CIR-Myo News: Abstracts of the 2015 Spring Padua Muscle Days

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Analyse neurochimique des dépolarisations corticales envahissantes après un traumatisme crânien sévère : existe-il un continuum entre une réponse physiologique et une crise métabolique?

“Traumatic brain injury” (TBI) encompasses a heterogeneous group of physio-pathological phenomenon. Prognosis, clinical course evaluation and treatment of brain trauma remain challenging. Brain damage results from both the initial physical insult (primary injury), and also continues to occur in the ensuing hours to days because of secondary brain aggressions. Among secondary injuries following TBI, Cortical Spreading Depolarizations (CSD) have emerged since the mid-90s. CSD are waves of depolarization propagating along the cortex at a speed of 1-5 mm/min that induced a massive energetic demand to repolarize the cells. CSD are participating to prognosis because their occurrence and duration are related to outcome in different acute brain injuries (TBI, sub-arachnoid hemorrhage and ischemic stroke). During my thesis, our main goal was to determine whether the CSD reinforced neuronal death following brain trauma that can explain the poor prognosis. In a first study we delineated brain regions where neuronal death occurs following lateral fluid percussion injury (LFPI) in order to record CSDs in this area. Then, as we wanted to assess the energetic balance of this tissue during CSD using biosensors, we had primarily to check for the biosensor reliability to oxygen (O2) and temperature (To). As oxygen and temperature were different from bench (in vitro) to bedside (in vivo) monitoring, we developed algorithms to compute offline the in vivo values obtained for glucose, lactate or glutamate brain concentrations respecting the local O2 concentrations and To measured in the cortex. Finally, using the biosensors, we described the dynamic real time metabolic changes occurring after CSDs in 3 conditions: A healthy cortex, an injured cortex after LFPI, and when CSD occurred in cluster after LFPI. Although the normal brain displayed a hyper-glycolytic state following CSD (transient low glucose concentrations + prolonged elevated lactate concentrations), TBI tissue exhibited a different pattern that could be metabolic crisis (very low glucose concentrations + normal to low lactateconcentrations)Les traumatismes crâniens (TC) représentent la première cause de décès ou de handicap avant l'âge de 45 ans, avec une incidence en Europe de 235/100 000 habitants. Chez les patients survivant à un TC, les séquelles sont fréquentes allant de l'état végétatif chronique au syndrome post-concussionnel compliquant principalement la réinsertion socio professionnelle et familiale des victimes. Cependant la nature des lésions cérébrales provoquées par un TC est encore mal connue et les thérapies susceptibles d'empêcher la progression des lésions neurologiques sont très limitées. Un TC provoque d'abord des lésions directement dues à l'impact (lésions primaires). D'autres mécanismes secondaires vont avoir lieu dès les premières minutes suivant le TC et peuvent évoluer sur plusieurs jours. Elles sont susceptibles d'être atténuées par une thérapeutique appropriée et sont donc l'objet de la plupart des efforts de recherche actuels. Néanmoins, notre connaissance de ces phénomènes d'agression primaires et secondaires, est incomplète et ne permet pas d'expliquer correctement l'évolution des TC. Les dépolarisations corticales envahissantes (DCE) ou cortical spreading depolarizations””sont un des évènements délétères contribuant aux lésions secondaires consécutives au TC. Les DCE sont des vagues de dépolarisation massive associées à un mauvais pronostic. Elles sont caractérisées par une dépression de l'activité electrocorticographique et une dépolarisation des neurones corticaux et des astrocytes qui se propagent sur le cortex. Les DCE s'accompagnent d'une augmentation des besoins métaboliques visant à restituer au tissu son état d'homéostasie neurochimique et de polarisation cellulaire. Les conséquences des DCE sur le métabolisme cérébral sont encore mal connues aussi bien sur un tissu sain qu'après agression cérébrale. Il existe des arguments pour penser que l'incidence, le nombre et la durée des DCE sont associés à un moins bon pronostic chez l'homme après agression cérébrale. Cependant, les mécanismes par lesquels ces DCE auraient une toxicité directe reposent encore sur des arguments le plus souvent indirects et sont mal compris. L'objectif principal de ce travail de thèse a été de caractériser les conséquences neurochimiques et micro-vasculaires des DCE afin de mieux comprendre leur physiopathologie dans un cortex sain ou agressé par un TC sévèr

Influence of repetitive transcranial magnetic stimulation on expression of brain derived neurotrophic factor, glutamate transporters and oxidative status in selectively vulnerable brain structures in rat

Uticaj repetitivne transkranijalne magnetne stimulacije (rTMS) na obim i kvalitet celularnih i subcelularnih promena u mozgu je nedovoljno poznat. Pokazano je da oblik rTMS- stimulacija teta praskovima (eng. theta burst stimulation; TBS) podstiče procese nalik dugotrajnoj potencijaciji i dugotrajnoj depresiji, koji se nalaze u osnovi sinaptičke plastičnosti. Među faktorima koji su značajni u indukciji i održavanju sinaptičke plastičnosti ističu se neurotrofični faktor moždanog porekla (eng. brain derived neurotrophic factor, BDNF), ekspresija vezikularnih i membranskih glutamatnih transportera koji podržavaju funkciju i promet glutamata, kao i oksidativno stanje neuralnih komponenti, koje je pokazatelj stepena i kvaliteta iskorišćavanja kiseonika i održavanja metaboličkih procesa u optimalnom okviru. S obzirom da se tehnikama rTMS direktno može uticati na povećanje, odnosno smanjenje nadražljivosti mozga i time pokrenuti promene sinaptičke plastičnosti, studija se bavila uticajem ovakve vrste stimulacije na ekspresiju BDNF, ekspresiju membranskih i vezikularnog glutamatnog transportera, kao i nivo prooksidativnih i antioksidativnih biohemijskih pokazatelja u moždanim regionima koji bi po svojim strukturnim i funkcionalnim karakteristikama mogli biti izmenjen

IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)

Magnetoencephalography (MEG) records weak magnetic fields outside the human head and thereby provides millisecond-accurate information about neuronal currents supporting human brain function. MEG and electroencephalography (EEG) are closely related complementary methods and should be interpreted together whenever possible. This manuscript covers the basic physical and physiological principles of MEG and discusses the main aspects of state-of-the-art MEG data analysis. We provide guidelines for best practices of patient preparation, stimulus presentation, MEG data collection and analysis, as well as for MEG interpretation in routine clinical examinations. In 2017, about 200 whole-scalp MEG devices were in operation worldwide, many of them located in clinical environments. Yet, the established clinical indications for MEG examinations remain few, mainly restricted to the diagnostics of epilepsy and to preoperative functional evaluation of neurosurgical patients. We are confident that the extensive ongoing basic MEG research indicates potential for the evaluation of neurological and psychiatric syndromes, developmental disorders, and the integrity of cortical brain networks after stroke. Basic and clinical research is, thus, paving way for new clinical applications to be identified by an increasing number of practitioners of MEG. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.Peer reviewe

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40