Name: modeling neural immune signaling of episodic and chronic migraine using spreading depression in vitro
Uploaded: 2011-06-13T13:00:00
Duration: 16 min 13 s
Description: Watch this Scientific Journal Video about Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro at JoVE.com

Эта работа была поддержана грантами Национального института неврологических расстройств и инсульта (NS-19108), Национальным институтом детского здоровья и болезни (PO1-HD09402), Фонд Мигрень исследований и Белый Foundation. Г-жа Марсия П. Kraig помощь в подготовке и поддержании культуры систем.

<ol>
	<li>Kunkler, P. E., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calcium+waves+precede+electrophysiological+changes+of+spreading+depression+in+hippocampal+organ+cultures.">Calcium waves precede electrophysiological changes of spreading depression in hippocampal organ cultures.</a> J Neurosci. 18 (9), 3416-3425 (1998).</li><li>Kunkler, P. E., Hulse, R. E., Schmitt, M. W., Nicholson, C., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+current+source+density+analysis+in+hippocampal+organotypic+culture+shows+that+spreading+depression+occurs+with+uniquely+reversing+currents.">Optical current source density analysis in hippocampal organotypic culture shows that spreading depression occurs with uniquely reversing currents.</a> J Neurosci. 25 (15), 3952-3961 (2005).</li><li>Hulse, R. E., Swenson, W. G., Kunkler, P. E., White, D. M., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Monomeric+IgG+is+neuroprotective+via+enhancing+microglial+recycling+endocytosis+and+TNF-&#x03B1;lpha.">Monomeric IgG is neuroprotective via enhancing microglial recycling endocytosis and TNF-&#x03B1;lpha.</a> J Neurosci. 28 (47), 12199-12211 (2008).</li><li>Hailer, N. P., Jarhult, J. D., Nitsch, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Resting+microglial+cells+in+vitro:+analysis+of+morphology+and+adhesion+molecule+expression+in+organotypic+hippocampal+slice+cultures.">Resting microglial cells in vitro: analysis of morphology and adhesion molecule expression in organotypic hippocampal slice cultures.</a> Glia. 18 (4), 319-331 (1996).</li><li>Ransohoff, R. M., Perry, V. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microglial+physiology:+unique+stimuli,+specialized+responses.">Microglial physiology: unique stimuli, specialized responses.</a> Annu Rev Immunol. 27, 119-145 (2009).</li><li>Mitchell, H. M., White, D. M., Domowicz, M. S., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cold+pre-conditioning+neuroprotection+depends+on+TNF-&#x03B1;lpha+and+is+enhanced+by+blockade+of+interleukin-11.">Cold pre-conditioning neuroprotection depends on TNF-&#x03B1;lpha and is enhanced by blockade of interleukin-11.</a> J Neurochem DOI. , (2010).</li><li>Mitchell, H. M., White, D. M., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strategies+for+study+of+neuroprotection+from+cold-preconditioning.">Strategies for study of neuroprotection from cold-preconditioning.</a> J Vis Exp. (43), (2010).</li><li>Kunkler, P. E., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reactive+astrocytosis+from+excitotoxic+injury+in+hippocampal+organ+culture+parallels+that+seen+in+vivo.">Reactive astrocytosis from excitotoxic injury in hippocampal organ culture parallels that seen in vivo.</a> J Cereb Blood Flow Metab. 17 (1), 26-43 (1997).</li><li>Grinberg, Y. Y., Milton, J. G., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spreading+depression+sends+microglia+on+Lévy+flights.">Spreading depression sends microglia on Lévy flights.</a> PLoS ONE. 6 (4), (2011).</li><li>Koroleva, V. I., Oitzl, M. S., Bures, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Threshold+of+synaptically+elicited+cortical+spreading+depression:+drug-induced+changes+in+rats.">Threshold of synaptically elicited cortical spreading depression: drug-induced changes in rats.</a> Electroencephalogr Clin Neurophysiol. 60 (1), 55-64 (1985).</li><li>Gubern, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+of+housekeeping+genes+for+quantitative+real-time+PCR+in+in-vivo+and+in-vitro+models+of+cerebral+ischaemia.">Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemia.</a> BMC Mol Biol. 10, 57-57 (2009).</li><li>Tian, Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+quantification+of+ADAMTS+expression+in+an+animal+model+of+cerebral+ischemia+using+real-time+PCR.">The quantification of ADAMTS expression in an animal model of cerebral ischemia using real-time PCR.</a> Acta Anaesthesiol Scand. 51 (2), 158-164 (2007).</li><li>Pfaffl, M. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+mathematical+model+for+relative+quantification+in+real-time+RT-PCR.">A new mathematical model for relative quantification in real-time RT-PCR.</a> Nucleic Acids Res. 29 (9), e45-e45 (2001).</li><li>Bustin, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+MIQE+guidelines:+minimum+information+for+publication+of+quantitative+real-time+PCR+experiments.">The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments.</a> Clin Chem. 55 (4), 611-622 (2009).</li><li>Pusic, A. D., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammatory+gene+micro+array+profiling+demonstrates+"T-cell-like"+activation+after+recurrent+spreading+depression+-+implications+for+migraine+pathogenesis.">Inflammatory gene micro array profiling demonstrates "T-cell-like" activation after recurrent spreading depression - implications for migraine pathogenesis.</a> Soc Neurosci abst. , (2010).</li><li>Quinn, B., Graybiel, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+differentiated+silver+intensification+procedure+for+the+peroxidase-diaminobenzidine+reaction.">A differentiated silver intensification procedure for the peroxidase-diaminobenzidine reaction.</a> J Histochem Cytochem. 44 (1), 71-74 (1996).</li><li>Caggiano, A. O., Kraig, R. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Eicosanoids+and+nitric+oxide+influence+induction+of+reactive+gliosis+from+spreading+depression+in+microglia+but+not+astrocytes.">Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes.</a> J Comp Neurol. 369 (1), 93-108 (1996).</li></ol>

Нет конфликта интересов объявлены.

СД пароксизмальной возмущение мозга, характеристики которого хорошо сохранились и во всех видах и областях мозга изучить. SD широко изучается в коре головного мозга. Тем не менее, нейронные сложности схемы этой структуры (по сравнению с гиппокамп), а также неспособность держать неокортекса жив в пробирке с покоя иммунные функции в течение длительных периодов, сделать его менее полезным в подготовке пробирке для определения долгосрочных последствий восприимчивости SD. В отличие от этого, гиппокамп не только структуры мозга, который является наиболее чувствительным к SD, но и archicortical структуру с более упрощенной структуры нейронной цепи и функция, которая хорошо подходит для определения нейроиммунных помощью которых нейронная активность может модулировать SD восприимчивость .

modeling neural immune signaling of episodic and chronic migraine using spreading depression in vitro

Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options. We seek to define how neural immune signaling modulates the susceptibility to migraine, modeled in vitro using spreading depression (SD), as a means to develop novel therapeutic targets for episodic and chronic migraine. SD is the likely cause of migraine aura and migraine pain. It is a paroxysmal loss of neuronal function triggered by initially increased neuronal activity, which slowly propagates within susceptible brain regions. Normal brain function is exquisitely sensitive to, and relies on, coincident low-level immune signaling. Thus, neural immune signaling likely affects electrical activity of SD, and therefore migraine. Pain perception studies of SD in whole animals are fraught with difficulties, but whole animals are well suited to examine systems biology aspects of migraine since SD activates trigeminal nociceptive pathways. However, whole animal studies alone cannot be used to decipher the cellular and neural circuit mechanisms of SD. Instead, in vitro preparations where environmental conditions can be controlled are necessary. Here, it is important to recognize limitations of acute slices and distinct advantages of hippocampal slice cultures. Acute brain slices cannot reveal subtle changes in immune signaling since preparing the slices alone triggers: pro-inflammatory changes that last days, epileptiform behavior due to high levels of oxygen tension needed to vitalize the slices, and irreversible cell injury at anoxic slice centers. 
In contrast, we examine immune signaling in mature hippocampal slice cultures since the cultures closely parallel their in vivo counterpart with mature trisynaptic function; show quiescent astrocytes, microglia, and cytokine levels; and SD is easily induced in an unanesthetized preparation. Furthermore, the slices are long-lived and SD can be induced on consecutive days without injury, making this preparation the sole means to-date capable of modeling the neuroimmune consequences of chronic SD, and thus perhaps chronic migraine. We use electrophysiological techniques and non-invasive imaging to measure neuronal cell and circuit functions coincident with SD. Neural immune gene expression variables are measured with qPCR screening, qPCR arrays, and, importantly, use of cDNA preamplification for detection of ultra-low level targets such as interferon-gamma using whole, regional, or specific cell enhanced (via laser dissection microscopy) sampling. Cytokine cascade signaling is further assessed with multiplexed phosphoprotein related targets with gene expression and phosphoprotein changes confirmed via cell-specific immunostaining. Pharmacological and siRNA strategies are used to mimic and modulate SD immune signaling.

Watch this Scientific Journal Video about Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro at JoVE.com

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Мигрень и превращение его в хронической мигрени огромные нагрузки здравоохранения нуждаются в улучшении вариантов лечения. Мы стремимся, чтобы определить, как нейронные иммунной сигнализации модулирует чувствительность к мигрени, созданный по образцу<em&gt; В пробирке</em&gt; Использование распространяющейся депрессии в гиппокампе культур ломтик, как средства для разработки новых терапевтических целей.

Моделирование нейронных иммунной сигнализации эпизодической и хронической мигрени Использование распространяющейся депрессии In Vitro</em

Migraine and its transformation to chronic migraine are healthcare burdens in need of improved treatment options.  We seek to define how neural immune ...

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Neuroscience

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

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