological changes following impulse activity in mouse peripheral nerve in vivo: the return pathway for sodium ions. (United States)

    Trigo, Diogo; Smith, Kenneth J


    Conduction in myelinated axons involves substantial ion movements that must be reversed to restore homeostasis. The pathway taken by sodium ions returning to their original location and the potential osmotic consequences are currently unknown. We report striking morphological changes in axons following sustained impulse conduction that appear to result from osmosis and to indicate accumulation of ions in the periaxonal space followed by their release at the paranode. We conclude that the morphological changes illustrate a hitherto unrecognized part of normal axonal physiology that may also indicate the return pathway for the sodium ions involved in impulse formation. Myelinated axons can conduct sustained trains of impulses at high frequency, but this involves substantial ion movements that must be reversed to restore homeostasis. Little attention has been paid to the potential osmotic consequences of the ion movements or to the pathway taken by sodium ions returning to their original endoneurial location, given that the axolemmal Na(+)-K(+)-ATPase extrudes these ions into the periaxonal space beneath the myelin rather than into the endoneurium. Serial confocal imaging of fluorescent axons conducting at sustained physiological frequencies in vivo has revealed surprising morphological changes that may illuminate these problems. Saphenous nerves and spinal roots of anaesthetized transgenic mice expressing axoplasmic yellow fluorescent protein were stimulated electrically or pharmacologically (veratridine). Within 2 h, the axon herniated on one or both sides of the nodal membrane, displacing the paranodal myelin and widening the nodal gap. The herniated axoplasm became directed back towards the internode, forming a 'cap' up to 30 μm long. Concurrently, the fluid in the expanded periaxonal space accumulated into droplets that appeared to travel to the paranode, where they escaped. No such alterations occurred in axons treated with sodium channel or Na

  14. Recent advances in marine microbiology: the Indian scenario

    Digital Repository Service at National Institute of Oceanography (India)

    Chandramohan, D.

    of protists, the thraustochytrids, in the marine environment has been elucidated. Fungal diseases inflicting local strains of algae, rock oysters and coral reefs have been highlighted. This review also covers aspects of shell-boring algae and fungi inhabiting...

  15. 25 CFR 11.1114 - Termination. (United States)


    ... by the parents or guardian of the child. The petition shall state: (1) The name, birth date, and... abandoned; (ii) The minor has suffered physical injuries, willfully and repeatedly inflicted by his or her...

  16. Untangling the neurobiology of escalated aggression in animals

    NARCIS (Netherlands)

    de Boer, Sietse F.

    Canines’ capacity for uncontrolled aggressiveness and violent-like behavior is a serious veterinary medicine concern and inflicts an awful burden on their owners. Unfortunately, the current intervention strategies and treatment options for curbing these problematic behavioral expressions are largely

  17. Synthesis of quarternary ammonium salts with dithiocarbamate ...

    Indian Academy of Sciences (India)

    ... dithiocarbamate moiety were synthesized and evaluated for their antifungal activities against Helminthosporium oryzae. All the synthesized compounds showed moderate to promising fungitoxicity against the test. Some of the synthesized compounds inflicted antifungal activity greater than the standard fungicide.

  18. Synthesis of quarternary ammonium salts with dithiocarbamate ...

    Indian Academy of Sciences (India)

    for their antifungal activities against Helminthosporium oryzae. All the synthesized compounds showed mode- rate to promising fungitoxicity against the test. Some of the synthesized compounds inflicted antifungal activity greater than the standard fungicide. Keywords. Dithiocarbamate; Helminthosporium oryzae; antifungal ...

  19. Eye Health in Sports and Recreation (United States)

    ... racquet sports, soccer and field hockey. Choose eye protectors that have been tested to meet the American ... health and preserving your vision. Privacy Policy Related Solar Eclipse Inflicts Damage in the Shape of the ...

  20. Environmental Enrichment, Performance, and Brain Injury in Male and Female Rats (United States)


    brain resulting from externally-inflicted trauma. Traumatic brain injuries principally result from vehicular incidents, falls, and sports injuries (NIH...neurodevelopmental disorders characterized by deficits in processing novel information (e.g., autism ). 141 Table 8. Summary of Major

  1. Skeletal imaging of child abuse (non-accidental injury)

    NARCIS (Netherlands)

    Offiah, A.; van Rijn, R.R.; Perez-Rossello, J.M.; Kleinman, P.K.


    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse

  2. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    NARCIS (Netherlands)

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.


    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for

  3. Veterinary Forensic Pathology of Animal Sexual Abuse

    National Research Council Canada - National Science Library

    Stern, A. W; Smith-Blackmore, M


    Animal sexual abuse (ASA) involves harm inflicted on animals for the purposes of human sexual gratification and includes such terms as bestiality, zoophilia, zoosadism, animal sexual assault, and others...

  4. Environmental impacts during the operational phase of residential buildings

    NARCIS (Netherlands)

    Blom, I.S.


    To date, the focus in the field of sustainable building has been on new building design. However, existing residential buildings inflict great environmental burden through three causes: continuous energy consumption, regular building maintenance and replacements. This publication analyses and

  5. Marine Attack on Towed Hydrophone Arrays

    National Research Council Canada - National Science Library

    Kalmijn, Ad


    The original objective of the SIO Marine Attack project was to identify the electric and magnetic fields causing sharks to inflict serious damage upon the towed hydrophone arrays of US Navy submarines...

  6. Shark Attack Project - Marine Attack at Towed Hydrophone Arrays

    National Research Council Canada - National Science Library

    Kalmijn, Adrianus J


    The original objective of the SIO Marine Attack project was to identify the electric and magnetic fields causing sharks to inflict serious damage upon the towed hydrophone arrays of US Navy submarines...

  7. [The establishment of the fact of the application of an electric circular saw with the high-speed reciprocating motion of the blade]. (United States)

    Nazarov, Iu V; Tolmachev, I A; Bozhchenko, A P


    This paper reports a case of forensic medical expertise of an unintentional (accidental) injury inflicted by an electric circular saw with the high-speed reciprocating motion of the blade (jigsaw) under conditions of human operational activities.

  8. An Overview of Female Genital Mutilation in Nigeria

    African Journals Online (AJOL)


    [2] FGM is an unhealthy traditional practice inflicted on girls and women worldwide. .... FGM varies from country to country, tribes, religion, and from one state and .... professional organizations, empowerment of the women in the society, and ...

  9. Genome of the Asian longhorned beetle, Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle-plant interface (United States)

    The Asian longhorned beetle (Anoplophora glabripennis; AGLAB) is a globally significant invasive species capable of inflicting severe feeding damage on many important orchard, ornamental and forest trees. Genome sequencing, annotation, gene expression assays, and functional and comparative genomic s...

  10. Hidradenitis Suppurativa/Acne Inversa

    DEFF Research Database (Denmark)

    Zouboulis, Christos C.; Del Marmol, Véronique; Mrowietz, Ulrich


    BACKGROUND: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating disease, which inflicts a significant burden on patients and is associated with comorbid disorders, such as significantly reduced quality of life, depression, stigmatization, inactivity...

  11. [The determination of the ballistics of a hunting rifle loaded with a Poleva-3 bullet]. (United States)

    Svetlakov, A V; Sotin, A V; Nagornov, M N


    Various approaches are considered to determine the shooting range of a hunting rifle loaded with a Poleva-3 bullet from the specific features of gunshot injuries inflicted by container-type Poleba-3 bullets for hunting rifles.

  12. Socioeconomic differences in injury risks in childhood and adolescence: a nation-wide study of intentional and unintentional injuries in Sweden

    DEFF Research Database (Denmark)

    Engström, K; Diderichsen, F; Laflamme, L


    , interpersonal violence, and self inflicted injuries. RESULTS: Injury incidences were relatively low and socioeconomic differences negligible in the 0-4 year olds. Thereafter, significant socioeconomic differences were observed in all diagnostic groups except falls. The highest absolute differences were...

  13. Transplant arteriosclerosis : an experimental study on risk factors and pathogenetic mechanisms

    NARCIS (Netherlands)

    Hillebrands, Jan Lucas


    In this thesis, we focused on vascular damage inflicted after transplantation, i.e. injury of the graft vasculature as a result of an alloreactive response of the host against the graft, and everal factors in-fluencing this process.

  14. Habitual biting of oral mucosa: A conservative treatment approach

    National Research Council Canada - National Science Library

    Bhatia, Sarabjot Kaur; Goyal, Ashima; Kapur, Aditi


    Chronic biting of oral mucosa is an innocuous self inflicted injury, commonly seen in children suffering from developmental and psychological problems and has rarely been reported in normal unaffected individuals...

  15. Analgesic effects of manual therapy in patients with musculoskeletal pain: a systematic review

    NARCIS (Netherlands)

    F. Struyf; J. Nijs; M. Meeys; D. Meuffels; J. de Vries; Dr. L.P. Voogt


    BACKGROUND: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic

  16. Research and Development of Wound Dressing in Maxillofacial Trauma. (United States)


    testing included Avitene testing by controlled bleeding of a dermatome -inflicted wound, and hemoglobin analysis of the dressing. PVP.1 2 fabric was...of a dermatome -inflicted wound, and hemoglobin analysis of the dressing. PVP-1 2 fabric was tested for bacteriostatic effectiveness using a iodine. 2. Avitene Evaluation The hemostatic evaluation of Avitene was proposed using a uniformly bleeding wound generated by a dermatome . The

  17. Habitual biting of oral mucosa: A conservative treatment approach

    Directory of Open Access Journals (Sweden)

    Sarabjot Kaur Bhatia


    Full Text Available Chronic biting of oral mucosa is an innocuous self inflicted injury, commonly seen in children suffering from developmental and psychological problems and has rarely been reported in normal unaffected individuals. The management strategies vary from counseling, prescription of sedatives to different prosthetic shields. The paper highlights the efficacy of a simple approach using soft mouth guard in the management of self inflicted lesions due to habitual biting of oral mucosa in two normal healthy children.

  18. Automutilation avec amputation de la verge chez des patients ...

    African Journals Online (AJOL)

    Les auteurs rapportent 2 cas d'automutilation avec dans un cas une plaie pénétrante de l'abdomen chez des patients schizophrènes. Mots Clés: Schizophrénie, Automutilation majeure, microchirurgie. Self-inflicted genital mutilation is a major self inflicted mutilation (MSM) and occurs rarely. Psychosis is a major factor of this ...

  19. Campylobacter jejuni DNA-binding protein from starved cells in Guillain-Barré syndrome patients. (United States)

    Kawamura, Nobutoshi; Piao, Hua; Minohara, Motozumi; Matsushita, Takuya; Kusunoki, Susumu; Matsumoto, Hiroshi; Ikenaka, Kazuhiro; Mizunoe, Yoshimitsu; Kira, Jun-ichi


    Campylobacter jejuni enteritis is frequently associated with an axonal form of Guillain-Barré syndrome (GBS) and C. jejuni DNA-binding protein from starved cells (C-Dps) induces paranodal myelin detachment and axonal degeneration through binding with sulfatide in vivo. Here we investigated the invasion of C-Dps into hosts with C. jejuni-related GBS. Our analyses of patient sera found that both C-Dps and anti-C-Dps antibodies were most commonly detected in sera from C. jejuni-related GBS patients (5/27, 14.8% and 15/24, 62.5%; respectively). These findings suggest that C-Dps invades the host and may potentially contribute to the peripheral nerve damage in C. jejuni-related GBS. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue (United States)

    Snaidero, Nicolas; Möbius, Wiebke; Czopka, Tim; Hekking, Liesbeth H.P.; Mathisen, Cliff; Verkleij, Dick; Goebbels, Sandra; Edgar, Julia; Merkler, Doron; Lyons, David A.; Nave, Klaus-Armin; Simons, Mikael


    Summary Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels are closing with ongoing development, but can be re-opened in adult by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life. PMID:24439382

  1. Computational modeling of the effects of auditory nerve dysmyelination

    Directory of Open Access Journals (Sweden)

    Angus M Brown


    Full Text Available Our previous study showed that exposure to loud sound leading to hearing loss elongated the auditory nerve nodes of Ranvier and triggered notable morphological changes at paranodes and juxtaparanodes. Here we used computational modeling to examine how theoretical redistribution of voltage gated Na+, Kv3.1 and Kv1.1 channels along the auditory nerve may be responsible for the alterations of conduction property following acoustic over-exposure. Our modeling study infers that changes related to Na+ channel density (rather than the redistribution of voltage gated Na+, Kv3.1 and Kv1.1 channels is the likely cause of the decreased conduction velocity and the conduction block observed after acoustic overexposure.

  2. Lewis-Sumner syndrome and Tangier disease. (United States)

    Théaudin, Marie; Couvert, Philippe; Fournier, Emmanuel; Bouige, Daniel; Bruckert, Eric; Perrotte, Paul; Vaschalde, Yvan; Maisonobe, Thierry; Bonnefont-Rousselot, Dominique; Carrié, Alain; Le Forestier, Nadine


    To report unusual electrophysiologic data in a patient with Tangier disease in an effort to better understand the pathophysiologic features of the peripheral nerve lesions in this disease. Case report. A 15-year-old girl had subacute onset of asymmetric neuropathy with persistent conduction block, resembling Lewis-Sumner syndrome. Electrophysiologic data in Tangier disease. After initially unsuccessful treatment with intravenously administered immunoglobulins, the finding of an abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1) (OMIM 9q22-q31). Conduction block, which is the electrophysiologic hallmark of focal demyelination, can be present in Tangier disease. It could be induced by focal nerve ischemia or by preferential lipid deposition in the paranodal regions of myelinated Schwann cells. The presence of a conduction block in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.

  3. Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy. (United States)

    Child, Nicholas D; Benarroch, Eduardo E


    Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

  4. A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc− Mediates Aglycemic Neuronal Cell Death

    Directory of Open Access Journals (Sweden)

    Trista L. Thorn


    Full Text Available The astrocyte cystine/glutamate antiporter (system xc− contributes substantially to the excitotoxic neuronal cell death facilitated by glucose deprivation. The purpose of this study was to determine the mechanism by which this occurred. Using pure astrocyte cultures, as well as, mixed cortical cell cultures containing both neurons and astrocytes, we found that neither an enhancement in system xc− expression nor activity underlies the excitotoxic effects of aglycemia. In addition, using three separate bioassays, we demonstrate no change in the ability of glucose-deprived astrocytes—either cultured alone or with neurons—to remove glutamate from the extracellular space. Instead, we demonstrate that glucose-deprived cultures are 2 to 3 times more sensitive to the killing effects of glutamate or N-methyl-D-aspartate when compared with their glucose-containing controls. Hence, our results are consistent with the weak excitotoxic hypothesis such that a bioenergetic deficiency, which is measureable in our mixed but not astrocyte cultures, allows normally innocuous concentrations of glutamate to become excitotoxic. Adding to the burgeoning literature detailing the contribution of astrocytes to neuronal injury, we conclude that under our experimental paradigm, a cytotoxic, co-operative interaction between energy deprivation and glutamate release from astrocyte system xc− mediates aglycemic neuronal cell death.

  5. Pretreatment with Lovastatin Prevents N-Methyl-D-Aspartate-Induced Neurodegeneration in the Magnocellular Nucleus Basalis and Behavioral Dysfunction

    NARCIS (Netherlands)

    Dolga, Amalia; Granic, Ivica; Nijholt, Ingrid M.; Nyakas, Csaba; van der Zee, Eddy A.; Luiten, Paul G. M.; Eisel, Ulrich L. M.; Bierhaus, Angelika


    Besides a beneficial cardiovascular effect, it was recently suggested that statins can also exert neuroprotective actions. In a previous study, we provided in vitro evidence that lovastatin treatment abates excitotoxic cell death in primary cortical neurons. Here, we investigated the neuroprotective

  6. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding. (United States)

    Nakamura, T; Lipton, S A


    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity.

  7. Characterisation of a Cell Culture System for Investigating Nerve Agent Neurotoxicology. Part 1 (United States)


    massive release of excitatory neurotransmitters, such as glutamate , which over-stimulate their receptors resulting in excitotoxicity and brain damage...Shapira et al., 2000). The occurrence of SNPs in the AChE coding region in people with different ethnic backgrounds has been studied with 15 haplotypes

  8. Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure (United States)


    traumatic memories, or dissociating the emotional response from the traumatic memory. 49 The N-methyl-D-aspartate (NMDA) glutamate receptors play a...gender, race, ethnicity and age appear to have minimal if any effects on antidepressant response. 165 However, living with a significant other...peroxidation, 192 improving mitochondrial function, 191 blocking excitotoxic effects of glutamate and other excitatory amino acid neurotransmitters

  9. Download this PDF file

    African Journals Online (AJOL)

    Children Undergoing Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 22(7):. 1264-1270. 2. Mummedy, S., Wan, N., Wan, A. (2014). Restoration of glutamine synthetase activity, nitric oxide levels and amelioration of oxidative stress by propolis in kainic acid mediated excitotoxicity.

  10. Molecular complexity of primary open angle glaucoma: current ...

    Indian Academy of Sciences (India)

    Current concepts of glaucoma pathogenesis suggest it to be a neurodegenerative disorder which is triggered by different factors including mechanical stress due to intra-ocular pressure, reduced blood flow to retina, reperfusion injury, oxidative stress, glutamate excitotoxicity, and aberrant immune response. Here we ...

  11. Glutamate Efflux at the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Cederberg-Helms, Hans Christian; Uhd-Nielsen, Carsten; Brodin, Birger


    L-Glutamate is considered the most important excitatory amino acid in the mammalian brain. Strict control of its concentration in the brain interstitial fluid is important to maintain neurotransmission and avoid excitotoxicity. The role of astrocytes in handling L-glutamate transport and metaboli...

  12. Anterograde and Retrograde Amnesia of Place Discrimination in Retrosplenial Cortex and Hippocampal Lesioned Rats (United States)

    Haijima, Asahi; Ichitani, Yukio


    Retrograde and anterograde amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) were investigated. To test retrograde amnesia, rats were trained with two-arm place discrimination in a radial maze 4 wk and 1 d before surgery with a different arm pair, respectively. In the retention test 1 wk after…

  13. Propolis Ameliorates Tumor Nerosis Factor-α, Nitric Oxide levels ...

    African Journals Online (AJOL)

    Background: Increased nitric oxide (NO), neuronal inflammation and apoptosis have been proposed to be involved in excitotoxicity plays a part in many neurodegenerative diseases. To understand the neuro-protective effects of propolis, activities of Nitric oxide synthase (NOS) and caspase-3 along with NO and tumor ...

  14. Phenolic antioxidants attenuate hippocampal neuronal cell damage ...

    Indian Academy of Sciences (India)


    toxicity; J. Biosci. 28 121–128]. 1. Introduction. Excitotoxicity is a contributing factor to the pathogenesis of neurodegenerative disorders such as Alzheimer's dis- ease (Law et al 2001) and Parkinson's disease (Beal. 1995; Hantraye et al 1996). Although each disease has distinctive morphological and biochemical characteri-.

  15. Targeting Mitochondria by Olesoxime or Complement 1q Binding Protein as a Novel Management for Autism: A Hypothesis


    Ghanizadeh, A.


    Excitotoxicity, oxidative stress, and mitochondrial dysfunction are associated with autism. Considering the preventive role of complement 1q binding protein or olesoxime for the opening of mitochondrial permeability transition pore mediated by oxidative stress, it is hypothesized that complement 1q binding protein or olesoxime may improve some symptoms of autism.

  16. The Neuroprotective Peptide Poly-Arginine-12 (R12) Reduces Cell Surface Levels of NMDA NR2B Receptor Subunit in Cortical Neurons; Investigation into the Involvement of Endocytic Mechanisms. (United States)

    MacDougall, Gabriella; Anderton, Ryan S; Edwards, Adam B; Knuckey, Neville W; Meloni, Bruno P


    We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx. Using cell surface biotin protein labeling and western blot analysis, we demonstrated that R12 and TAT-NR2B9c significantly reduced cortical neuronal cell surface expression of the NMDA receptor subunit NR2B. Chemical endocytic inhibitors used individually or in combination prior to glutamate excitotoxicity did not significantly affect R12 peptide neuroprotective efficacy. Similarly, pretreatment of neurons with enzymes to degrade anionic cell surface proteoglycans, heparan sulfate proteoglycan (HSPG), and chondroitin sulfate proteoglycan (CSPG), as well as sialic acid residues, did not significantly affect peptide neuroprotective efficacy. While the exact mechanisms responsible for R12 peptide-mediated NMDA receptor NR2B subunit cell surface downregulation were not identified, an endocytic process could not be ruled out. The study supports our hypothesis that arginine-rich peptides reduce excitotoxic calcium influx by reducing the levels of cell surface ion channels.

  17. Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation

    NARCIS (Netherlands)

    Hilker, R; Portman, AT; Voges, J; Staal, MJ; Burghaus, L; van Laar, T; Koulousakis, A; Maguire, RP; Pruim, J; de Jong, BM; Herholz, K; Sturm, [No Value; Heiss, WD; Leenders, KL

    Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications,

  18. Oral post-lesion administration of 5-HT1A receptor agonist repinotan hydrochloride (Bay X 3702) attenuates NMDA-induced delayed neuronal death in rat magnocellular nucleus basalis

    NARCIS (Netherlands)

    Harkany, T.; Mulder, Jan; Horvath, K.M.; Keijser, Johannes; Meeberg, E.K. van der; Nyakas, C.; Luiten, P.G.M.


    Recent evidence indicates that stimulation of postsynaptic 5-HT1A receptors abates excitotoxic neuronal death. Here we investigated whether oral post-lesion administration of the 5-HT1A receptor agonist (-)-(R)-2-[4-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]butyl]-1,2-benzisothiazol-3(2H)-one

  19. African Journal of Traditional, Complementary and Alternative ...

    African Journals Online (AJOL)

    Anti-Hyperglycemic And Anti-Hyperlipidemic Potential Of A Polyherbal Preparation “Diabegon” In Metabolic Syndrome Subject With Type 2 Diabetes · EMAIL FREE .... Restoration Of Glutamine Synthetase Activity, Nitric Oxide Levels And Amelioration Of Oxidative Stress By Propolis In Kainic Acid Mediated Excitotoxicity ...

  20. Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium (United States)


    increase the risk of CNS diseases such as epilepsy or those thought to possess an excitotoxic component (Huntington’s, amyotrophic lateral sclerosis ...the left side of Figure 5. As a result of the data in Figures 4 and 5 two observations are apparent. First, the enhancement of evoked

  1. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

    DEFF Research Database (Denmark)

    Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin


    During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons ...... suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets....

  2. The Regulation of Endogenous Glutamate and GABA Release from In Vitro Preparations of Rat Striatum (United States)


    Butcher SP~ JW Lazarewicz and A Hamberger, In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced...striatum and cerebral cortex of guinea pig and rat. Neurosci. 31 (1989). 313-25. Lapper SR and JP Bolam. Input from the frontal cortex and the papafascicuIar

  3. Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells


    Garcia-Martinez, Eva Maria; Sanz-Blasco, Sara; Karachitos, Andonis; Bandez, Miguel J.; Fernandez-Gomez, Francisco J; Perez-Alvarez, Sergio; Mera, Raquel Maria Melero Fernandez De; Jordan, Maria J.; Aguirre, Norberto; Galindo, Maria F.; Villalobos, Carlos; Navarro, Ana; Kmita, Hanna; Jordán, Joaquín


    Abstract Minocycline, an antibiotic of the tetracycline family, has attracted considerable interest for its theoretical therapeutic applications in neurodegenerative diseases. However, the mechanism of action underlying its effect remains elusive. Here we have studied the effect of minocycline under excitotoxic conditions. Fluorescence and bioluminescence imaging studies in rat cerebellar granular neuron cultures using fura-2/AM and mitochondria-targeted aequorin revealed that mino...

  4. Adaptive plasticity during stress and depression and the role of ...

    African Journals Online (AJOL)

    Stress in various guises may alter synaptic connectivity in the brain by bolstering glutamatergic excitotoxic mechanisms. Understanding these mechanisms may assist in developing more effective treatment strategies. This paper will review pre-clinical and clinical evidence supporting a role for the glutamatenitric oxide ...

  5. The influence of cannabinoids on generic traits of neurodegeneration


    Fagan, S G; Campbell, V A


    In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay ...

  6. Inhibition of Calpain Prevents N-Methyl-D-aspartate-Induced Degeneration of the Nucleus Basalis and Associated Behavioral Dysfunction

    NARCIS (Netherlands)

    Nimmrich, Volker; Szabo, Robert; Nyakas, Csaba; Granic, Ivica; Reymann, Klaus G.; Schroeder, Ulrich H.; Gross, Gerhard; Schoemaker, Hans; Wicke, Karsten; Moeller, Achim; Luiten, Paul


    N-Methyl-D-aspartate( NMDA) receptor-mediated excitotoxicity is thought to underlie a variety of neurological disorders, and inhibition of either the NMDA receptor itself, or molecules of the intracellular cascade, may attenuate neurodegeneration in these diseases. Calpain, a calcium-dependent

  7. In vivo protection against NMDA-induced neurodegeneration by MK-801 and nimodipine : Combined therapy and temporal course of protection

    NARCIS (Netherlands)

    Stuiver, BT; Douma, BRK; Bakker, R; Nyakas, C; Luiten, PGM

    Neuroprotection against excitotoxicity by a combined therapy with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the L-type Ca2+ channel blocker nimodipine was examined using an in vivo rat model of NMDA-induced neurodegeneration. Attention was focused on the neuroprotective

  8. beta-amyloid((1-42))-induced cholinergic lesions in rat nucleus basalis bidirectionally modulate serotonergic innervation of the basal forebrain and cerebral cortex

    NARCIS (Netherlands)

    Harkany, T; O'Mahony, S; Kelly, JP; Konya, C; Borostyankoi, ZA; Gorcs, TJ; Zarandi, M; Penke, B; Leonard, BE; Luiten, PGM; Keijser, Jan N.

    Ample experimental evidence suggests that beta -amyloid (A beta), when injected into the rat magnocellular nucleus basalis (MBN), impels excitotoxic injury of cholinergic projection neurons. Whereas learning and memory dysfunction is a hallmark of A beta -induced cholinergic deficits, anxiety, or

  9. Author Details

    African Journals Online (AJOL)

    Restoration Of Glutamine Synthetase Activity, Nitric Oxide Levels And Amelioration Of Oxidative Stress By Propolis In Kainic Acid Mediated Excitotoxicity Abstract PDF · Vol 11, No 5 (2014) - Articles Propolis Ameliorates Tumor Nerosis Factor-α, Nitric Oxide levels, Caspase-3 and Nitric Oxide Synthase Activities in Kainic ...

  10. Author Details

    African Journals Online (AJOL)

    Norlina, W. Vol 11, No 2 (2014) - Articles Restoration Of Glutamine Synthetase Activity, Nitric Oxide Levels And Amelioration Of Oxidative Stress By Propolis In Kainic Acid Mediated Excitotoxicity Abstract PDF. ISSN: 0189-6016. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  11. Towards gene therapy in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wisman, Liselijn Agatha Barendina


    Amyotrophic lateral sclerosis (ALS) is a paralytic neurodegenerative disorder, characterised by a specific loss of motoneurons. Although the exact pathogenesis is largely enigmatic, it is known that glutamate excitotoxicity plays an important role in motoneuron cell death. Glutamate is one of the

  12. Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis

    NARCIS (Netherlands)

    Al-Izki, S.; Pryce, G.; Hankey, D.J.R.; Lidster, K.; von Kutzleben, S.M.; Browne, L.; Clutterbuck, L.; Posada, C.; Chan, A.W.E.; Amor, S.; Perkins, V.; Gerritsen, W.H.; Ummenthum, K.; Peferoen-Baert, R.; van der Valk, P.; Montoya, A.; Joel, S.P.; Garthwaite, J.; Giovannoni, G.; Selwood, D.L.; Baker, D.


    Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to

  13. Acute Administration of Methionine Affects Performance of Swiss ...

    African Journals Online (AJOL)


    Similarly, chronic blood homocysteine (HCY) levels have also been shown to cause adult neurological disorders by excitotoxicity and generation of reactive oxygen species (ROS) (Louisa,. 2004). Central cholinergic system plays a major role in regulation of cognitive functions and inhibition of acetylcholinesterase leads to ...

  14. N-methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against beta-amyloid neurotoxicity

    NARCIS (Netherlands)

    Harkany, T.; Mulder, J.; Sasvari, M.; Abraham, I.; Konya, C.; Zarandi, M.; Penke, B; Luiten, P.G.M.; Nyakas, C.

    Previous experimental data indicate the involvement of Ca2+-related excitotoxic processes, possibly mediated by N-Methyl-D-Aspartate (NMDA) receptors, in beta-amyloid (beta A) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step

  15. Histological effects of chronic administration of Phyllanthus amarus ...

    African Journals Online (AJOL)



    Jun 21, 2010 ... role in certain aspects of vision. Its major role is to co- ordinate responses evoked by a variety of sensory signals with behavioural movements .... Neurodegeneration in excitotoxicity, global cerebral ischaemia and target Deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res.

  16. GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia

    Directory of Open Access Journals (Sweden)

    Y.P. Zhang


    Full Text Available White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD. Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155, and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1 on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group. HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05 and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05. Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties.

  17. Complement deposition induced by binding of anti-contactin-1 auto-antibodies is modified by immunoglobulins. (United States)

    Appeltshauser, Luise; Weishaupt, Andreas; Sommer, Claudia; Doppler, Kathrin


    Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3. We therefore aimed to investigate complement deposition and activation by samples of three patients with anti-contactin-1 IgG auto-antibodies of different subclasses as a potential predictor for response to IVIG. Complement deposition and activation was measured by cell binding and ELISA based assays, and the effect of IVIG on complement deposition was assessed by addition of different concentrations of IVIG. Binding of anti-contactin-1 auto-antibodies of all three patients induced complement deposition and activation with the strongest effect shown by the serum of a patient with predominance of IgG3 auto-antibodies. IVIG led to a reduction of complement deposition in a dose-dependent manner, but did not reduce binding of auto-antibodies to contactin-1. We conclude that complement deposition may contribute to the pathophysiology of anti-contactin-1 associated neuropathy, particularly in patients with predominance of the IgG3 subclass. The proportion of different auto-antibody subclasses may be a predictor for the response to IVIG in patients with auto-antibodies against paranodal proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Nicotinic receptors modulate the onset of reactive oxygen species production and mitochondrial dysfunction evoked by glutamate uptake block in the rat hypoglossal nucleus. (United States)

    Tortora, Maria; Corsini, Silvia; Nistri, Andrea


    In several neurodegenerative diseases, glutamate-mediated excitotoxicity is considered to be a major process to initiate cell degeneration. Indeed, subsequent to excessive glutamate receptor stimulation, reactive oxygen species (ROS) generation and mitochondrial dysfunction are regarded as two major gateways leading to neuron death. These processes are mimicked in an in vitro model of rat brainstem slice when excitotoxicity is induced by DL-threo-β-benzyloxyaspartate (TBOA), a specific glutamate-uptake blocker that increases extracellular glutamate. Our recent study has demonstrated that brainstem hypoglossal motoneurons, which are very vulnerable to this damage, were neuroprotected from excitotoxicity with nicotine application through the activation of nicotinic acetylcholine receptors (nAChRs) and subsequent inhibition of ROS and mitochondrial dysfunction. The present study examined if endogenous cholinergic activity exerted any protective effect in this pathophysiological model and how ROS production (estimated with rhodamine fluorescence) and mitochondrial dysfunction (measured as methyltetrazolium reduction) were time-related during the early phase of excitotoxicity (0-4h). nAChR antagonists did not modify TBOA-evoked ROS production (that was nearly doubled over control) or mitochondrial impairment (25% decline), suggesting that intrinsic nAChR activity was insufficient to contrast excitotoxicity and needed further stimulation with nicotine to become effective. ROS production always preceded mitochondrial dysfunction by about 2h. Nicotine prevented both ROS production and mitochondrial metabolic depression with a delayed action that alluded to a complex chain of events targeting these two lesional processes. The present data indicate a relatively wide time frame during which strong nAChR activation can arrest a runaway neurotoxic process leading to cell death. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. It's agony for us as well: Neonatal nurses reflect on iatrogenic pain. (United States)

    Green, Janet; Darbyshire, Philip; Adams, Anne; Jackson, Debra


    Improved techniques and life sustaining technology in the neonatal intensive care unit have resulted in an increased probability of survival for extremely premature babies. The by-product of the aggressive treatment is iatrogenic pain, and this infliction of pain can be a cause of suffering and distress for both baby and nurse. The research sought to explore the caregiving dilemmas of neonatal nurses when caring for extremely premature babies. This article aims to explore the issues arising for neonatal nurses when they inflict iatrogenic pain on the most vulnerable of human beings - babies ≤24 weeks gestation. Data were collected via a questionnaire to Australian neonatal nurses and semi-structured interviews with 24 neonatal nurses in New South Wales, Australia. Ethical processes and procedures set out by the ethics committee have been adhered to by the researchers. A qualitative approach was used to analyse the data. The theme 'inflicting pain' comprised three sub-themes: 'when caring and torture are the same thing', 'why are we doing this!' and 'comfort for baby and nurse'. The results show that the neonatal nurses were passionate about the need for appropriate pain relief for extremely premature babies. The neonatal nurses experienced a profound sense of distress manifested as existential suffering when they inflicted pain on extremely premature babies. Inflicting pain rather than relieving it can leave the nurses questioning their role as compassionate healthcare professionals. © The Author(s) 2014.

  20. Diagnostic imaging of child abuse

    Energy Technology Data Exchange (ETDEWEB)

    Oguma, Eiji; Aihara, Toshinori [Saitama Children' s Medical Center, Iwatsuki (Japan)


    The major role of imaging in cases of suspected child abuse is to identify the physical injuries and to confirm the occurrence of abuse. In severely abused infants, the imaging findings may be the only evidence for a diagnosis of inflicted injury. Imaging may be the first clue to abuse in children seen with apparent other conditions and lead to appropriate measures to protect them from the risk of more serious injury. The radiologist must be familiar with imaging findings of inflicted injuries to fulfill these roles. (author)

  1. Vellykket konservativ behandling efter knivtraume mod hjertet

    DEFF Research Database (Denmark)

    Wærsted, Stian; Schou-Jensen, Katrine; Jensen, Tim


    A five year-old girl was admitted to hospital following an accidental stab wound to the chest, inflicted by a knife placed in a dishwasher's cutlery tray. Investigations revealed a traumatic ventricular septum defect of the heart, with a pericardial effusion. Since the patient remained haemodynam......A five year-old girl was admitted to hospital following an accidental stab wound to the chest, inflicted by a knife placed in a dishwasher's cutlery tray. Investigations revealed a traumatic ventricular septum defect of the heart, with a pericardial effusion. Since the patient remained...

  2. Sharp force injuries in "clinical" forensic medicine. (United States)

    Schmidt, Ulrike


    In general, the forensic evaluation of sharp force injuries in living and dead individuals follows the same morphologic principles. Still, there are some special features of sharp force injuries in the clinical context, which have to be considered as examination findings on the living are interpreted to differentiate between accidental origin, self-infliction or homicidal assault. These include the frequency and localization of defence injuries, injuries of the perpetrator, and artificial injuries, especially those inflicted for the purpose of insurance fraud. Characteristics and differential diagnoses of "clinical" sharp force injuries are surveyed in this article. 2009 Elsevier Ireland Ltd. All rights reserved.

  3. الجزاءات الإدارية: بين ضرورات الفعالية الإدارية وقيود حماية الحقوق والحريات الأساسية -دراسة مقارنة -

    Directory of Open Access Journals (Sweden)

    صلاح الدين بوجلال


    Full Text Available in each system of law, the administrative sanctions take a distinct place along the criminal and civil sanctions. Administrative sanctions are inflicted by administrative bodies to ensure the fulfillment of certain obligations or restoring some legal conditions, such as withdrawing, suspending or denial of an advantage or facility provided by law. The punitive character of these sanctions required the applicability of some law principles from the criminal law into the administrative law, to ensure the protection against abuse in inflicting a punitive sanction, and also guarantees for each person the right to a fair trial.

  4. Parental social determinants of risk for intentional injury: a cross-sectional study of Swedish adolescents

    DEFF Research Database (Denmark)

    Engström, Karin; Diderichsen, Finn; Laflamme, Lucie


    in the household (1- or 2-parent home), receipt of welfare benefits, parental country of birth, and population density as exposures and compiled relative risks and population-attributable risks (PARs) for self-inflicted and interpersonal violence-related injury. RESULTS: For both genders and for both injury types......, receipt of welfare benefits showed the largest crude and net relative risks and the highest PARs. The socioeconomic status-related PAR for self-inflicted injury and the PAR related to number of parents in the household for interpersonal violence-related injury also were high. CONCLUSIONS: Intentional...

  5. Extreme Rituals as Social Technologies

    DEFF Research Database (Denmark)

    Fischer, Ronald; Xygalatas, Dimitris


    We often think of pain as intrinsically bad, and the avoidance of pain is a fundamental evolutionary drive of all species. How can we then explain widespread cultural prac- tices like certain rituals that involve the voluntary infliction of physical pain? In this paper, we argue that inflicting...... and experiencing pain in a ritual setting may serve important psychological and social functions. By providing psychological relief and leading to stronger identification with the group, such practices may result in a positive feedback loop, which serves both to increase the social cohesion of the community...

  6. The impact of force on the timing of bruises evaluated in a porcine model

    DEFF Research Database (Denmark)

    Barington, Kristiane; Jensen, Henrik Elvang


    kept in anesthesia for 2, 4, 6 or 8 h, after which they were euthanized, and skin and muscle tissues were sampled for histology. As control, two pigs were included. The gross appearance of bruises developed similarly until 0.5 h after infliction at which time the visibility of the bruises depended...... on the force. The infiltration of subcutaneous neutrophils depended on the time and force used which was confirmed by both manual evaluation and image analysis of immunostained skin sections. In the muscle tissue, the number of macrophages was found useful for age determination in bruises inflicted...

  7. Protective effect of naringenin on glutamate-induced neurotoxicity in cultured hippocampal cells

    Directory of Open Access Journals (Sweden)

    Xu Xiao-Hui


    Full Text Available Monosodium glutamate induces excitotoxicity in the central nervous system through hyperactivation of both ionotropic and metabotropic glutamate receptors, which leads to neuronal cell death. In this study, we investigated the neuroprotective effects of naringenin on excitotoxicity induced by glutamate in primary hippocampal neurons of neonatal mice. The expression levels of apoptosis-inducing proteins and as well as ischemic factors were observed by Western blot analysis. Immunocytochemistry and morphometric analysis of hippocampal cells with or without glutamate and naringenin treatment were performed. We observed that naringenin regulated Erk1/2 and Akt phosphorylation and reduced the demise of dendrites due to glutamate exposure in cultured hippocampal neurons. Furthermore, naringenin induced the brain-derived neurotrophic factor and other neuroprotective cytokines, and markedly improved the survival rates of the neurons 24 h following glutamate exposure. The observed results suggest that the naturally occurring bioflavonoid (naringenin exerts neuroprotective effects via highly specific molecular targets in neurons.

  8. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo. (United States)

    Rashidian, Juliet; Iyirhiaro, Grace; Aleyasin, Hossein; Rios, Mario; Vincent, Inez; Callaghan, Steven; Bland, Ross J; Slack, Ruth S; During, Matthew J; Park, David S


    The mechanisms involving neuronal death after ischemic/hypoxic insult are complex, involving both rapid (excitotoxic) and delayed (apoptotic-like) processes. Recent evidence suggests that cell cycle regulators such as cyclin-dependent kinases are abnormally activated in neuropathological conditions, including stroke. However, the function of this activation is unclear. Here, we provide evidence that inhibition of the cell cycle regulator, Cdk4, and its activator, cyclinD1, plays critical roles in the delayed death component of ischemic/hypoxic stress by regulating the tumor suppressor retinoblastoma protein. In contrast, the excitotoxic component of ischemia/hypoxia is predominately regulated by Cdk5 and its activator p35, components of a cyclin-dependent kinase complex associated with neuronal development. Hence, our data both characterize the functional significance of the cell cycle Cdk4 and neuronal Cdk5 signals as well as define the pathways and circumstances by which they act to control ischemic/hypoxic damage.

  9. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez


    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  10. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study. (United States)

    Yablonsky-Alter, Elena; Agovic, Mervan S; Gashi, Eleonora; Lidsky, Theodore I; Friedman, Eitan; Banerjee, Shailesh P


    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction.

  11. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)


    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

  12. Xenon Blocks Neuronal Injury Associated with Decompression. (United States)

    Blatteau, Jean-Eric; David, Hélène N; Vallée, Nicolas; Meckler, Cedric; Demaistre, Sebastien; Lambrechts, Kate; Risso, Jean-Jacques; Abraini, Jacques H


    Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS.

  13. Time-dependent effects of systemic lipopolysaccharide injection on regulators of antioxidant defense Nrf2 and PGC-1alpha in neonatal rat brain.


    Correa, Fernando Gabriel; Ljunggren, Elin; Patil, Jaspal; Wang, Xiaoyang; Hagberg, Henrik; Mallard, Carina; Sandberg, Mats


    Background/Aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral N...

  14. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors


    BorbÉly, S.; Jocsak, Gergely; Moldovan, Kinga; Sedlak, Lucie; Preininger, Eva; Boldizsar, Imre; Toth, Attila; Atlason, Palmi T; Molnar, Elek; Vilagi, Ildiko


    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) t...

  15. Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury (United States)


    Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess

  16. Prevention of Noise Damage to Cochlear Synapses (United States)


    neurotrophic factor CNTF in promoting synapse regeneration. KEYWORDS Anandamide Auditory Brainstem Response Calcium Ion Calcium-Permeable AMPA Receptors...excitotoxic trauma (kainic acid) in vitro? f) Does CNTF promote synapse regeneration in vitro as does NT-3? W81XWH-14-1-0494 Annual Progress Report 29... CNTF ) is expressed in the organ of Corti at high levels, comparable to NT-3. We have also found that CNTF is approximately as effective as NT-3 in

  17. Validation of neuroprotective effect of blackberries digested metabolites in a model of neurodegeneration based on mice neurons primary culture


    Costa, Inês de Sousa


    Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências, 2014 Neurodegenerative diseases represent a large and heterogeneous group of neurological disorders with increasing incidence associated with aging. Oxidative stress and glutamate excitotoxicity are thought to be one of the main contributing factors to neurodegeneration. The ingestion of fruits and vegetables have been associated to a decreased risk of neurodegenerative and cardiac di...

  18. Bench to Bedside: Understanding Symptom Response to Acupuncture Treatment and Designing a Successful Acupuncture Treatment Program (United States)


    in combination, at dose levels approximately equivalent to the exposures that occurred during the Gulf War in a rat-model of GWI, caused the...or sarin nerve gas during deployment in veterans with GWI caused an excitotoxic cascade (through potential glutamatergic, oxidative stress and... Malaria 12 60 DEET 11 SS Sand 18 90 Sarin 9 45 Tent heater 11 SS Depleted uranium (DU) 6 30 jet fuel 14 70 Solvents 10 so Oil fires 18 90 a A total

  19. Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin. (United States)

    Fontes, Joseph D; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V; Belousov, Andrei B


    Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.

  20. Transport domain unlocking sets the uptake rate of an aspartate transporter


    Akyuz, Nurunisa; Elka R. Georgieva; Zhou, Zhou; Stolzenberg, Sebastian; Cuendet, Michel A.; Khelashvili, George; Altman, Roger B.; Daniel S. Terry; Freed, Jack H.; Weinstein, Harel; Boudker, Olga; Blanchard, Scott C.


    Glutamate transporters terminate neurotransmission by clearing synaptically released glutamate from the extracellular space, allowing repeated rounds of signaling and preventing glutamate-mediated excitotoxicity. Crystallographic studies on an archaeal homologue, GltPh, showed that distinct transport domains translocate substrates into the cytoplasm by moving across the membrane within a central trimerization scaffold. Here, we report direct observations of these 'elevator-like' transport dom...

  1. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  2. Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Moldovan, Mihai; Marklund, Stefan L.


    inward currents (PICs) being activated at lower firing frequencies and being more pronounced. Conclusion: We demonstrated that, in vivo, at resting membrane potential, spinal motoneurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence...... of an increased PIC and less spike frequency adaptation which may contribute to excitotoxity of these neurones as the disease progresses....

  3. Proteomic Analysis of the Effect of Acupuncture on the Suppression of Kainic Acid-Induced Neuronal Destruction in Mouse Hippocampus


    Bae, Chang-Hwan; Kim, Dong-Soo; Jun, Ye Lee; Kwon, Sunoh; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae


    Kainic acid (KA) is a neurotoxin that induces epileptic seizures and excitotoxicity in the hippocampus. Acupuncture is frequently used as an alternative therapy for epilepsy, and it has been known to protect hippocampal neurons against KA toxicity. Using proteomic analysis, we investigated protein expression changes in the hippocampus following acupuncture stimulation at HT8. Eight-week-old male C57BL/6 mice (20–25 g) received acupuncture treatment at HT8 acupoint bilaterally once a day for 3...

  4. Effects of the whole-body cryotherapy on a total antioxidative status and activities of some antioxidative enzymes in blood of patients with multiple sclerosis-preliminary study


    Miller, Elżbieta; Mrowicka, Małgorzata; Katarzyna MALINOWSKA; Żołyński, Krystian; Kędziora, Józef


    Objective. There is evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. Neutralization of oxidative stress and excitotoxicity, might represent a therapeutic approach to provide neuroprotection in MS. The purpose of this study was to compare changes in total antioxidative status and activities of chosen antioxidative enzymes, such as : SOD, CAT in erythrocytes of patients with MS befor...

  5. Prevention of Alzheimer's disease pathology by cannabinoids: Neuroprotection mediated by blockade of microglial activation


    Ramírez, Belén G.; Blázquez, Cristina; Gómez del Pulgar, Teresa; Guzmán, Manuel; Ceballos, María L. de


    Alzheimer's disease (AD) is characterized by enhanced β-amyloid peptide (βA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after βA treatment, both in vivo and in vitro. He...

  6. Alzheimer's disease; taking the edge off with cannabinoids?


    Campbell, V A; Gowran, A


    Alzheimer's disease is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmarks of the disease are the deposition of β-amyloid protein and hyperphosphorylation of tau, which evoke neuronal cell death and impair inter-neuronal communication. The disease is also associated with neuroinflammation, excitotoxicity and oxidative stress. In recent years the proclivity of cannabinoids to exert a neuroprotective influence has received substantial interes...

  7. A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

    DEFF Research Database (Denmark)

    Aw, Sherry Shiying; Lim, Isaac Kok Hwee; Tang, Melissa Xue Mei


    Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is kno...... of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment....

  8. The Development of Human Organotypic Retinal Cultures (HORCs) to study Retinal Neurodegeneration


    Niyadurupola, Nuwan; Sidaway, Peter; Osborne, Andrew; David C Broadway; Sanderson, Julie


    Abstract Aims To develop human organotypic retinal cultures (HORCs) to study retinal ganglion cell (RGC) death in response to ischaemic and N-methyl-D-aspartate (NMDA) excitotoxic insults, both known to cause loss of RGCs and proposed as mechanisms involved in glaucomatous retinal neurodegeneration. Methods Human donor eyes were obtained within 24hr post mortem. The retina was isolated and explants cultured using two techniques. THY-1 mRNA (as assessed by real time quantitativ...

  9. A Single High Dose of Methamphetamine Induces Apoptotic and Necrotic Striatal Cell Loss Lasting Up to Three Months in Mice


    Tulloch, Ingrid; Afanador, Lauriaselle; Mexhitaj, Ina; Ghazaryan, Nane; GarzaGongora, Arturo G.; Angulo, Jesus A.


    Methamphetamine (METH) is an addictive agent that poses a public health problem due to its toxic effects on neural tissue. We have shown that METH induces striatal lesions (cell loss) within 24 hours of administration. Because cell proliferation has been found to follow excitotoxic and other types of lesions in adult brain, we tested the hypothesis that cell proliferation would follow METH-induced striatal cell death. To that end, METH (30 mg/kg ip) was injected into adult male mice followed ...

  10. Oxidative stress in Parkinson’s disease


    Nikam, Shashikant; Nikam, Padmaja; Ahaley, S. K.; Sontakke, Ajit V.


    Oxidative stress contributes to the cascade, leading to dopamine cell degeneration in Parkinson’s disease. However, oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation. It is therefore difficult to determine whether oxidative stress leads to or is a consequence of, these events. Oxidative stress was assessed by estimating lipid peroxidation product in the form of thioba...

  11. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease. (United States)

    Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu


    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Neuroprotective effects of curculigoside against NMDA-induced neuronal excitoxicity in vitro. (United States)

    Tian, Zhen; Yu, Wei; Liu, Hong-bao; Zhang, Nan; Li, Xu-bo; Zhao, Ming-gao; Liu, Shui-bing


    Glutamate is an important excitatory neurotransmitter in the central nervous system. Excessive accumulation of glutamate can cause excitotoxicity, which plays a key role in spinal cord injury, traumatic brain injury, stroke, and neurodegenerative diseases. Curculigoside (CCGS) is a major bioactive compound isolated from the rhizome of Curculigo orchioides Gaertn. CCGS has an extensive biological effect and has been used in Traditional Chinese Medicine. However, little is known about the neuroprotective effects of CCGS on glutamate-induced excitotoxicity. This study aims to evaluate the neuroprotective effects of CCGS in cultured cortical neurons. The results indicated that treatment with 1 and 10 μM CCGS evidently prevented N-methyl-d-aspartate (NMDA)-induced neuronal cell loss and reduced the number of apoptotic and necrotic cells in a time- and concentration-dependent manner. The neuroprotective effects of CCGS are related to down regulating the apoptotic protein levels and reducing the production of intracellular reactive oxygen species in cultured cortical neurons. These findings give a new insight into the development of natural anti-excitotoxicity agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Han

    Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

  14. Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats. (United States)

    Zhu, Min-xia; Lu, Chao; Xia, Chun-mei; Qiao, Zhong-wei; Zhu, Da-nian


    Excitotoxicity and cytotoxic edema are the two major factors resulting in neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream signal molecular of N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to control the flux of water. In a previous study, we had reported that pretreatment of simvastatin protected the cerebrum from ischemia and reperfusion injury by decreasing neurological deficit score and infarct area (Zhu et al. PLoS One 7:e51552, 2012). The present study used a middle cerebral artery occlusion (MCAO) model to further explore the pleiotropic effect of simvastatin via CaMK II and AQP4. The results showed that simvastatin reduced degenerated cells and brain edema while decreasing the protein expressions of phosphor-CaMK II and AQP4, and increasing the ratios of Bcl-2/Bax, which was independent of cholesterol-lowering effect. Immunocomplexes formed between the subunit of NMDARs-NR3A and AQP4 were detected for the first time. It was concluded that simvastatin could protect the cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the expressions of phosphor-CaMK II and AQP4, and that the interaction between NR3A and AQP4 might provide the base for AQP4 involving in the signaling pathways mediated by NMDARs.

  15. Assessment of therapeutic potential of amantadine in methamphetamine induced neurotoxicity. (United States)

    Thrash-Williams, Bessy; Ahuja, Manuj; Karuppagounder, Senthilkumar S; Uthayathas, Subramaniam; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan


    Methamphetamine epidemic has a broad impact on world's health care system. Its abusive potential and neurotoxic effects remain a challenge for the anti-addiction therapies. In addition to oxidative stress, mitochondrial dysfunction and apoptosis, excitotoxicity is also involved in methamphetamine induced neurotoxicity. The N-methyl-D-aspartate (NMDA) type of glutamate receptor is thought to be one of the predominant mediators of excitotoxicity. There is growing evidence that NMDA receptor antagonists could be one of the therapeutic options to manage excitotoxicity. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was found to possess NMDA antagonistic properties and has shown to release dopamine from the nerve terminals. The current study aimed to evaluate the effect of amantadine pre-treatment against methamphetamine induced neurotoxicity. Results showed that methamphetamine treatment had depleted striatal dopamine, generated of reactive oxygen species and decreased activity of complex I in the mitochondria. Interestingly, amantadine, at high dose (10 mg/kg), did not prevent dopamine depletion moreover it exacerbated the behavioral manifestations of methamphetamine toxicity such as akinesia and catalepsy. Only lower dose of amantadine (1 mg/kg) produced significant scavenging of the reactive oxygen species induced by methamphetamine. Overall results from the present study suggest that amantadine should not be used concomitantly with methamphetamine as it may results in excessive neurotoxicity.

  16. Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration (United States)

    Genius, Just; Geiger, Johanna; Bender, Andreas; Möller, Hans-Jürgen; Klopstock, Thomas; Rujescu, Dan


    Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity. PMID:22347384

  17. Exploring neuroprotective potential of Withania somnifera phytochemicals by inhibition of GluN2B-containing NMDA receptors: An in silico study. (United States)

    Kumar, Gaurav; Patnaik, Ranjana


    N-methyl-d-aspartate receptors (NMDARs) mediated excitotoxicity has been implicated in multi-neurodegenerative diseases. Due to lack of efficacy and adverse effects of NMDA receptor antagonists, search for herbal remedies that may act as therapeutic agents is an active area of research to combat these diseases. Withania somnifera (WS) is being used for centuries as a nerve tonic and Nootropic agents. The present study targets the in silico evaluation of the neuroprotective efficacy of W. somnifera phytochemicals by inhibition of NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B containing NMDARs. We predict Blood Brain Barrier (BBB) penetration, mutagenicity, drug-likeness and Human Intestinal Absorption properties of 25 WS phytochemicals. Further, molecular docking was performed to know whether these phytochemicals inhibit the GluN2B containing NMDARs or not. The results suggest that Anaferine, Beta-Sitosterol, Withaferin A, Withanolide A, Withanolide B and Withanolide D inhibit GluN2B containing NMDARs through allosteric mode similar to the well-known selective antagonist Ifenprodil. These phytochemicals have potential as an essentially useful oral drug to counter NMDARs mediated excitotoxicity and to treat multi-neurodegenerative diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 3-Hydroxykynurenine and quinolinate: pathogenic synergism in early grade Huntington's disease? (United States)

    Guidetti, Paolo; Schwarcz, Robert


    Huntington's Disease (HD), an inherited neurodegenerative disorder, is caused by an abnormal polyglutamine extension of a protein named huntingtin. This genetic defect is believed to result in heightened neuronal susceptibility to excitotoxic injury, a likely mechanism of neurodegeneration in HD. Two neuroactive kynurenine pathway metabolites, quinolinate (QUIN) and kynurenate (KYNA), have been proposed to play critical roles in the precipitation and prevention, respectively, of excitotoxic neuron death in HD. We now provide evidence that a third kynurenine pathway metabolite, 3-hydroxykynurenine (3-HK), should also be considered a pathogen in HD. The brain levels of this free radical generator are increased 5-10-fold in early stage (Grade 1) HD patients. In the same brains, QUIN levels are also significantly elevated in the cortex and in the neostriatum, but not in the cerebellum. In contrast, brain 3-HK and QUIN levels are either unchanged or reduced in Grade 2 and end stage (Grade 3-4) HD patients. Brain KYNA levels are moderately increased during the early disease stages and decrease as the illness progresses. In rats, 3-HK potentiates striatal QUIN toxicity, and this pro-excitotoxic effect can be prevented by free radical scavengers. Taken together, these studies provide further evidence for an involvement of kynurenine pathway metabolites in the early phases of HD neuropathology and suggest novel therapeutic strategies for the disease.

  19. Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase (United States)

    Choi, Yun-Sik; Lin, Stanley L.; Lee, Boyoung; Kurup, Pradeep; Cho, Hee-Yeon; Naegele, Janice R.; Lombroso, Paul J.; Obrietan, Karl


    Excitotoxic cell death is one of the precipitating events in the development of temporal lobe epilepsy. Of particular prominence is the loss of GABAergic hilar neurons. Although the molecular mechanisms responsible for the selective vulnerability of these cells are not well understood, activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway has been implicated in neuroprotective responses to excitotoxicity in other neuronal populations. Here, we report that high levels of the striatal-enriched protein tyrosine phosphatase (STEP), a key regulator of ERK/MAPK signaling, are found in vulnerable somatostatin-immunoreactive hilar interneurons. Under both control conditions and after pilocarpine-induced status epilepticus (SE), ERK/MAPK activation was repressed in STEP-immunoreactive hilar neurons. This contrasts with robust SE-induced ERK/MAPK activation in the granule cell layer of the dentate gyrus, a cell region that does not express STEP. During pilocarpine-induced SE, in vivo disruption of STEP activity allowed activation of the MAPK pathway, leading to immediate-early gene expression and significant rescue from cell death. Thus, STEP increases the sensitivity of neurons to SE-induced excitotoxicity by specifically blocking a latent neuroprotective response initiated by the MAPK pathway. These findings identify a key set of signaling events that render somatostatinergic hilar interneurons vulnerable to SE-induced cell death. PMID:17360923

  20. A distributed-parameter model of the myelinated nerve fiber. (United States)

    Halter, J A; Clark, J W


    This paper presents a new model for the characterization of electrical activity in the nodal, paranodal and internodal regions of isolated amphibian and mammalian myelinated nerve fibers. It differs from previous models in the following ways: (1) in its ability to incorporate detailed anatomical and electrophysiological data; (2) in its approach to the myelinated nerve fiber as a multi-axial cable; and (3) in the numerical algorithm used to obtain distributed model equation solutions for potential and current. The morphometric properties are taken from detailed electron microscopic anatomical studies (Berthold & Rydmark, 1983a, Experientia 39, 964-976). The internodal axolemma is characterized as an excitable membrane and model-generated nodal and internodal membrane action potentials are presented. A system of describing equations for the equivalent network model is derived, based on the application of Kirchoff's Current Law, which take the form of multiple cross-coupled parabolic partial differential equations. An implicit numerical integration method is developed and the numerical solution implemented on a parallel processor. Non-uniform spatial step sizes are used, enabling detailed representation of the nodal region while minimizing the number of total segments necessary to represent the overall fiber. Conduction velocities of 20.2 m sec-1 at 20 degrees C for a 15 microns diameter amphibian fiber and 57.6 m sec-1 at 37 degrees C for a 17.5 microns diameter mammalian fiber are achieved, which agrees qualitatively with published experimental data at similar temperatures (Huxley & Stämpfli, 1949, J. Physiol., Lond. 108, 315-339; Rasminsky, 1973, Arch, Neurol. 28, 287-292). The simulation results demonstrate the ability of this model to produce detailed representations of the transaxonal, transmyelin and transfiber potentials and currents, as well as the longitudinal extra-axonal, periaxonal and intra-axonal currents. Also indicated is the potential contribution

  1. Stimulation-induced Ca(2+) influx at nodes of Ranvier in mouse peripheral motor axons. (United States)

    Zhang, Zhongsheng; David, Gavriel


    In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2+) influx was thought to occur only in pathological conditions such as ischaemia. Using Ca(2+) imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [C(2+)] around nodes of Ranvier. These stimulation-induced [Ca(2+)] elevations require Ca(2+) influx, and are partially reduced by blocking T-type Ca(2+) channels (e.g. mibefradil) and by blocking the Na(+)/Ca(2+) exchanger (NCX), suggesting an important contribution of Ca(2+) influx via reverse-mode NCX activity. Acute disruption of paranodal myelin dramatically increases stimulation-induced [Ca(2+)] elevations around nodes by allowing activation of sub-myelin L-type (nimodipine-sensitive) Ca(2+) channels. The Ca(2+) that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca(2+) influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases. Activity-dependent Ca(2+) signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+)] indicator revealed that during repetitive action potential stimulation, [Ca(2+)] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+)] elevations (∼ 0.1 μm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+)/Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+)] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These

  2. A Study of Preventing Email (Spear) Phishing by Enabling Human Intelligence

    NARCIS (Netherlands)

    M.S. Bargh; A. Padmos; R. Choenni; F. Jansen; N. Stembert


    Cyber criminals use phishing emails in high-volume and spear phishing emails in low volume to achieve their malicious objectives. Hereby they inflict financial, reputational, and emotional damages on individuals and organizations. These (spear) phishing attacks get steadily more sophisticated as

  3. 25 CFR 11.900 - Definitions. (United States)


    ... emotional injury, inflicted by other than accidental means, which causes or creates a substantial risk of death, disfigurement, impairment of bodily functions or emotional health; (4) Has not been provided with adequate food, clothing, shelter, medical care, education or supervision by his or her parent, guardian or...

  4. Exploring the Link between Corporal Punishment and Children's Cruelty to Animals. (United States)

    Flynn, Clifton P.


    Study of college undergraduates (N=267) examined the relationship between corporal punishment inflicted by parents and perpetration of animal abuse. Analyses showed that the association between fathers' corporal punishment and sons' childhood animal cruelty persisted after controlling for child abuse, father-to-mother violence, and father's…

  5. Sympathy and misery in families with drinking problems

    DEFF Research Database (Denmark)

    Järvinen, Margaretha; Bloch, Charlotte


    the sympathy, showing gratitude and/or acknowledging their problems and trying to solve them. Third, the interviewees’ sympathygiving is related to the moral status they ascribe to problem drinkers, and especially their conceptions of alcohol problems as being self-inflicted or caused by circumstances...

  6. First report of clinical presentation of a bite by a running spider ...

    African Journals Online (AJOL)

    This article describes the clinical progression of symptoms over a period of 5 days of a bite inflicted by a Philodromus sp. spider. Commonly known as 'running spiders', these are not considered to be harmful to humans. This report, however, is the first description of an actual bite by a member of this group of spiders ...

  7. Oceanography for Divers: Hazardous Marine Life. Diver Education Series. (United States)

    Somers, Lee H.

    Most people find that the life of the marine environment is beautiful and fascinating. Of the thousands of marine animals and plants, relatively few constitute a real hazard to the diver. Although some species are dangerous and may, in some instances, inflict serious wounds, with a few exceptions marine animals are not aggressive. Most…

  8. Biochemical factors associated with cassava resistance to whitefly

    African Journals Online (AJOL)



    Aug 17, 2017 ... Cassava (Manihot esculenta Crantz) an important food security crop, is inflicted by whitefly (Bemisia tabaci) worldwide, causing direct damage of up to 80% of yield loss. Although resistance to the pest has been associated with antibiosis, changes that occur in metabolite activity, and their effect on the pest ...

  9. Identification of volatile potato sesquiterpenoids and their olfactory detection by the two-spotted stinkbug Perillus bioculatus

    NARCIS (Netherlands)

    Weissbecker, B.; Loon, van J.J.A.; Posthumus, M.A.; Bouwmeester, H.J.; Dicke, M.


    The predaceous stinkbug Perillus bioculatus is attracted towards volatiles emitted by damaged potato plants. Whereas mechanically damaged plants lost attractiveness 1 h after damage was inflicted, attraction was long-lasting when the plants were damaged by Colorado potato beetles Leptinotarsa

  10. Thrips management program for ornamental plants (United States)

    Among the 5,500 (or more) well-described species of thrips (Thysanoptera: Thripidae) worldwide, nearly 1% are known as economically important pests Owing to their polyphagous nature and damage potential to nursery and greenhouse production, thrips inflict millions of dollars loss annually. Thrips ca...

  11. Behavioral responses of the invasive Halyomorpha halys (Stal) to traps baited with stereoisomeric mixtures of 10,11-Epoxy-1-bisabolen-3-OL (United States)

    The brown marmorated stink bug, Halyomorpha halys, is an invasive insect in the United States that is capable of inflicting significant yield losses for fruit, vegetable, and soybean growers. Recently, a male-produced aggregation pheromone of H. halys was identified as a 3.5:1 mixture of (3S,6S,7R,...

  12. Puccinia coronata f. sp. avenae: a threat to global oat production (United States)

    Puccinia coronata f. sp. avenae causes crown rust disease in cultivated and wild oat. The significant yield losses inflicted by this pathogen makes crown rust the most devastating disease in the oat industry. P. coronata f. sp. avenae is a basidiomycete fungus with an obligate biotrophic lifestyle a...

  13. Naval War College Review. Volume 63, Number 4, Autumn 2010 (United States)


    this prosperity: The greater interdependence of economies resulting from globalisation means that great harm can be inflicted upon the economy and...licensing” for limited time spans, “specific operating licensing” for the export of particular services, and “ export authorization” that takes into ac

  14. Intentional injuries and patient survival of burns: a 10-year retrospective cohort in southern Brazil. (United States)

    Duarte, Daniele Walter; Neumann, Cristina Rolim; Weber, Elisabete Seganfredo


    Patients burned intentionally experience extensive injuries with high rates of morbidity and mortality. Nonetheless, there is no consensus if these patients have worse outcomes than unintentional burns considering injury severity and other preexistent comorbidities. We conducted a ten-year retrospective review on all patients treated at the Burn Unit of Hospital de Pronto Socorro, Porto Alegre, Brazil, between 2003 and 2012. The aim was to compare survival of self-inflicted burns and burns from assaults with unintentional injuries using a Multivariable Cox Regression Analysis. 1734 patients were included in the study, 87.7% non-intentional, 6.6% self-inflicted and 5.8% from aggression. Intentional injuries resulted in more severe injuries and were associated with psychiatric disorders and drug abuse. After controlling for injury severity, previous clinical comorbidities and previous psychiatric disorders, only self-inflicted burns correlated significantly with a higher risk of death (HR=1.59, CI 95% 1.05-2.41, p=0.03). Self-inflicted injuries were independently associated with a higher risk of death. Burns from aggression were not associated with higher mortality in this model. Prevention of these injuries must be priority and treating the main associated factors such as drug abuse and psychiatric disorders may lower its occurrence. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  15. Total anti-oxidant status and C-reactive protein values in Nigerians ...

    African Journals Online (AJOL)

    Rev Olaleye

    result in the production of large amounts of free radicals which are harmful to the human body. Antioxidants on the other hand are substances that when present even in low concentrations avidly react with and annihilate free radicals before oxidative damage is inflicted on vital components of the cells. This case-control ...

  16. Spatial multi-criteria decision analysis for modelling suitable habitats of Ornithodoros soft ticks in the Western Palearctic region (United States)

    Ticks are economically and medically important due to the injuries inflicted through their bite, and their ability to transmit pathogens to humans, livestock, and wildlife. Whereas hard ticks have been intensively studied, little is known about soft ticks, even though they can transmit several patho...

  17. Civil Liability for Failing to Report Child Abuse. (United States)

    Lehto, Neil J.


    The article examines the Landeros decision (which ruled that a doctor who fails to report a child abuse victim can be held liable for subsequent injuries inflicted on the child) and discusses three theories of proving civil liability for the failure to report child abuse victims. Addressed are the following topics: the problem of child abuse and…

  18. Transcriptomic analysis of the Olea europaea L. roots during the Verticillium dahliae early infection process

    DEFF Research Database (Denmark)

    Jiménez-Ruiz, Jaime; Pérez, Maria De la O Leyva; Schilirò, Elisabetta


    Olive cultivation is affected by a wide range of biotic constraints. Verticillium wilt of olive is one of the most devastating diseases affecting this woody crop, inflicting major economic losses in many areas, particularly within the Mediterranean Basin. Little is known about gene-expression cha...


    African Journals Online (AJOL)


    Mar 1, 2013 ... The results obtained can be useful to food process engineers in designing fruits packages to reduce ... mestic and inter-state transportation Berardinelli et .... materials. This is because these materials are gener- ally rougher and harder than the others. Foam mate- rials inflicted trace damage to the apple ...

  20. "Broken-Off Like Limbs from a Tree": Fractured Identity in Caryl Phillips's "Crossing the River (1993)" (United States)

    Labidi, Abid Larbi


    My major purpose in studying Caryl Phillips's widely acclaimed novel "Crossing the River" is to examine, through a close textual analysis, the severe identity crisis inflicted upon slaves under the three-century long slavery institution. I explore how slaves' tragic rift of separation from their African homelands led to a disastrous loss…

  1. The nature of culture: technological variation in chimpanzee predation on army ants revisited

    DEFF Research Database (Denmark)

    Schöning, Caspar; Humle, Tatyana; Möbius, Yasmin


    ; species foraging in leaf-litter with less aggressive workers that inflict less painful bites are harvested with short tools and by the "direct-mouthing" technique. However, prey species characteristics do not explain several differences in army-ant-eating between Bossou (Guinea) and Taï (Ivory Coast...

  2. Women's Political Representation & Participation in Decentralized ...

    International Development Research Centre (IDRC) Digital Library (Canada)


    2008, inflicted women's rights since it accused women become sexual material and will be sanctioned because arousing lust and desire of men. • The ongoing debate to suspend the Draft Law on Health for about 14 years, particularly on the regulation of safe abortion. Yet, there are. 2.3 million unsafe abortion per year in.

  3. Ecology, life history and management of tropilaelaps mites (United States)

    Parasitic mites are the major threat of the Western honey bee, Apis mellifera. For much of the world, Varroa destructor single-handedly inflicts unsurmountable problems to A. mellifera beekeeping. However, A. mellifera in Asia is also faced with another genus of destructive parasitic mite, Tropilae...

  4. Nuclear Power for Catalonia: The Role of the Official Chamber of Industry of Barcelona, 1953-1962 (United States)

    Salom, Francesc X. Barca


    Between 1939 and 1959, the regime led by General Franco pursued a policy of economic self-sufficiency. This policy inflicted great injury on Spanish science and industry, not least in Catalonia, and in its capital, Barcelona. In response, Catalan industry looked to a future made more promising by the advent of nuclear power. This paper describes…

  5. Influence of anoxia on the induction of mutations by phenylalanine radicals during gamma-irradiation of plasmid DNA in aqueous solution.

    NARCIS (Netherlands)

    Kuipers, G.K.; Slotman, B.J.; Reitsma-Wijker, CA; Andel, R.J.; Poldervaart, H.A.; Lafleur, M.V.M.


    When DNA is irradiated in aqueous solution, most of the damage is inflicted by water-derived radicals. This is called the indirect effect of ionizing radiation. However in whole cells not only the primary formed water radicals play a role, because some cellular compounds form secondary radicals

  6. Energy cost of balance control during walking decreases with external stabilizer stiffness independent of walking speed

    NARCIS (Netherlands)

    Ijmker, T.; Houdijk, J.H.P.; Lamoth, C.J.C.; Beek, P.J.; van der Woude, L.H.V.


    Human walking requires active neuromuscular control to ensure stability in the lateral direction, which inflicts a certain metabolic load. The magnitude of this metabolic load has previously been investigated by means of passive external lateral stabilization via spring-like cords. In the present

  7. Fetal and infant origins of childhood eczema, allergic sensitization and allergy

    NARCIS (Netherlands)

    N.J. Elbert (Niels)


    markdownabstractEczema is a common chronic inflammatory skin disease in childhood that inflicts a substantial physical, psychosocial and economic burden. Eczema may occur solely or coincide with allergic sensitization and symptoms of allergy as part of an atopic constitution. Because the

  8. Associations between School Connection and Depressive Symptoms from Adolescence through Adulthood: The Moderating Influence of Early Adversity (United States)

    Markowitz, Anna J.


    Depression is the most common psychiatric disorder worldwide. Conservative estimates Suggest that 20% of Americans will experience depression during their lifetime, inflicting high interpersonal, labor market, and health care costs. Although depression is highly heritable, environmental factors can powerfully influence its development both…

  9. Tri-trophic interactions affect density dependence of seed fate in a tropical forest palm

    NARCIS (Netherlands)

    Visser, M.D.; Muller-Landau, H.C.; Wright, J.; Rutten, G.; Jansen, P.A.


    Natural enemies, especially host-specific enemies, are hypothesised to facilitate the coexistence of plant species by disproportionately inflicting more damage at increasing host abundance. However, few studies have assessed such Janzen–Connell mechanisms on a scale relevant for coexistence and no

  10. Tri-trophic interactions affect density dependence of seed fate in a tropical forest palm

    NARCIS (Netherlands)

    Visser, Marco D.; Muller-Landau, Helene C.; Wright, S. Joseph; Rutten, Gemma; Jansen, Patrick A.


    Natural enemies, especially host-specific enemies, are hypothesised to facilitate the coexistence of plant species by disproportionately inflicting more damage at increasing host abundance. However, few studies have assessed such Janzen-Connell mechanisms on a scale relevant for coexistence and no

  11. Critical C Course 2

    African Journals Online (AJOL)

    Special investigations which may assist in assessment and treatment include: pH and electrolytes, acid-base balance, arterial blood gasses and an ECG where applicable. Further reading available at In a Nutshell. • Most local scorpions are relatively harmless, and although they can inflict quite a painful.

  12. Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Rook, M; Lely, AT; Kramer, AB; van Goor, H; Navis, G

    Background. In man, differences in angiotensin converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we

  13. Recurrent Bartholin's gland abscess in pregnancy: An uncommon ...

    African Journals Online (AJOL)

    including chorioamnionitis, sternoclavicular septic arthritis and septicaemia, none of which developed in this patient.[8,9]. There is no documented evidence of the effects of Bartholin's abscess on pregnancy and vice‑versa. However, septicaemia is a well‑known complication of abscesses, which has the potential of inflicting ...

  14. The Noncommissioned Officer and Petty Officer: Backbone of the Armed Forces (United States)


    be Free and Independent States; that they are Absolved from all Allegiance to the British Crown , and that all political connection between them and...shall not be required, nor excessive fines imposed, nor cruel and unusual punishments inflicted. Amendment IX The enumeration in the Constitution, of

  15. accidental injuries in children (physical child abuse)

    African Journals Online (AJOL)


    Dec 6, 2016 ... Abstract: Background: Bruises commonly occur in children and are often due to minor accidental injuries. However, they can also occur in bleeding disorders or inflicted injuries (physical abuse) and is often the most common visible manifestation of child physical abuse. Objective: This paper aims at.

  16. Locust Control by early identification of breeding sites

    NARCIS (Netherlands)

    Huis, van A.


    Locust outbreaks occur when conditions for breeding become favorable. As a reaction to an increase in density, locusts change their behavior from solitarious to gregarious. When fully gregarious, they are capable of migrating in swarms to agricultural areas, where they can inflict considerable

  17. Euripides' Medea: a psychodynamic model of severe divorce pathology. (United States)

    Jacobs, J W


    Analysis of Euripides' play, Medea, and a divorcing family suggests that divorce between a narcissistically scarred, embittered, dependent woman and a pathologically narcissistic, devaluing man may lead to the mother's attempt to sever father-child contact as a means of revenging the injury inflicted on her by the loss of a selfobject, her hero-husband.

  18. Antinociceptive effect of Pleurotus ostreatus (Oyster Mushroom ...

    African Journals Online (AJOL)

    Hot water at 550C was used to determine the nociceptive responses of the animals to detect anti-nociceptive effects of Pleurotus ostreatus extracts as compared to the control in hot water inflicted pain. The results suggested that Pleurotus ostreatus aqueous extract exhibits antinociceptive properties against thermal stimulus ...

  19. Management of common animal bites in the emergency centre

    African Journals Online (AJOL)

    In South Africa there are a variety of animals that have the potential to inflict injuries. However, such injuries are relatively rare compared with dog bites, which are by far the most frequently encountered animal bites managed in our emergency centres. Many of the principles in the management of dog bites also apply to bites ...

  20. Vatwa Resettlement Sites

    International Development Research Centre (IDRC) Digital Library (Canada)

    examining structural or indirect violence (material deprivation, inequality, exclusion), direct violence (direct infliction of physical or psychological harm), overt conflict and its links to violence and different types of crime. We note that not all types of violence are considered as crime (for example, violence by the state), and not ...

  1. The multiple faces of calcineurin signaling in Caenorhabditis ...

    Indian Academy of Sciences (India)

    Analyses of cna-1/tax-6 and cnb-1 interacting proteins and regulators of the phosphatase in this fascinating worm model have an immense scope to identify potential drug targets in various parasitic nematodes, which cause many diseases inflicting huge economic loss; and also for many human diseases, particularly ...

  2. The Effects of War on Children: School Psychologists' Role and Function (United States)

    Lasser, Jon; Adams, Krysta


    War may be the most profound psychosocial stressor on child and adolescent development, for it has the potential to inflict loss, disruption of stability, deleterious health effects and family/community system disorganization. This article reviews the literature regarding the effects of war on children and explores the role and function of the…

  3. Changing therapeutic geographies of the Iraqi and Syrian wars

    NARCIS (Netherlands)

    Dewachi, O.; Skelton, M.; Nguyen, V.K.; Fouad, F.M.; Ghassan, A.S.; Maasri, Z.; Giacaman, R.


    The health consequences of the ongoing US-led war on terror and civil armed conflicts in the Arab world are much more than the collateral damage inflicted on civilians, infrastructure, environment, and health systems. Protracted war and armed conflicts have displaced populations and led to lasting

  4. Recession Amnesia: Prospects for New England Higher Education (United States)

    Halfond, Jay A.


    Universities are organized to assume uninterrupted growth in enrollments and endowments, steady public funding, an annual ability to inflict tuition hikes on students and their families, everlasting degree programs, vast building operations and permanent commitments to a senior professoriate. Lacking an agile and responsive governance structure,…

  5. Honey improves healing of circumscribed excision injury to the ...

    African Journals Online (AJOL)

    Background: Honey promotes wound healing. Objective: In this study, we described the anatomical perspective of honey on wound healing in male rats. Methods: The twenty-four male rats used were randomly divided equally into treated Experimental (E) and Control (C) groups. Infliction of wound done under anaesthesia; ...

  6. Eavesdropping on coconut rhinoceros beetles, red palm weevils, Asian longhorned beetles, and other invasive travelers (United States)

    As global trade increases, invasive insects inflict increasing economic damage to agriculture and urban landscapes in the United States yearly, despite a sophisticated array of interception methods and quarantine programs designed to exclude their entry. Insects that are hidden inside soil, wood, or...

  7. Retinabloedingen als teken van kindermishandeling

    NARCIS (Netherlands)

    van den Hoven, C M L; van Berkestijn, F M C|info:eu-repo/dai/nl/30481847X; Russel-Kampschoer, I M B|info:eu-repo/dai/nl/30481444X; Karst, W A; Voskuil-Kerkhof, E S M


    Inflicted traumatic brain injury (ITBI) - a possible result of child abuse - is difficult to diagnose, yet the diagnosis bears great impact on patients and their relatives. The purpose of this paper is to describe ophthalmologic findings that can be seen in relation to ITBI. For exemplification,

  8. New interpretation of arterial stiffening due to cigarette smoking using a structurally motivated constitutive model

    DEFF Research Database (Denmark)

    Enevoldsen, Marie Sand; Henneberg, Kaj-Åge; Jensen, Jørgen Arendt


    Cigarette smoking is the leading self-inflicted risk factor for cardiovascular diseases; it causes arterial stiffening with serious sequelea including atherosclerosis and abdominal aortic aneurysms. This work presents a new interpretation of arterial stiffening caused by smoking based on data...

  9. Cerebral damage caused by nail gun injury

    Directory of Open Access Journals (Sweden)

    Andersen Chris Hedeman


    Full Text Available Background Accidents with nail guns are rather common, especially in the construction industry. Most injuries involve the extremities and several present with intracerebral injuries. When the patient is unconscious, it can be a big challenge to determine whether the injury is an accident, self-inflicted or a criminal act.

  10. An Asian ambrosia beetle Euwallacea fornicatus and its novel symbiotic fungus Fusarium sp. pose a serious threat to the Israeli avocado industry (United States)

    The ambrosia beetle Euwallacea fornicatus Einchoff was first recorded in Israel in 2009. A novel unnamed symbiotic species within Clade 3 of the Fusarium solani species complex, carried in the mandibular mycangia of the beetle, is responsible for the typical wilt symptoms inflicted on avocado (Perse...

  11. Protein Dynamics in Mammalian Genome Maintenance

    NARCIS (Netherlands)

    A. Zotter (Angelika)


    textabstractThe integrity of the genome, carrier of the blueprint for each organism, is under constant attack from environmental as well as endogenous DNA damaging agents. An agent with substantial impact on our DNA is the UV-fraction of sunlight. It inflicts bulky DNA lesions, which can interfere

  12. Perimeter Security and Intruder Detection Using Gravity Gradiometry: A Feasibility Study (United States)


    get close enough to their targets to inflict harm. A truck containing the equivalent of 10 tons of TNT explosive was detonated less than 100 feet...time observed quantity results in vastly different FAR values. In hopes of decreasing the apparent FAR, some PIDS distributors recategorize false

  13. The Art Association/Higher Education Partnership: Implementing Residential Professional Development (United States)

    Charland, William


    In-service professional development in education began informally in the early nineteenth-century as a means of disseminating classroom management techniques, specifically addressing ways in which corporal punishment could be delivered to a child without inflicting serious injury. This initial effort paralleled a concern regarding children's…

  14. Antinociceptive effect of Pleurotus ostreatus (Oyster Mushroom ...

    African Journals Online (AJOL)


    aqueous extracts and group five treated with 15 mg/kg Aspirin (a standard drug) as positive control. Hot water at 550C was used to determine the nociceptive responses of the animals to detect anti-nociceptive effects of Pleurotus ostreatus extracts as compared to the control in hot water inflicted pain. The results suggested ...

  15. Nigerian Veterinary Journal 2003290): 63 - 67

    African Journals Online (AJOL)

    sadistic reasons as cruelty, whereas the other school of thought included suffering inflicted for reasons such as, fur production, meat and animal testing or vivisection (Munro, 1999). Jurisdictions around the world have enacted statute prohibiting cruelty to animals. These statutes provide minimal care of animals, but do not ...

  16. Sustainable Development at Risk

    International Development Research Centre (IDRC) Digital Library (Canada)

    The book addresses the miseries inflicted by egocentric ideologies that are claimed to be divinely dictated and imposed on others by force. It illustrates the advantages of south-south cooperation between and among nations at different stages of economic and technological development, as opposed to the tied aid policies ...

  17. Discipline or Punish? Some Suggestions for School Policy and Teacher Practice (United States)

    Yang, K. Wayne


    This article seeks to restore a counter-narrative of discipline as distinct from punishment. Punishment is retribution for an offense, an exclusionary act by which students are removed from the opportunity to learn. It is harm inflicted by an external agent as a mechanism through which outside regulation becomes internalized subjectivity. Too…

  18. An Economic Model of Workplace Mobbing in Academe (United States)

    Faria, Joao Ricardo; Mixon, Franklin G., Jr.; Salter, Sean P.


    Workplace bullying or mobbing can be defined as the infliction of various forms of abuse (e.g., verbal, emotional, psychological) against a colleague or subordinate by one or more other members of a workplace. Even in the presence of academic tenure, workplace mobbing remains a prevalent issue in academe. This study develops an economic model that…

  19. Post-laparotomy haemoptysis due to broncho-abdominal fistula ...

    African Journals Online (AJOL)

    as a right-sided lung abscess.6 Broncho-abdominal fistula (BAF) is similarly rare with a search yielding two reports .... conservative treatment without needing surgery.7. The use of sampling tracers such as Xenon-133 ... fundus was thought to be a result of the damage inflicted by the swab abscess complex in the left upper ...

  20. The pattern of sharps injury to health care workers at Witbank Hospital

    African Journals Online (AJOL)

    Results: A total of 435 HCWs completed the questionnaire. 1. A total of 46.7% of respondents had suffered from either needlestick/sharps injury (74.47%) or contamination of skin/mucous membranes. (25.53%). 2. A total of 76.9% of all needlestick/sharps injuries were inflicted by injection needles. 3. Taking blood was the ...

  1. Lithuanian Freedom Fighters’ Tactics Resisting the Soviet Occupation 1944-1953 (United States)


    Soviets. The mobile defense operation lasted for about five hours, inflicting 67 KIAs on the Soviet side while on the LFF side only six fighters...advantage of operating as motorized units. The LFF could easily identify the Soviet units’ avenues of approach and adapt a scheme of maneuver accordingly to

  2. Paternal Alcoholism: Consequences for Female Children (United States)

    Dehn, Julia


    The consequences of substance abuse and addiction are profound and depredating. The desolation is incalculable in estimating the psychological damage and trauma inflicted on the children of addicted parents. According to studies and statistics gathered by the National Association for Children of Alcoholics, "there are more than 20 million children…

  3. An atypical cause of alkali chemical burn: a case report. (United States)

    Boutefnouchet, T; Moiemen, N; Papini, R


    It has already been reported that wet ash turns into a strong alkali agent, which can cause full-thickness skin burns. A case is presented which has the particularity of sustained, self-inflicted contact with wet ash. The coal used was the self-igniting type normally used for burning scented weed or for smoking the hubbly bubbly or shisha pipe.

  4. An Atypical Cause of Alkali Chemical Burn: a Case Report


    Boutefnouchet, T; Moiemen, N.; Papini, R.


    It has already been reported that wet ash turns into a strong alkali agent, which can cause full-thickness skin burns. A case is presented which has the particularity of sustained, self-inflicted contact with wet ash. The coal used was the self-igniting type normally used for burning scented weed or for smoking the hubbly bubbly or shisha pipe.

  5. Does Wolbachia infection affect Trichogramma atopovirilia behaviour?

    NARCIS (Netherlands)

    Almeida, de R.P.; Lenteren, van J.C.; Stouthamer, R.


    Unisexual Trichogramma forms have attracted much attention due to their potential advantages as biocontrol agents. Fitness studies have been performed and understanding the cost that Wolbachia may inflict on their hosts will help in deciding if Wolbachia infected (unisexual) forms are indeed better

  6. Towards a "Common" View of Difficult Past? The Representation of Atomic Bombings of Hiroshima and Nagasaki in Trilateral Teaching Materials (United States)

    Szczepanska, Kamila


    The centrality of atomic bombings of Hiroshima and Nagasaki in Japanese collective memory has been often perceived by the country's neighbours, i.e. the People's Republic of China and South Korea, as a pillar of the country's (alleged) "victim consciousness" and amnesia in regard to the suffering inflicted on others. For this reason, the…

  7. Livestock Husbandry and Snow Leopard Conservation

    NARCIS (Netherlands)

    Mohammad, Ghulam; Mostafawi, Sayed Naqibullah; Dadul, Jigmet; Rosen, Tatjana; Mishra, Charudutt; Bhatnagar, Yash Veer; Trivedi, Pranav; Timbadia, Radhika; Bijoor, Ajay; Murali, Ranjini; Sonam, Karma; Thinley, Tanzin; Namgail, Tsewang; Prins, Herbert H.T.; Nawaz, Muhammad Ali; Ud Din, Jaffar; Buzdar, Hafeez


    Livestock depredation is a key source of snow leopard mortality across much of the species' range. Snow leopards break into livestock corrals, killing many domestic animals and thereby inflicting substantial economic damage. Locals may retaliate by killing the cat and selling its parts.

  8. Feeding, growth and metabolism of the marine heterotrophic dinoflagellate Gyrodinium dominans

    DEFF Research Database (Denmark)

    Schmoker, Claire; Thor, Peter; Hernández-león, Santiago


    may inflict high metabolic costs. Gross growth efficiencies (GGEs), determined for G. dominans in both food availability conditions, were within the range of values reported for other heterotrophic protozoans, and while GGE decreased when concentrations of food were high in organisms fed a single...

  9. A skin-picking disorder case report: a psychopathological explanation

    Directory of Open Access Journals (Sweden)

    Ângela Ribeiro


    Full Text Available We describe the case of a 44-year-old woman, without known previous psychiatric history, hospitalized after a significant hemorrhage caused by self-inflicted deep facial dermal lesions (with muscle exposition. Psychopathological possible explanations of this case, as in similar reviewed ones, are related to frustration, aggression, and impulsivity.

  10. The Leaderless Social Movement Organization: Unstoppable Power or Last-Ditch Effort (United States)


    achieving those goals. The ELF’s goals are to “educate,” “inflict economic damage,” and “avoid harming any life.” These goals, digested in context of the... maize .”207 Other targets in recent years have included fast food “restaurants (including McDonald’s and Kentucky Fried Chicken), meat shops, pet

  11. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Objective: During the wound healing process, lymphatic regeneration in the injured skin has not been fully investigated. This work was designed to study the regeneration of lymphatic vessels in rat incisional wounds in relation to the duration after the wound infliction. Material and methods: We studied the regeneration of ...

  12. (Tomato) Accelerate or Retard Wound Healing in Wistar Rats?

    African Journals Online (AJOL)

    The study aimed at determining the effects of Lycoperscon esculentum on the wound healing processes of wistar rats. Excisional wounds were inflicted on the upper dorsolateral trunk of 20 adult male wistar rats. The wounds were dressed every three days (experimental with methanol extract of Lycoperscon esculentum and ...

  13. Variations in Wounding by Relationship Intimacy in Homicide Cases (United States)

    Trojan, Carrie; Krull, Amy C.


    There are numerous examples in the homicide literature of a presumed connection between the victim-offender relationship and the manner, extent, and body location of wounds inflicted in homicides. The current study examined variations in wounding patterns according to the intimacy of the victim-offender relationship in a sample of urban homicides…

  14. Initial administration of hydroxyethyl starch vs lactated Ringer after liver trauma in the pig

    DEFF Research Database (Denmark)

    Zaar, M.; Lauritzen, B.; Secher, Niels H.


    BACKGROUND: This study tested the circulatory effectiveness of post-trauma administration of a large intravascular volume expander, hydroxyethyl starch 130/0.4 (HES), vs standard lactated Ringer's solution (RL). METHODS: Liver injury was inflicted in 14 pigs [31 (4) kg; mean (sd)] and treatment...

  15. Skeletal imaging of child abuse (non-accidental injury)

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, Amaka [Great Ormond Street Hospital, Radiology Department, London (United Kingdom); Rijn, Rick R. van [Academic Medical Centre Amsterdam, Department of Radiology, Amsterdam Zuid-Oost (Netherlands); Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K. [Children' s Hospital Boston, Radiology Department, Boston, MA (United States)


    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse. (orig.)

  16. When Teens Turn Cyberbullies (United States)

    Strom, Paris S.; Strom, Robert D.


    Cyber harassment involves using an electronic medium to threaten or harm others. E-mail, chat rooms, cell phones, instant messaging, pagers, text messaging, and online voting booths are tools used to inflict humiliation, fear, and a sense of helplessness. This type of intimidation differs from traditional bullying in several important ways. Unlike…

  17. Strategies to Prevent and Heal the Mental Anguish Caused by Cyberbullying (United States)

    Froeschle, Janet G.; Mayorga, Mary; Castillo, Yvette; Hargrave, Terry


    Few middle school educators have escaped the numerous warnings regarding face-to-face school bullying. While this threat is certainly real, the more common danger inflicted via technology, cyberbullying, is relatively unknown to teachers and parents. Cyberbullying has moved bullying behaviors from the schoolyard to a worldwide audience. This…

  18. The pattern of infections among under-fives: a call for actions

    African Journals Online (AJOL)

    instance, the pain inflicted by consequences of infectious ailments is quite extreme (death, disabilities ... MeThODs. A cross-sectional, community based survey was conducted at Makulu ward of Dodoma district (the .... Also in this survey we assessed the pattern of dental caries among the study sample with the results as.

  19. Reposturing the Force: U.S. Overseas Presence in the Twenty-first Century (United States)


    in Greenland, Iceland, the Azores, Acapulco, the Galapagos Islands, and Recife and Fortaleza in Brazil, for example—were provided by a number of...for some time and inflicted numerous casualties. For a gripping account, see Sean Naylor, Not a Good Day to Die (New York: Penguin , 2005). In Operation

  20. Successful penile reimplantation and systematic review of world literature

    Directory of Open Access Journals (Sweden)

    J.E. Mensah


    Conclusion: Self-inflicted penile amputation may manifest as first psychotic break in apparently normal subjects. Though microscopic neurovascular reconstruction is the gold standard, macrosurgical reimplantation of penis by an experienced surgeon in the absence of a microscope yields satisfactory results.

  1. Do differences in inducible resistance explain the population dynamics of birch and pine defoliators? (United States)

    Seppo Neuvonen; Pekka Niemela


    Damage inflicted by insects may trigger responses in their host plants resulting either in immediate effects on herbivores either rapidly or in effects upon subsequent herbivore generations. Differentiation between rapid and delayed inducible resistance is essential since the two responses affect the population dynamics of herbivores in fundamentally different ways (...

  2. Trampling, defoliation and physiological integration affect growth, morphological and mechanical properties of a root-suckering clonal tree

    NARCIS (Netherlands)

    Xu, L.; Yu, F.H.; Drunen, van E.; Schieving, F.; Dong, M.; Anten, N.P.R.


    Background and Aims Grazing is a complex process involving the simultaneous occurrence of both trampling and defoliation. Clonal plants are a common feature of heavily grazed ecosystems where large herbivores inflict the simultaneous pressures of trampling and defoliation on the vegetation. We test

  3. The Role of Microglial Subsets in Regulating Traumatic Brain Injury (United States)


    subset frequencies present in the brain fol- lowing TBI, single-cell suspensions from TBI and sham-injured brain contralateral and circular craniec- tomy. TBI was inflicted by a 2 mm circular, flat pneumatic piston traveling at 3 m/s, penetrating 1.5 mm, for 150 ms (Amscien

  4. Chinua Achebe: A re-assessment

    African Journals Online (AJOL)

    tradition in which the voice of immemorial community, vestiges of primordial ritual and ceremony, and a judicious ..... repeats ad nauseam that “a man must dance the dance prevalent in his lifetime” and that the “world is like a .... of reconstruction, of reinstitution, of healing the many wounds inflicted on us by the long years of ...

  5. Mizan 2.2 post-print

    African Journals Online (AJOL)


    2 No.2, July 2008 doms proclaimed in the Universal Declaration of Human Rights and reaf- firmed and developed in international instruments in this field. (2). (2) Any act of enforced disappearance places the persons subjected thereto out- side the protection of the law and inflicts severe suffering on them and their families.

  6. An Era of Persistent Engagement (United States)


    cause, not just their country of origin . The terror some non-state actors are able to inflict does not take issue with people‘s politics; it...sovereign states. They include organizations such as McDonald‘s, Adidas or Nike, and large hotel chains such as Best Western or Hilton

  7. The Shariah Crisis in Nigeria: An Insider View+1 | ORIOLA | IFE ...

    African Journals Online (AJOL)

    What degree of popularity and acceptability does a law require to achieve its objectives in the context of Nigeria's heterogeneity? What is the relevance of the source and constituents of a law to its acceptability and conformability? How could the re introduction of the Sharia criminal jurisprudence inflict a wound so deep on ...

  8. Potential for biological control of native North American Dendroctonus beetles (Coleoptera: Scolytidae) (United States)

    M.C. Miller; John C. Moser; M. McGregor; J.C. Gregoire; M. Baisier; D.L. Dahlsten; R.A. Werner


    Bark beetles of the genus Dendroctonus inflict serious damage in North American coniferous forests. Biological control, which has never been seriously attempted with bark beetles in the United States, should be reconsidered in light of results disclosed here. Impact of indigenous associates is discussed, as well as previous, unsuccessful attempts to...

  9. Increased size of cotton root system does not impart tolerance to Meloidogyne incognita (United States)

    Plant tolerance or intolerance to parasitic nematodes represent a spectrum describing the degree of damage inflicted by the nematode on the host plant. Tolerance is typically measured in terms of yield suppression. Instances of plant tolerance to nematodes have been documented in some crops, inclu...

  10. 45 CFR Appendix A to Part 73 - List of Some Offenses for Which Disciplinary Action May Be Taken (United States)


    ...-inclusive. The “Code of Ethics for Government Service” is not cited because of its general applicability but.... Engaging in wasteful actions or behavior in the performance of assigned duties; conducting non-Government... refusal to carry out lawful orders or assignments given. 4. Disruptive behavior, such as: a. Inflicting or...

  11. Curriculum as Conversation: Vulnerability, Violence, and Pedagogy in Prison (United States)

    O'Donnell, Aislinn


    It is difficult to respond creatively to humiliation, affliction, degradation, or shame, just as it is difficult to respond creatively to the experience of undergoing or inflicting violence. In this article Aislinn O'Donnell argues that if we are to think about how to address gun violence--including mass shootings- in schools, then we need to talk…

  12. Differentiating Adolescent Self-Injury from Adolescent Depression: Possible Implications for Borderline Personality Development (United States)

    Crowell, Sheila E.; Beauchaine, Theodore P.; Hsiao, Ray C.; Vasilev, Christina A.; Yaptangco, Mona; Linehan, Marsha M.; McCauley, Elizabeth


    Self-inflicted injury (SII) in adolescence marks heightened risk for suicide attempts, completed suicide, and adult psychopathology. Although several studies have revealed elevated rates of depression among adolescents who self injure, no one has compared adolescent self injury with adolescent depression on biological, self-, and informant-report…

  13. Deep Sea Moorings Fishbite Handbook (United States)


    strand, parallel yarns encased in a braided Dacron cover ( Whitehill Manufacturing Co.). -28- "Causes" of damage inflicted to each of these rope types...act as a separation plate, thus preventing the formation of vortex shedding. Ropes equipped with plastic ribbons or protruding "hairs" will also be

  14. Surveillance of Suicidal Behavior January through December 2013 (United States)


    Disorder . i Substance Use Disorder includes Drug or Alcohol Use Disorders . j Personality Disorders include Borderline or Antisocial Personality ...include Borderline or Antisocial Personality Disorders . Public Health Report No. S.0008057-13, January through December 2013 D-27 Figure D-8... Antisocial Personality Disorders . m Based on ICE-9 E-codes for self-inflicted injuries which first appear in medical

  15. Update on bacterial meningitis: epidemiology, trials and genetic association studies

    NARCIS (Netherlands)

    Kasanmoentalib, E. Soemirien; Brouwer, Matthijs C.; van de Beek, Diederik


    Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of

  16. Occupational cow horn eye injuries in Ibadan, Nigeria | Ibrahim ...

    African Journals Online (AJOL)

    This case series aims to describe the clinical features, management, and outcome of occupational eye injuries caused by cow horns and to recommend possible preventive measures. A review of patients with cow horn inflicted eye injuries seen at the University College Hospital, Ibadan between January 2006, and ...

  17. Pediatric constrictive asphyxia a rare form of child abuse: A report of two cases

    NARCIS (Netherlands)

    Vester, M. E. M.; Bilo, R. A. C.; Nijs, H. G. T.; van Rijn, R. R.


    We present two cases of infants who died under suspicious circumstances. After clinical and legal investigations, non-accidental constrictive asphyxia inflicted by one of the parents was established. The first case presents a to date not yet reported, unique mechanism of trauma. In order to stop his

  18. Subsoil compaction of a Vertic Cambisol persists three decades after wheel traffic

    DEFF Research Database (Denmark)

    Lamandé, Mathieu; Schjønning, Per

    activity in Finland. The compaction treatment was inflicted 29 years prior to investigation and included four passes with a tractor-trailer combination with wheel loads up to 4.8 Mg and inflation pressures of 700 kPa. Gas diffusion and air permeability measurements were combined with pycnometer...

  19. Multimodal imaging in handheld laser-induced maculopathy. (United States)

    Bhavsar, Kavita V; Wilson, Deanna; Margolis, Ron; Judson, Peter; Barbazetto, Irene; Freund, K Bailey; Cunningham, Emmett T


    To describe the clinical and imaging findings in 3 patients with maculopathy secondary to handheld laser exposure. Retrospective, observational case series. We evaluated the multimodal imaging including fundus autofluorescence and spectral-domain optical coherence tomography (OCT) for 3 patients with histories of exposure to handheld lasers. An 18-year-old woman with a history of repetitive self-inflicted handheld laser exposure was found to have bilateral outer retinal streaks in the macula and the superior peripheral retina on both ophthalmoscopy and multimodal imaging. Initial spectral-domain OCT revealed vertical hyper-reflective bands at the level of the outer retina corresponding to the streaks. An 11-year-old boy who played with a green laser developed a yellow foveal lesion and outer retinal streaks in the superior macula. Spectral-domain OCT showed vertical hyper-reflective bands in the outer retina corresponding to the streaks. A 14-year-old boy developed bilateral focal foveal lesions and ellipsoid loss on spectral-domain OCT following peer-inflicted laser injury. In a series of 3 patients, outer retinal streaks were associated with self-inflicted handheld laser injury. In contrast, accidental and peer-inflicted laser injuries were found to result in focal foveal lesions. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Once More unto the Breaching Experiment: Reconsidering a Popular Pedagogical Tool (United States)

    Braswell, Matthew


    Instructors frequently utilize breaching experiments in an attempt to "bring sociology to life." However, an uncritical embrace of breaching experiments obscures the complexity of their possible effects on participants and subjects. These experiments have real potential to inflict deleterious consequences on individuals and groups.…