Neuroscience Centre Research Articles

Choroid artery occlusion after treatment of ICA termination aneurysm: was it caused by stent induced vasospasm?

Dear Sirs: Endovascular occlusion has become the main treatment for cerebral aneurysms in the last decade. This development was much facilitated by the ISAT trial [1] for ruptured aneurysms, but coiling, stenting and flow diversion are now also widely used for unruptured cases. While endovascular treatment is usually less invasive than surgical aneurysm clipping, coil occlusion of an aneurysm seems less durable. This has led to the increasing use of stents to reconstruct the vessel wall for the prevention of recurrences. If an elective stent placement is performed under appropriate antiplatelet medication, stentrelated complications such as thrombotic stent occlusion and embolic events are infrequent [2, 3]. We report on a rare complication after placement of a selfexpanding endovascular stent, leading to a disabling stroke in a young patient with an unruptured internal carotid artery (ICA) aneurysm. A 27-year-old female patient, who had delivered a healthy daughter 6 weeks previously, presented to her local hospital with transient left-sided weakness. Vascular risk factors included obesity (BMI=35 kg/m) and smoking. A probable transient ischaemic attack (TIA) was diagnosed, and the patient was investigated accordingly. While no obvious aetiologywas found for the TIA, her brain imaging had shown an incidental lesion, which was suggestive of a left ICA aneurysm with a diameter of around 10 mm. A subsequent CT angiogram (CTA) done at the local neurosciences centre confirmed the presence of a broad-based left ICA termination aneurysm with a maximum diameter of 12 mm, mostly extending on to the left M1 segment, but also slightly affecting the A1. No other aneurysm was seen. Given the size of the aneurysm, the patient was offered endovascular treatment. She was quoted a risk of permanent neurological deficit of 3 % or less. Because of the large neck size, a stent-assisted coil embolisation was planned, and the patient was asked to take 75 mg of aspirin and clopidogrel each starting 5 days before the planned procedure. The patient was admitted on the morning of the intervention and clerked by the clinical team. She confirmed having taken her dual antiplatelet therapy as prescribed. She also stated that she was only smoking occasionally, but her frequent absences from the ward suggested higher nicotine consumption on that morning. The procedure was performed under general anaesthetic (GA). However, bronchospasm and a sudden severe drop in blood saturation levels complicated the induction of the anaesthesia. The patient had no background of respiratory problems, and according to the anaesthetist, heavy smoking prior to the GAwas the most likely explanation. A diagnostic angiogram after intubation confirmed the presence of a large left carotid terminus aneurysm (Fig. 1a). No other abnormalities were seen. The patient received IV heparin under ACT monitoring (>250 s), but platelet function inhibition was not tested. Over an exchange wire, a 6-F 90-cm Terumo Destination sheath was placed into the left proximal ICA, and a Fargomax distal access catheter was advanced into the petrous segment of the ICA. This was complicated by vasospasm at the tip of the long sheath, and therefore, 2 mg of nimodipine was added to the saline flush. W. Kuker (*) Department of Neuroradiology, West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK e-mail: wilhelm.kuker@ndcn.ox.ac.uk

Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

Event Abstract Back to Event Denervation-induced homeostatic dendritic plasticity in morphological granule cell models Steffen Platschek1, Hermann Cuntz1, 2, Mario Vuksic1, 3, Thomas Deller1 and Peter Jedlicka1* 1 Goethe University, Institute of Clinical Neuroanatomy, Neuroscience Center, Germany 2 Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany 3 University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Croatia Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease). The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL). ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of passive and/or active membrane properties, the plastic remodeling of dendrites following lesion of entorhinal inputs to granule cells will boost the efficacy of action potential backpropagation significantly and maintain their firing rate. Our results suggest that in addition to synaptic and intrinsic plasticity, a novel form of homeostatic plasticity,structural plasticity due todendritic remodeling.is operating in denervated neurons. Acknowledgements Supported by NSF/BMBF (US-German Collaboration in Computational Neuroscience, No. 01GQ1203A), by Young Investigators Grant (Faculty of medicine, Goethe-University) and by DFG Keywords: electrotonic analysis, Computer Simulation, compartmental modeling, morphological modeling, voltage attenuation, backpropagating action potential, homeostatic plasticity, granule cell Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014. Presentation Type: Poster presentation Topic: morphological and functional characterizations Citation: Platschek S, Cuntz H, Vuksic M, Deller T and Jedlicka P (2014). Denervation-induced homeostatic dendritic plasticity in morphological granule cell models. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Apr 2014; Published Online: 12 Jun 2014. * Correspondence: Dr. Peter Jedlicka, Goethe University, Institute of Clinical Neuroanatomy, Neuroscience Center, Frankfurt, Other, please specify, 60590, Germany, peterjedlicka@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Google Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Google Scholar Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka PubMed Steffen Platschek Hermann Cuntz Mario Vuksic Thomas Deller Peter Jedlicka Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

FAAH-MEDIATED MODULATION OF TLR3-INDUCED NEUROINFLAMMATION IN THE RAT HIPPOCAMPUS

Event Abstract Back to Event FAAH-MEDIATED MODULATION OF TLR3-INDUCED NEUROINFLAMMATION IN THE RAT HIPPOCAMPUS Rebecca J. Henry1, 2*, Daniel M. Kerr1, 2, 3, David P. Finn2, 3 and Michelle Roche1, 2 1 NUIG, Physiology, Ireland 2 NCBES Centre for Pain Research and Neuroscience Centre, Ireland 3 Pharmacology and Therapeutics, School of Medicine, Ireland Several studies have demonstrated that (endo)cannabinoids regulate toll like receptor (TLR)4 induced neuroinflammation, however, there is a paucity of studies investigating their effects on inflammation associated with the activation of other TLRs. The present study examined the effects of inhibiting FAAH, both systemically and centrally, on the expression of TLR3-responsive genes in the rat hippocampus. Animals received systemic or central administration of the FAAH inhibitor URB597 or vehicle, 30 minutes prior to systemic administration of the TLR3 agonist polyI:C or saline. Animals were killed 4 hours post polyI: C and the expression of the interferon’s and cytokines determined using qRT-PCR. Concentrations of anandamide (AEA), 2-arachidonylglycerol (2-AG) and the N-acylethanolamines, N-palmitoylethanolamide (PEA) and N-oleoylethanolamide OEA, were determined using LC-MS-MS URB597 increased hippocampal levels of PEA and OEA, but not AEA or 2-AG. Systemic administration of URB597 increased expression of IFNα and IFNγ, in the presence of polyI:C. The polyI:C-induced increase in IL-1β and TNFα expression were attenuated, while concurrently IL-6 expression was augmented by systemic URB597.In comparison, central administration of URB597 did not alter the expression of the type 1 interferon’s but attenuated the polyI:C-induced increase in IFNγ and IP-10. Furthermore, this treatment regime attenuated the polyI:C-induced increase in TNFα and IL-6 expression, and concurrently increased the IL-10 expression. Taken together, these data demonstrate that increasing FAAH substrates within the brain elicits anti-inflammatory effects which support an important role for FAAH-mediated regulation of TLR3-induced neuroinflammatory responses. Acknowledgements Funding provided by Science Foundation Ireland Research Frontiers Project (Grant no. 11/RFP/NES/3175). Keywords: TLR3, Neuroinflammation, Fatty acid amide hydrolase, Poly I-C, URB597 Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Henry RJ, Kerr DM, Finn DP and Roche M (2014). FAAH-MEDIATED MODULATION OF TLR3-INDUCED NEUROINFLAMMATION IN THE RAT HIPPOCAMPUS. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00024 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Sep 2014; Published Online: 15 Sep 2014. * Correspondence: Ms. Rebecca J Henry, NUIG, Physiology, Galway, Ireland, r.henry2@nuigalway.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rebecca J Henry Daniel M Kerr David P Finn Michelle Roche Google Rebecca J Henry Daniel M Kerr David P Finn Michelle Roche Google Scholar Rebecca J Henry Daniel M Kerr David P Finn Michelle Roche PubMed Rebecca J Henry Daniel M Kerr David P Finn Michelle Roche Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Keynote Address: Integrating Time and Repetition; The Psychophysiology of Temporal Processing.

Event Abstract Back to Event Keynote Address: Integrating Time and Repetition; The Psychophysiology of Temporal Processing. Timothy W. Budd1* 1 University of Newcastle, School of Psychology, Australia Temporal processing typically refers to our ability to resolve information conveyed within the time-varying properties of sensory stimulation. This unique ability allows us to form a dynamic and coherent perceptual representation of the environment as well as forming the basis for multisensory integration and music and speech perception. In this talk I will review evidence from a range of psychophysiological studies which provide support for the proposal that a better understanding of the complex neural mechanisms underlying temporal processing can be gained by examining the fundamental interaction between time and repetition on sensory measures of brain activity. The focus will be on studies that directly examine the correspondence between perceptual (psychophysical) and neurophysiological measures (EEG, ERP and fMRI) that are exquisitely sensitive to interactions between experimental manipulations of time and repetition. This review will include evidence from human studies in both normal and clinical populations, where a primary dysfunction in the neural mechanisms underlying temporal processing is implicated, as well as corresponding neurophysiological evidence from recent animal studies. Traditional neurophysiological and perceptual models of temporal processing will be evaluated and key emerging approaches described. Directions for future research that offer the potential to capitalise on recent advances in analytic methods in psychophysiology as well as conceptual developments will also be discussed. Acknowledgements This research reviewed in this address was supported by the Schizophrenia Research Institute utilizing infrastructure funding from NSW Health,the University of Newcastle Research Grants committee,the Hunter Medical Research Institute, the Priority Research Centre for Translational Neuroscience and Mental Health and the School of Psychology,The University of Newcastle, Australia. Keywords: Temporal Processsing, Stimulus Interval, Stimulus Repetition, EEG, ERP, fMRI, Schizophrenia, Mulitsensory Integration, autism, adolescence Conference: Australasian Society for Psychophysiology, Inc, Coffs Harbour, Australia, 26 Nov - 28 Nov, 2014. Presentation Type: Oral Presentation Topic: Psychophysiology Citation: Budd TW (2014). Keynote Address: Integrating Time and Repetition; The Psychophysiology of Temporal Processing.. Conference Abstract: Australasian Society for Psychophysiology, Inc. doi: 10.3389/conf.fnhum.2014.216.00037 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Nov 2014; Published Online: 03 Dec 2014. * Correspondence: Dr. Timothy W Budd, University of Newcastle, School of Psychology, Ourimbah, New South Wales, 2258, Australia, bill.budd@newcastle.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Timothy W Budd Google Timothy W Budd Google Scholar Timothy W Budd PubMed Timothy W Budd Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Differential gating of dendritic spikes by compartmentalized inhibition

Differential gating of dendritic spikes by compartmentalized inhibition

Word Definition Ability in Patients with Alzheimer's disease

Sunghee Lim, M.A.*, Miseon Kwon, Ph.D.†, Hyun-Sub Sim, Ph.D.‡, SangYun Kim, M.D., Jun-Young Lee, M.D. Department of Physical Medicine and Rehabilitation*, Korea University Anam Hospital, Seoul; Department of Neurology†, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Department of Communication Disorders‡, Ewha Womans University, Seoul; Department of Neurology§, Seoul National University College of Medicine & Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam; Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea

Investigating the bundle compliance of IVIG delivery in the Greater Manchester Neuroscience centre.

Salford Royal Hospital is one of the largest users of IVIG for chronic neurological illnesses within the UK. The majority of patients are being treated for chronic inflammatory polyneuropathy and multifocal motor neuropathy. We hypothesised that the components of care being delivered to these patients differed to our stated standard of care (IVIG care bundle). We performed a service review exercise to identify shortcomings and improve quality of patient care. The aim was to measure overall bundle compliance being delivered to 75 patients with a view to improving the overall quality of care being delivered in the future. A retrospective case note study was carried out to measure compliance with the 17 areas of care, which constituted the IVIG bundle. Nine areas of care were being delivered to all 75 patients. This meant that all patients were receiving three monthly bloods, a documented cannula pathway, a filed prescription, a medical assessment, and the correct follow-up. Not all patients had a filed consent form, ECG or HAT assessment and an even smaller number of patients had a documented calculation for the amount of IVIG that needed to be given and few had a serum save. No patient in the group was receiving the intended complete bundle of care.The results led to the development of an electronic treatment dashboard for the delivery of chronic IVIG therapy to this group. A re-audit has shown that rates of individual areas of care being delivered has increased markedly but overall compliance has only increased a slightly due to a lack of serum saves for patients.

Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats

Event Abstract Back to Event Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats Carol L. Naughton1, 2, 3, Deirdre B. Hoban1, 2, 3, Ruth M. Concannon1, 2, 3, Jennifer Feehan1, Aoife McNulty1, Niamh Moriarty1, Deirdre Rooney1 and Eilís Dowd1, 2, 3* 1 National University of Ireland, Galway, Pharmacology & Therapeutics, Ireland 2 Galway Neuroscience Centre, Ireland 3 National Centre for Biomedical Engineering and Science, NUI Galway, Ireland Background: For almost 50 years, Parkinson’s disease has been modelled in preclinical animals using selective catecholaminergic neurotoxins such as 6-hydroxydopamine and MPTP. However, because these models bear little etiological resemblance to the human condition, more recently, there has been a considerable drive to develop and characterise models with improved validity for the human condition. Two such models are those induced by the bacterial inflammagen, LPS, and the organic pesticide, rotenone. However, these models have been poorly characterised with respect to more established models. Aim: Thus, the aim of this project was to characterise the motor impairments induced by LPS and rotenone with those induced by the classic neurotoxin, 6-hydroxydopamine. Methods: Twenty four male Sprague Dawley rats underwent baseline testing on a variety of tests of lateralised motor function (the Stepping Test, the Whisker Test, the Corridor Test and the Cylinder Test). The rats were then performance-matched into 3 groups for unilateral intrastriatal infusion of 6-hydroxydopamine (28 g, n=8), LPS (20 g, n=8) or rotenone (3.6 g, n=8). Motor testing resumed on the day after lesion surgery and continued for ten weeks. Rats were also tested for amphetamine-induced rotational asymmetry three weeks after lesion surgery. Immunohistochemistry for neurodegeneration, microgliosis and astrocytosis was also performed. Results: Unilateral intra-striatal infusion of all three neurotoxins induced a significant impairment in contralateral motor function which was evident from the first day post lesion. However, the impairment induced by 6-hydroxydopamine was significantly more pronounced and stable than that induced by the other neurotoxins. When the rats were tested for amphetamine-induced rotation (which is the classic test for dopaminergic asymmetry), it was found that the 6-hydroxydopamine and rotenone-lesioned rats rotated significantly in the ipsilateral direction, while LPS-lesioned rats did not rotate at all. There was significant neurodegeneration, microgliosis and astrocytosis in all experimental groups on the side ipsilateral to the lesion. Conclusions: This study demonstrates that there are key differences in the patterns of motor dysfunction induced by different Parkinsonian neurotoxins and their associated neurodegenerative effects. These differences should be taken into consideration when selecting the most appropriate model for Parkinson’s disease preclinical studies. Acknowledgements The authors would like to thank Ms. Kiah McCabe for technical assistance. Keywords: animal models of neurodegenerative disease, lipopolysaccharide, 6-hydroxydopamine, Rotenone, Animal behavioral models Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Oral Presentation Topic: Early Career Neuroscience Citation: Naughton CL, Hoban DB, Concannon RM, Feehan J, McNulty A, Moriarty N, Rooney D and Dowd E (2014). Title Comparative assessment of the motor dysfunction induced by neurotoxic, inflammatory and environmental Parkinson’s disease-related neurotoxins in rats . Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00028 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Sep 2014; Published Online: 15 Sep 2014. * Correspondence: Dr. Eilís Dowd, National University of Ireland, Galway, Pharmacology & Therapeutics, Galway, Ireland, eilis.dowd@nuigalway.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd Google Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd Google Scholar Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd PubMed Carol L Naughton Deirdre B Hoban Ruth M Concannon Jennifer Feehan Aoife McNulty Niamh Moriarty Deirdre Rooney Eilís Dowd Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The language of visual representations in the neurosciences — relating past and future

AbstractIn theoretical accounts of the neurosciences, investigative research programs have often been separated into the morphological and physiological tradition. The morphological tradition is seen as describing the structure and form of the external and interior parts of the brain and spinal cord. The physiological tradition is interpreted as a compilation of those approaches which investigate cerebral functions particularly in their dynamic interactions. It must be regarded as an open question, though, whether the distinction between the morphological and physiological tradition in modern clinical and basic neuroscience has now become obsolete with the most recent neuroimaging techniques, such as fMRI, PET scans, SPECT, etc. Taken at face value, these new imaging techniques seem to relate, overlap, and even identify the anatomical with the functional substrate, when mapping individual patterns of neural activity across the visually delineated morphological structures. The particular focus of this review article is primarily on the morphological tradition, beginning with German neuroanatomist Samuel Thomas Soemmerring and leading to recent approaches in the neurohistological work of neuroscience centres in the United States and morphophysiological neuroimaging techniques in Canada. Following some landmark research steps in neuroanatomy detailed in the first section, this article analyzes the changing trajectories to an integrative theory of the brain in its second section. An examination of the relationship between form and function within the material culture of neuroscience in the third and final part, will further reveal an astonishingly heterogeneous investigative and conceptual terrain.

Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease

Event Abstract Back to Event Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease Deirdre B. Hoban1, 2, Linda Howard3 and Eilis Dowd1, 2* 1 National University of Ireland, Galway, Pharmacology & Therapeutics, Ireland 2 NCBES Galway Neuroscience Centre, Ireland 3 National University of Ireland, Galway, Regenerative Medicine Institute (REMEDI), Ireland The delivery method of GDNF has hampered its efficacy as a neuroprotectant in Parkinson’s disease(PD). Ex vivo gene therapy, in which suitable cells, such as bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress GDNF prior to transplantation may be more beneficial for GDNF delivery than direct brain infusion of the neurotrophin. In this study, we used an inflammatory model of PD (the lipopolysaccharide model) to assess the ability of transplanted GDNF-GFP-MSCs to protect against LPS-induced neuroinflammation, neurodegeneration and behavioural impairment. 30 male Sprague Dawley rats were used in this experiment. Motor performance was assessed daily using Stepping and Whisker tests pre- and post-surgery. Rats were performance matched into 3 groups (LPS, LPS + GFP-MSCs, LPS + GDNF-GFP-MSCs; n=10/group). Both cell groups received a transplant of either 200,000 GFP-MSCs or 200,000 GDNF-GFP-MSCs. One day post-transplantation, all rats received a unilateral infusion of LPS (10µg in 2µl sterile saline) into the substantia nigra. Rats were sacrificed by transcardial perfusion-fixation and their brains processed for post-mortem quantitative immunohistochemistry. Injection of LPS into the substantia nigra induced a pronounced inflammatory response which resulted in 20% loss of nigrostriatal dopaminergic neurons and a mild, transient effect on contralateral motor dysfunction. While neither GFP-MSCs nor GDNF-GFP-MSCs transplanted into the striatum protected against motor dysfunction or the nigrostriatal pathway as a whole, dense areas of TH-staining proximal to the transplant site were observed. Importantly, this effect was observed only in the GDNF-GFP-MSC transplanted group. This demonstrates protection and/or sprouting of the dopaminergic terminals induced by trophic effects of secreted GDNF in the LPS-lesioned rats and thus highlights the potential of ex vivo gene therapy using GDNF-GFP-MSCs. Acknowledgements This research was funded by Science Foundation Ireland (11/RFP/NES/3183). Keywords: Lipopolysaccharides, Neuroinflammation, neurodegeneration, Parkinson's disease, Glial Cell Line-Derived Neurotrophic Factor, Neuroprotection Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Poster Presentation Topic: Early Career Neuroscience Citation: Hoban DB, Howard L and Dowd E (2014). Assessment of the neurotrophic effects exerted by GDNF following delivery of neurotrophin-secreting stem cells to the rat brain in the lipopolysaccharide model of Parkinson’s disease. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00019 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Sep 2014; Published Online: 12 Sep 2014. * Correspondence: Dr. Eilis Dowd, National University of Ireland, Galway, Pharmacology & Therapeutics, Galway, Ireland, eilis.dowd@nuigalway.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Deirdre B Hoban Linda Howard Eilis Dowd Google Deirdre B Hoban Linda Howard Eilis Dowd Google Scholar Deirdre B Hoban Linda Howard Eilis Dowd PubMed Deirdre B Hoban Linda Howard Eilis Dowd Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

AN INVESTIGATION OF GLOBAL NETWORK STRUCTURE IN BIPOLAR DISORDER

Event Abstract Back to Event AN INVESTIGATION OF GLOBAL NETWORK STRUCTURE IN BIPOLAR DISORDER Stefani O'Donoghue1, 2*, Louise Emsell1, 3, Camilla Langan1, Natalie Forde1, 4, Dara M. Cannon1, 2, 5 and Colm McDonald1, 2 1 National University of Ireland, Galway, Psychiatry, Ireland 2 National University of Ireland, Galway, Galway Neuroscience Center, Ireland 3 University Hospitals Leuven, Belgium, KU Leuven & Radiology, Belgium 4 University Medical Centre Groningen, the Netherlands., Psychiatry, Netherlands 5 National University of Ireland, Galway, Anatomy, Ireland Introduction: Network analysis is a novel technique used to identify brain connectivity patterns. Metrics of integration and segregation allow for brain networks to be quantified into neurobiologically meaningful measures. Aim: This study utilises graph theory metrics to investigate properties of brain communication, as well as permutation testing to determine cluster based effects between groups. This analysis aims to elucidate disrupted anatomical wiring as an attribute of psychiatric illness. Methods: Participants were recruited as part of the Galway Bipolar Study (43 Healthy Controls & 42 subjects with Euthymic Bipolar Disorder). Diffusion MRI data was acquired on a 1.5 Tesla Scanner. Connectivity matrices were produced using ExploreDTI. Network metrics were generated using the Brain Connectivity Toolbox in MATLAB. The Network Based Statistic toolbox is a method to identify an experimental effect at the cluster level. FWER corrected p-values are calculated for each component using permutation testing. Results: Properties of integration and segregation revealed between group differences in metrics of Characteristic Path Length [p=0.017], Global Efficiency [p=0.015] and Clustering Coefficient [p=0.047]; with greater brain network disorganization in patients relative to controls. Network analysis was carried out through the NBS with M= 5000 permutations at p< 0.05, revealing a contrast in patients relative to controls across varying (t-statistic) thresholds[(t=2, p=0.015); (t=2.5, p=0.017); (t=3, p=0.020)], in which a single disconnected sub-network comprising multiple dysconnections was identified for each threshold. Conclusion: Metrics that characterize brain communication revealed greater disorganization in patients relative to controls. The NBS findings demonstrated consistency across t-statistic thresholds among occipital and default mode network regions. This study, applying novel network based statistics to MRI and DTI data, indicates that disrupted neuranatomical connectivity is a trait based feature of bipolar disorder. Acknowledgements This research was supported by the Hardiman Research Scholarship. We gratefully acknowledge the participants of this study and the radiographers of the University College Hospital Galway Magnetic Resonance Imaging department for their support during data collection.

Pronounced upregulation of the microglial CB2 receptor in an inflammation driven rat model of Parkinson’s disease: Implications for anti-inflammatory disease modification

Event Abstract Back to Event Pronounced upregulation of the microglial CB2 receptor in an inflammation driven rat model of Parkinson’s disease: Implications for anti-inflammatory disease modification Ruth M. Concannon1, 2, Bright N. Okine1, 2, David P. Finn1, 2 and Eilis Dowd1, 2* 1 National University of Ireland Galway, Pharmacology & Therapeutics, Ireland 2 National University of Ireland Galway, NCBES Galway Neuroscience Centre, Ireland The endocannabinoid system has recently emerged as a potential anti-inflammatory target to break the self-sustaining cycle of neuroinflammation and neurodegeneration that is associated with neurodegenerative diseases. However, in order to facilitate the investigation of cannabinoid drugs in neurodegenerative disease, the changes that occur in the endocannabinoid system in response to different degenerative triggers needs to be elucidated. Therefore, the aim of this study was to investigate and compare the changes that occur in the endocannabinoid system in neurotoxic and inflammation-driven models of Parkinson’s disease. Male Sprague Dawley rats were given a single, intra-striatal injection of the dopaminergic neurotoxin, 6-hydroxydopamine, or the bacterial inflammagen, lipopolysaccharide (LPS). Animals underwent behavioural testing for motor dysfunction on Days 7, 14 and 28 days, and were sacrificed on Days 1, 4, 14 and 28 post-surgery (n=8 per treatment, per timepoint). Changes in the endocannabinoid system were investigated by qRT-PCR, mass spectrometry and immunohistochemistry. Following injection of 6-hydroxydopamine or LPS into the rat striatum, we found that expression of the cannabinoid type 2, (CB2) receptor was significantly elevated which correlated significantly with an increase in microglial activation. Interestingly, the increase in CB2 receptor expression in the inflammation-driven model was significantly more pronounced than that in the neurotoxic model. Moreover, elevation of striatal endocannabinoid levels was also observed in the LPS model but not the 6-hydroxydopamine model. Thus, this study has shown that the endocannabinoid system is dysregulated in different models of Parkinson’s disease, and has also revealed significant differences between the models themselves. This study indicates that targeting the CB2 receptor may represent a viable target for anti-inflammatory disease modification in Parkinson’s disease. Acknowledgements The authors gratefully acknowledge the support of Irish Health Research Board Grant no. (HRA_POR/2012/12). Keywords: CB2 receptor, endocannabinoid system, Parkinson Disease, Neuroinflammation, animal model Conference: Neuroscience Ireland Young Neuroscientists Symposium 2014 , Dublin, Ireland, 20 Sep - 20 Sep, 2014. Presentation Type: Oral Presentation Topic: Early Career Neuroscience Citation: Concannon RM, Okine BN, Finn DP and Dowd E (2014). Pronounced upregulation of the microglial CB2 receptor in an inflammation driven rat model of Parkinson’s disease: Implications for anti-inflammatory disease modification. Front. Neurosci. Conference Abstract: Neuroscience Ireland Young Neuroscientists Symposium 2014 . doi: 10.3389/conf.fnins.2014.87.00025 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Sep 2014; Published Online: 15 Sep 2014. * Correspondence: Dr. Eilis Dowd, National University of Ireland Galway, Pharmacology & Therapeutics, Galway, Ireland, eilis.dowd@nuigalway.ie Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ruth M Concannon Bright N Okine David P Finn Eilis Dowd Google Ruth M Concannon Bright N Okine David P Finn Eilis Dowd Google Scholar Ruth M Concannon Bright N Okine David P Finn Eilis Dowd PubMed Ruth M Concannon Bright N Okine David P Finn Eilis Dowd Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Research Highlights: Highlights from the Latest Articles in Regenerative Medicine

Regenerative MedicineVol. 9, No. 1 News & ViewsResearch Highlights: Highlights from the latest articles in regenerative medicineAmber Kerstetter-Fogle, Eleftherios Sachlos & Thomas BollenbachAmber Kerstetter-FogleCase Western Reserve University, Center for Translational Neuroscience, Department of Neurological Surgery, Cleveland, OH 44106, USA. Search for more papers by this authorEmail the corresponding author at aek20@case.edu, Eleftherios SachlosStem Cell & Cancer Research Institute, McMaster University, ON, Canada. Search for more papers by this authorEmail the corresponding author at sachlos@mcmaster.ca & Thomas BollenbachOrganogenesis, Preclinical Research & Development, 150 Dan Road, Canton, MA 02021, USA. Search for more papers by this authorEmail the corresponding author at tbollenbach@organo.comPublished Online:18 Dec 2013https://doi.org/10.2217/rme.13.85AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleFiguresReferencesRelatedDetails Vol. 9, No. 1 Follow us on social media for the latest updates Metrics Downloaded 80 times History Published online 18 December 2013 Published in print January 2014 Information© Future Medicine LtdPDF download

Correction: Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis

The correct address for Prof. Carlos Matute is: Achucarro Basque Center for Neuroscience, CIBERNED and Departamento de Neurociencias, Universidad del Pais Vasco, Leioa, Spain. There was an error in the last sentence of the eighth paragraph of the Discussion section. The corrected sentence should read: “Interestingly, it has been recently shown that BBG but not oATP is a potent inhibitor of Pannexin1 channels [50,51].” Reference [51] should be updated to: Wang J, Jackson DG, Dahl G (2013) The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1. J Gen Physiol 141(5):649-656.

The effectiveness of specialist neuroscience care in severe traumatic brain injury: A systematic review

Background. UK trauma services are currently undergoing reconfiguration, but the optimum management pathway for head-injured patients is uncertain. We therefore performed a systematic review to assess the effects of routine inter-hospital transfer and specialist neuroscience care on mortality and disability in patients with non-surgical severe traumatic brain injury injured nearest to a non-specialist acute hospital. Methods. A protocol was registered with PROSPERO (CRD42012002021) and review methodology followed Cochrane Collaboration recommendations. A peer reviewed search strategy was implemented in an exhaustive range of information sources, including all major bibliographic databases, between 1973 and July 2013. Selection of eligible studies, extraction of relevant data and bias assessment were then performed by two independent reviewers. In the absence of homogeneous effect estimates at low risk of bias a narrative synthesis was pre-specified. Results. Four cohort studies, including a total of 4688 patients, were identified as potentially eligible after screening and bias assessment. Confounding by indication, arising from selective transfer of less severely injured patients, was the main limitation of included studies, with overall risk of bias rated as high for both mortality and disability effect estimates. Adjusted odds ratios for mortality favoured secondary transfer, ranging from 1.92 (95% CI 1.25–2.95) to 2.09 (95% CI 1.59–2.74). No convincing association was observed between non-specialist care and unfavourable outcome with a conditional odds ratio of 1.13 (95% CI 0.36–3.6). Conclusions. There is limited evidence supporting a strategy of secondary transfer of severe non-surgical traumatic brain injury patients to specialist neuroscience centres. Randomised controlled trials powered to detect clinically plausible treatment effects should be considered to definitively investigate effectiveness.

Response to Keating and Rossell

Back to table of contents Previous article Next article Communications and UpdatesFull AccessResponse to Keating and RossellGuido K. Frank, M.D., Megan E. Shott, B.S., Jennifer O. Hagman, M.D., and Vijay A. Mittal, Ph.D.Guido K. FrankSearch for more papers by this author, M.D., Megan E. ShottSearch for more papers by this author, B.S., Jennifer O. HagmanSearch for more papers by this author, M.D., and Vijay A. MittalSearch for more papers by this author, Ph.D.Published Online:1 Nov 2013https://doi.org/10.1176/appi.ajp.2013.13060813rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The correlation between gyrus rectus volume and sweet taste pleasantness in the comparison group is striking as it supports the previous literature and is consistent with an important concept established by the works of Rolls, Kringelbach, and others (1). All eating disorder groups in our sample showed increased gyrus rectus volume relative to individuals in the comparison group, suggesting comparable pathophysiology. Groups were combined for that reason, and we did find a positive correlation between sweet taste pleasantness and volume in the eating disorder case subjects. In addition, within eating disorder subgroups, each individual group showed a positive correlation (anorexia nervosa, r=0.120; bulimia nervosa, r=0.287; recovered anorexia nervosa, r=0.345) between sweet taste pleasantness and gyrus rectus volume, supporting the idea that analyzing the groups as a whole was valid. The correlation coefficients were modest. Despite a significant amount of research, we still know little about the connection between brain structure and function and these results are a step toward identifying target areas that could contribute to altered food intake. Taste pleasantness in individuals with eating disorder could be less well mapped (yet still positively) onto gyrus rectus neurons due to the altered volume, and this could interfere with correct value computation.It is important to view eating disorders as complex problems with a variety of factors that most likely contribute to development and then perpetuation of the illnesses. Expecting direct correlations between all those measures would be overly simplistic, and we believe that dissecting eating disorders by brain circuits that may contribute to the psychopathology will be more fruitful. Trait alterations seem to exist that cause heightened sensitivity to various (food- and nonfood-related) rewarding or punishing stimuli, contributing to a sense of instability across individuals with anorexia and bulimia nervosa (2, 3). This instability may contribute to heightened anxiety and intolerance of uncertainty (4). Additionally, as suggested in this study, there may be developmental factors such as altered brain volume in the orbitofrontal cortex that could interfere with the processing of value of food stimuli. We recently published a similarly designed study in adolescents with anorexia nervosa and found similarly larger gyrus rectus volumes, further supporting that this structure could be involved in the pathophysiology of eating disorders (5).All eating disorder groups share an enlarged gyrus rectus, which could impair a healthy sensory satiety processing. In fact individuals with eating disorders share many similar behaviors but on different scales, and there is overlap in symptoms not only across subgroups but even depending on stage of recovery. For instance, individuals with bulimia nervosa are often able to restrict food intake in-between binge episodes. Furthermore, many individuals who meet criteria for one category of eating disorder will often shift into another eating disorder during the course of illness, which is consistent with a common vulnerability.From the Department of Psychiatry, School of Medicine, University of Colorado Anschutz Medical Campus; and the Center for Neuroscience, Department of Psychology and Neuroscience, University of Colorado Boulder.The authors’ disclosures accompany the original article.References1 Kringelbach ML, O’Doherty J, Rolls ET, Andrews C: Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb Cortex 2003; 13:1064–1071Crossref, Medline, Google Scholar2 Frank GK, Reynolds JR, Shott ME, O’Reilly RC: Altered temporal difference learning in bulimia nervosa. Biol Psychiatry 2011; 70:728–735Crossref, Medline, Google Scholar3 Jappe LM, Frank GK, Shott ME, Rollin MD, Pryor T, Hagman JO, Yang TT, Davis E: Heightened sensitivity to reward and punishment in anorexia nervosa. Int J Eat Disord 2011; 44:317–324Crossref, Medline, Google Scholar4 Frank GK, Roblek T, Shott ME, Jappe LM, Rollin MD, Hagman JO, Pryor T: Heightened fear of uncertainty in anorexia and bulimia nervosa. Int J Eat Disord 2012; 45:227–232Crossref, Medline, Google Scholar5 Frank GK, Shott ME, Hagman JO, Yang TT: Localized brain volume and white matter integrity alterations in adolescent anorexia nervosa. J Am Acad Child Adolesc Psychiatry 2013 (in press)Crossref, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 170Issue 11 November 2013Pages 1367-1367 Metrics PDF download History Accepted 1 September 2013 Published online 1 November 2013 Published in print 1 November 2013

Attenuated negative symptoms in individuals at clinical high risk for psychosis

Attenuated negative symptoms in individuals at clinical high risk for psychosis D.L.Demmin, R.E. Carrion, A. Auther, D.McLaughlin, B.A. Cornblatt a,b,c Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore – Long Island Jewish Health System (NS-LIJHS), Glen Oaks, NY, USA Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, North Shore – Long Island Jewish Health System, Manhasset, NY Department of Psychiatry and Molecular Medicine, Hofstra North ShoreLIJ School of Medicine, Hempstead, NY

Research Highlights: Highlights from the Latest Articles in Regenerative Medicine

Regenerative MedicineVol. 8, No. 6 News & ViewsResearch Highlights: Highlights from the latest articles in regenerative medicineAmber E Kerstetter-FogleAmber E Kerstetter-FogleCase Western Reserve University, Center for Translational Neuroscience, Department of Neurological Surgery, Cleveland, OH 44106, USA. Search for more papers by this authorEmail the corresponding author at aek20@case.eduPublished Online:22 Oct 2013https://doi.org/10.2217/rme.13.72AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleFiguresReferencesRelatedDetails Vol. 8, No. 6 Follow us on social media for the latest updates Metrics Downloaded 46 times History Published online 22 October 2013 Published in print November 2013 Information© Future Medicine LtdPDF download

Therapeutic sedation for functional (psychogenic) neurological symptoms

BackgroundPatients with severe functional (psychogenic) neurological symptoms such as paralysis and fixed dystonia present a therapeutic challenge, particularly if no movement is possible during physiotherapy. Sedation has been discussed as a treatment for functional neurological symptoms for 100years but technique, use of video and outcome has not been systematically described. MethodsTherapeutic sedation of patients with severe functional neurological symptoms with propofol and follow up at a neuroscience centre. ResultsOf eleven patients (median duration 14months), five were cured or had major improvement with sedation. At follow up (median 30months) four were asymptomatic, two were significantly improved and one had minor improvements. We describe a standardized anesthetic and physician technique, refined over consecutive treatments. ConclusionIn carefully chosen patients, therapeutic sedation with propofol can be a useful adjunctive treatment for patients with severe functional neurological symptoms. The treatment deserves randomized evaluation.

Do Prolonged Primary Transport Times for Traumatic Brain Injury Patients Result in Deteriorating Physiology? A Cohort Study

Background. Recent interest has focused on reorganizing emergency medical services (EMS) for traumatic brain injury (TBI) patients, with bypass of nonspecialist hospitals and direct transportation to distant neuroscience centers. Although this could expedite neurosurgery and neurocritical care, deteriorating physiology could be deleterious. Methods. We performed a multicenter cohort study examining adult patients with significant TBI enrolled in the English National Trauma Registry. The distributions and correlation of first recorded prehospital and emergency department (ED) vital signs were compared, and the effect of time on changes in vital signs was examined in bivariate and multivariate analyses. Results. A total of 7149 eligible patients were studied. No clinically significant differences were apparent between distributions of prehospital and ED vital signs. Moderate linear correlation was observed for field and ED pulse rate (r2 = 0.34) and GCS values (Spearman's rho = 0.76), with weak correlation apparent for systolic blood pressure (r2 = 0.28) and respiratory rate (r2 = 0.28). Eight percent of cases’ vital signs deteriorated in the prehospital interval; however, odds of deterioration in vital sign status did not vary significantly with duration of EMS interval. Conclusion. The similarity between prehospital and ED vital signs, and lack of association between EMS interval and physiological deterioration, may support a strategy of direct transportation of TBI cases to specialist centers. Further research is necessary to identify patients at risk from deterioration during bypass and to investigate effects on mortality.