TGHのNIH R21NS42516 TGHのクレイグHニールセン財団助成83860 NIDRR - RRTC。 CKTのAPTA博士奨学金

<ol>
	<li>Miller, J. F., Paul, K. D., Rymer, W. Z., Heckman, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=5-HT1B/1D+agonist+CGS-12066B+attenuates+clasp+knife+reflex+in+the+cat.">5-HT1B/1D agonist CGS-12066B attenuates clasp knife reflex in the cat.</a> J Neurophysiol. 74, 453-456 (1995).</li><li>Gimenez y Ribotta, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematic+analysis+of+recovered+locomotor+movements+of+the+hindlimbs+in+paraplegic+rats+transplanted+with+monoaminergic+embryonic+neurons.">Kinematic analysis of recovered locomotor movements of the hindlimbs in paraplegic rats transplanted with monoaminergic embryonic neurons.</a> Ann N Y Acad Sci. 860, 521-523 (1998).</li><li>Landry, E. S., Guertin, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+5-HT1+and+5-HT2+receptor+agonists+on+hindlimb+movements+in+paraplegic+mice.">Differential effects of 5-HT1 and 5-HT2 receptor agonists on hindlimb movements in paraplegic mice.</a> Prog Neuropsychopharmacol Biol Psychiatry. 28, 1053-1060 (2004).</li><li>Liu, J., Jordan, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stimulation+of+the+parapyramidal+region+of+the+neonatal+rat+brain+stem+produces+locomotor-like+activity+involving+spinal+5-HT7+and+5-HT2A+receptors.">Stimulation of the parapyramidal region of the neonatal rat brain stem produces locomotor-like activity involving spinal 5-HT7 and 5-HT2A receptors.</a> J Neurophysiol. 94, 1392-1404 (2005).</li><li>Fong, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+cord-transected+mice+learn+to+step+in+response+to+quipazine+treatment+and+robotic+training.">Spinal cord-transected mice learn to step in response to quipazine treatment and robotic training.</a> J Neurosci. 25, 11738-11747 (2005).</li><li>Murray, K., Nakae, A., Stephens, M. J., Rank, M., D Amico, J., Harvey, P., Li, X., Harris, L., Ballou, E. W., Anelli, R., Heckman, C. J., Mashimo, T., Vavrek, R., Sanelli, L., Gorassini, M. A., Bennett, D. J., Fouad, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+motoneuron+and+locomotor+function+after+chronic+spinal+cord+injury+depends+on+constitutive+activity+in+5-HT2C+receptors.">Recovery of motoneuron and locomotor function after chronic spinal cord injury depends on constitutive activity in 5-HT2C receptors.</a> Nature Medicine. , (2010).</li><li>Pariente, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoxetine+modulates+motor+performance+and+cerebral+activation+of+patients+recovering+from+stroke.">Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke.</a> Ann Neurol. 50, 718-729 (2001).</li><li>Hornby, T. G., Lewek, M. D., Thompson, C. K., Heitz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeated+maximal+volitional+effort+contractions+in+human+spinal+cord+injury:+initial+torque+increases+and+reduced+fatigue.">Repeated maximal volitional effort contractions in human spinal cord injury: initial torque increases and reduced fatigue.</a> Neurorehabil Neural Repair. 23, 928-938 (2009).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> ACSM's Guidelines for Exercise Testing and Prescription. , (2000).</li><li>Lewek, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Allowing+intralimb+kinematic+variability+during+locomotor+training+poststroke+improves+kinematic+consistency:+a+subgroup+analysis+from+a+randomized+clinical+trial.">Allowing intralimb kinematic variability during locomotor training poststroke improves kinematic consistency: a subgroup analysis from a randomized clinical trial.</a> Phys Ther. 89, 829-839 (2009).</li><li>Fung, J., Barbeau, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dynamic+EMG+profile+index+to+quantify+muscular+activation+disorder+in+spastic+paretic+gait.">A dynamic EMG profile index to quantify muscular activation disorder in spastic paretic gait.</a> Electroencephalogr Clin Neurophysiol. 73, 233-244 (1989).</li><li>Bohannon, R. W., Smith, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrater+reliability+of+a+modified+Ashworth+scale+of+muscle+spasticity.">Interrater reliability of a modified Ashworth scale of muscle spasticity.</a> Phys Ther. 67, 206-207 (1987).</li><li>Benz, E., TG, H. o. r. n. b. y., RK, B. o. d. e., Scheidt, R. A., Schmit, B. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+physiologically+based+clinical+measure+for+spastic+reflexes+in+spinal+cord+injury.">A physiologically based clinical measure for spastic reflexes in spinal cord injury.</a> Arch Phys Med Rehabil. 86, 52-59 (2005).</li></ol>

利害の衝突は宣言されません。

このビデオデモでは、反射活動の変化、人間のSCIのSSRIの急性経口投与後の意志の強さと歩行を評価するための方法を強調しています。アセスメントのこのバッテリーは、SSRIの急性経口投与後、いわゆる異常な反射活動の増加にもかかわらず、SCIと個々の運動能力のわずかな変化で、意志の強さの改善を示したことを示している。これらの個体では拡張の痙性の影響は、歩行機能に有害表示されません。また、歩行能力の改善は、急性病変を有する患者においてより顕著かもしれません。継続的な研究では、SCIの動物モデルで採用されているように、複合SSRIと集中的な物理的な介入の有効性を判断するためにこれらの同じような定量的および臨床的評価を使用してください。長年、比較的新しい基礎科学の研究に基づいて、健全な理論的枠組みと、これらの方法は臨床人口に翻訳などの情報を得ることができますし、SCIを持つ個人の機能回復を強化するために臨床現場で使用されている伝統的なプロトコルのいくつかを忌避することができる。

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<td>Isokinetic Dynamometer</td>
<td>&nbsp;</td>
<td>Biodex</td>
<td>System 3 with Rehab Toolkit</td>
<td>&nbsp;</td>
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<td>EMG system</td>
<td>&nbsp;</td>
<td>Delysis</td>
<td>Bagnoli 2.1</td>
<td>&nbsp;</td>
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<td>EMG system</td>
<td>&nbsp;</td>
<td>Noraxon</td>
<td>Mayosystem 1400a</td>
<td>&nbsp;</td>
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<td>Metabolic</td>
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<td>&nbsp;</td>
<td>Bertec</td>
<td>FIT</td>
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methods to quantify pharmacologically induced alterations in motor function in human incomplete sci

脊髄損傷（SCI）は随意運動の制御に深遠な赤字を生成する消耗性疾患、である。医療安定化に続いて、SCIからの回復は通常、長期的なリハビリテーションを行います。歩行能力の回復は受傷後早期に多くの患者の主要な目標ですが、モーター不完全なSCI患者は、意志のコントロールの部分的な保存を示す、この目標を達成するために必要な十分な残留降順経路を持つことができます。しかし、物理的な介入にもかかわらず、脱力感、および痙攣や痙攣と呼ばれる異常な不随意の反射活動の現れ、を含む運動障害は、軽減歩行の回復に寄与すると考えられる。空論の思想は、SCIに関連付けられているこの異常な運動反射の改善は、患者への機能的なメリットを生み出すことを示唆している。これらの戦略は、歩行能力を改善することを示唆少し実証的データがあるように続けるが、例えば、医師やセラピストが、痙性や痙攣を減少させるに向け、特定の薬理学的または物理的な介入を提供します。 過去数十年の間に、データの蓄積は、セロトニン（5HT）とノルエピネフリン（NE）を含むモノアミンのアクションを、模倣したり容易にするエージェントを含む特定の神経調節剤は、SCIの動物モデルでの歩行動作を開始または拡張できることを示唆している。興味深いことに、5HTergicアゴニスト、特に、これらの薬剤の多くは、顕著に順番にもこれらの動物における反射活動を増加させる脊髄の興奮性を、高めることができます。基本的な科学実験からヒトのSCI、実証的証拠を、以下の回復の伝統的な理論の直感に反するが運動行動のこの反射超興奮性と世代が神経調節入力（5HT）で並列に駆動され、SCI、以下の機能回復のために必要であることを示唆している。 調査結果の直接の翻訳は非常に困難になることができますが、人間のSCI後の回復を促進するための基本的な科学的研究から派生したこの新しい概念のアプリケーションは、シームレスに見えるかもしれません。特に、動物モデルにおいて、移植されたカテーテルは、直接脊髄の回路上に非常に特定の5HTアゴニスト化合物の送達を容易にします。この技術の人間への変換は、人間の臨床試験のために安全かつ有効である5HT受容体サブタイプに向け、特定の手術手技や使用可能な薬理学的作用物質の不足によって妨げられている。しかし、そのような選択的セロトニン再取り込み阻害薬（SSRI）として一般に入手可能な5HTergic剤の経口投与は、ヒトの歩行の回復を容易にするために中央の5HT濃度を高めるために実行可能な選択肢かもしれません。これらのSSRIは強さ、反射、および歩行能力の回復上の特定の焦点を当てて、SCIに続く人間の運動行動を調節する方法の体系的な定量化は、欠落している。 このビデオデモでは、体系的かつ定量的に反射活動の変調、人間のSCIのSSRIの急性経口投与後の意志の強さと歩行を評価するために進歩的な試みです。エージェントは、集中的な物理的な介入と組み合わせて繰り返し薬剤投与を含む長期的な研究で、この患者集団で運動機能に直接的な影響を評価するために、単一の日に適用されます。

Watch this Scientific Journal Video about Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI at JoVE.com

Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

このビデオでは、セロトニン再取り込み阻害剤（SSRI）の急性経口投与の結果として、モータ不完全なSCIを持つ個人の臨床および定量的評価を通じて、意志の強さと歩行、反射活動の変調を示しています。

人間の不完全なSCIにおける運動機能の薬理学的に誘起される変化を定量化する方法

Spinal cord injury (SCI) is a debilitating disorder, which produces profound deficits in volitional motor control. Following medical stabilization, ...

methods-to-quantify-pharmacologically-induced-alterations-motor

Research

JoVE Journal

Medicine

13.7K ビュー.  Rehabilitation Institute of Chicago. このビデオでは、セロトニン再取り込み阻害剤（SSRI）の急性経口投与の結果として、モータ不完全なSCIを持つ個人の臨床および定量的評価を通じて、意志の強さと歩行、反射活動の変調を示しています。

ビデオ: Methods to Quantify Pharmacologically Induced Alterations in Motor Function in Human Incomplete SCI

Technique to Collect Fungiform (Taste) Papillae from Human Tongue

The sense of taste is critical for human life. It informs the body about the quality of food that will be potentially ingested and stimulates metabolic processes that prepare the alimentary canal for digestion. Steady progress is being made towards understanding the early biochemical and molecular events underlying taste transduction (for a review, Breslin and Spector, 20081). However, progress to date has largely resulted from animal models. Yet, since marked differences in receptor specificity and receptor density vary among species, human taste transduction will only be understood by using human taste tissue. Here we describe a biopsy technique to collect human fungiform papillae, visible as rounded pink anterior structures, about 0.5 mm in diameter that contain taste buds. These biopsied papillae are used for several purposes including the isolation of viable taste bud cells, in situ hybridization, immunohistochemistry and, through techniques of molecular biology, the identification of taste-specific novel proteins.

Technique to Collect Fungiform Taste Papillae from Human Tongue

Knowledge of molecular mechanisms underlying gustatory transduction has recently enjoyed significant advances, largely due to using animal models. However, the wide diversity in taste sensitivity and specificity among mammals warrants studies in human tissue. We describe a biopsy technique to collect living taste cells from the papillae on human tongue.

人間の舌から茸（味）乳頭を収集する手法

The sense of taste is critical for human life. It informs the body about the quality of food that will be potentially ingested and stimulates metabolic ...

医学

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness1 and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them2. This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia3. The male-to-female ratio of mutation rate is estimated at about 4&#x2013;6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males4. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.

Molecular genetic strategy for finding de novo mutations causing common disorders such as autism and schizophrenia.

そのような自閉症や統合失調症のような一般的な疾患でのde novo変異を同定するための戦略

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

In Vivo Canine Muscle Function Assay

We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric 
contractions. The pelvic limb of an anesthetized dog is immobilized in a stereotactic frame to align the tibia at a right angle to the femur. Adhesive wrap affixes the 
paw to a pedal mounted on the shaft of a servomotor to measure torque. Percutaneous nerve stimulation activates pelvic limb muscles of the paw to either push (extend) or 
pull (flex) against the pedal to generate isometric torque. Percutaneous tibial nerve stimulation activates tibiotarsal extensor muscles. Repeated eccentric (lengthening) 
contractions are induced in the tibiotarsal flexor muscles by percutaneous peroneal nerve stimulation. The eccentric protocol consists of an initial isometric contraction 
followed by a forced stretch imposed by the servomotor. The rotation effectively lengthens the muscle while it contracts, e.g., an eccentric contraction. During 
stimulation flexor muscles are subjected to an 800 msec isometric and 200 msec eccentric contraction. This procedure is repeated every 5 sec. To avoid fatigue, 4 min rest 
follows every 10 contractions with a total of 30 contractions performed.

In Vivo Canine Muscle Function Assay

We describe a minimally-invasive and painless method to measure canine hindlimb muscle strength and muscle response to repeated eccentric contractions.

ビボ犬筋肉の機能アッセイに

We describe a minimally-invasive and reproducible method to measure canine pelvic limb muscle strength and muscle response to repeated eccentric 
...

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily obtained electrocardiogram (ECG) are established, well-validated prognostic indicators of cardiac risk in patients suffering 
from a number of cardiomyopathies. Increased heart rate, decreased heart rate variability (HRV), and increased duration and variability of cardiac 
ventricular electrical activity (QT interval) are all indicative of enhanced cardiac risk 1-4. In animal models, it is valuable to compare 
these ECG-derived variables and susceptibility to experimentally induced arrhythmias. Intravenous infusion of the arrhythmogenic agent aconitine has
 been widely used to evaluate susceptibility to arrhythmias in a range of experimental conditions, including animal models of depression 5 and 
 hypertension 6, following exercise 7 and exposure to air pollutants 8, as well as determination of the antiarrhythmic efficacy of pharmacological 
 agents 9,10. 
It should be noted that QT dispersion in humans is a measure of QT interval variation across the full set of leads from a 
standard 12-lead ECG. Consequently, the measure of QT dispersion from the 2-lead ECG in the rat described in this protocol is different than that 
calculated from human ECG records. This represents a limitation in the translation of the data obtained from rodents to human clinical medicine.
Status epilepticus (SE) is a single seizure or series of continuously recurring seizures lasting more than 30 min 
11,12 11,12, and results in mortality in 20% of cases 13. Many individuals survive the SE, but die within 30 days 14,15.
 The mechanism(s) of this delayed mortality is not fully understood. It has been suggested that lethal ventricular arrhythmias contribute to many of these 
 deaths 14-17. In addition to SE, patients experiencing spontaneously recurring seizures, i.e. epilepsy, are at risk of premature 
 sudden and unexpected death associated with epilepsy (SUDEP) 18. As with SE, the precise mechanisms mediating SUDEP are not known. 
 It has been proposed that ventricular abnormalities and resulting arrhythmias make a significant contribution 18-22.
 To investigate the mechanisms of seizure-related cardiac death, and the efficacy of cardioprotective therapies, it is 
 necessary to obtain both ECG-derived indicators of risk and evaluate susceptibility to cardiac arrhythmias in animal models of seizure disorders 
 23-25. Here we describe methods for implanting ECG electrodes in the Sprague-Dawley laboratory rat (Rattus norvegicus), following SE,
 collection and analysis of ECG recordings, and induction of arrhythmias during iv infusion of aconitine.
 These procedures can be used to directly determine the relationships between ECG-derived measures of cardiac electrical 
 activity and susceptibility to ventricular arrhythmias in rat models of seizure disorders, or any pathology associated with increased risk of sudden 
 cardiac death.

Techniques for measurement of electrical activity of the heart by electrocardiogram (ECG), and analysis of cardiac risk factors and susceptibility to arrhythmias following status epilepticus (SE) in the rat are described.

心電図心臓のリスクの指標の評価、およびてんかん重積状態後のラットにおけるアコニチン誘発性不整脈に対する感受性のための方法

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily ...

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients.
In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS.

Object From Motion (OFM) and Time-constrained stereo protocols are sensitive tools to identify monocular and binocular dynamic visual function deficits, which are uniquely affected in optic neuritis patients. Furthermore, these tests may be used as quantitative noninvasive tools to assess the extent of myelination along visual pathways.

視神経炎患者における脱髄次のVisual損傷と修復を特定し、定量化するために、動的なビジュアルテスト

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to ...

Multi-electrode Array Recordings of Human Epileptic Postoperative Cortical Tissue

Epilepsy, affecting about 1% of the population, comprises a group of neurological disorders characterized by the periodic occurrence of seizures, which disrupt normal brain function. Despite treatment with currently available antiepileptic drugs targeting neuronal functions, one third of patients with epilepsy are pharmacoresistant. In this condition, surgical resection of the brain area generating seizures remains the only alternative treatment. Studying human epileptic tissues has contributed to understand new epileptogenic mechanisms during the last 10 years. Indeed, these tissues generate spontaneous interictal epileptic discharges as well as pharmacologically-induced ictal events which can be recorded with classical electrophysiology techniques. Remarkably, multi-electrode arrays (MEAs), which are microfabricated devices embedding an array of spatially arranged microelectrodes, provide the unique opportunity to simultaneously stimulate and record field potentials, as well as action potentials of multiple neurons from different areas of the tissue. Thus MEAs recordings offer an excellent approach to study the spatio-temporal patterns of spontaneous interictal and evoked seizure-like events and the mechanisms underlying seizure onset and propagation. Here we describe how to prepare human cortical slices from surgically resected tissue and to record with MEAs interictal and ictal-like events ex vivo.

We here describe how to perform multi-electrode array recordings of human epileptic cortical tissue. Epileptic tissue resection, slice preparation and multi-electrode array recordings of interictal and ictal events are demonstrated in detail.

人間のてんかん術後皮質組織の多電極アレイ録音

Epilepsy, affecting about 1% of the population, comprises a group of neurological disorders characterized by the periodic occurrence of seizures, which ...

Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physiology. Elimination of one or more of these components will have a detrimental impact on the study results. Moreover, the energy level capability of the fluoroscopy system will determine which swallow parameters can be investigated. Most research centers have high energy fluoroscopes designed for use with people and larger animals, which results in exceptionally poor image quality when testing mice and other small rodents. Despite this limitation, we have identified seven VFSS parameters that are consistently quantifiable in mice when using a high energy fluoroscope in combination with the new murine VFSS protocol. We recently obtained a low energy fluoroscopy system with exceptionally high imaging resolution and magnification capabilities that was designed for use with mice and other small rodents. Preliminary work using this new system, in combination with the new murine VFSS protocol, has identified 13 swallow parameters that are consistently quantifiable in mice, which is nearly double the number obtained using conventional (i.e., high energy) fluoroscopes. Identification of additional swallow parameters is expected as we optimize the capabilities of this new system. Results thus far demonstrate the utility of using a low energy fluoroscopy system to detect and quantify subtle changes in swallow physiology that may otherwise be overlooked when using high energy fluoroscopes to investigate murine disease models.

This study successfully adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research.

マウス疾患モデルで嚥下障害を検出し、特徴づけるために、人間のVideofluoroscopicツバメ調査方法を適応させる

This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating ...

Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial &#34;Treatment with L-citrulline and metformin in Duchenne muscular dystrophy&#34;. The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). The test shows high intra- and inter-rater variability but only when strictly following guidelines of the materials, examination steps, and calculation of scores. The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration. Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability.

The aim of this study is to present the most reliable clinical outcome measures and their correlations with quantitative muscle MRI in ambulant patients with Duchenne muscular dystrophy.

運動機能、デュシェンヌ型筋ジストロフィー児の外来の他の臨床パラメーターの測定

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most ...

Using a Chemical Biopsy for Graft Quality Assessment

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated with an increased survival rate and greater quality of patient&#8217;s life when compared to conventional dialysis. Regrettably, transplantology suffers from a lack of reliable methods for organ quality assessment. Standard diagnostic techniques are limited to macroscopic appearance inspection or invasive tissue biopsy, which do not provide comprehensive information about the graft. The proposed protocol aims to introduce solid phase microextraction (SPME) as an ideal analytical method for comprehensive metabolomics and lipidomic analysis of all low molecular compounds present in kidneys allocated for transplantation. The small size of the SPME probe enables performance of a chemical biopsy, which enables extraction of metabolites directly from the organ without any tissue collection. The minimum invasiveness of the method permits execution of multiple analyses over time: directly after organ harvesting, during its preservation, and immediately after revascularization at the recipient&#8217;s body. It is hypothesized that the combination of this novel sampling method with a high-resolution mass spectrometer will allow for discrimination of a set of characteristic compounds that could serve as biological markers of graft quality and indicators of possible development of organ dysfunction.

The protocol presents utilization of the chemical biopsy approach followed by comprehensive metabolomic and lipidomic analysis for quality assessment of kidney grafts allocated for transplantation.

移植質評価のための化学バイオプシーの使用

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated ...

A Non-Invasive Method for Generating the Cyclic Loading-Induced Intra-Articular Cartilage Lesion Model of the Rat Knee

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely correlated with a history of articular cartilage damage and ligament avulsion. Surgical animal models of OA of the knee play an important role in understanding the onset and progression of post-traumatic OA and aid in the development of novel therapies for this disease. However, non-surgical models have been recently considered to avoid traumatic inflammation that could affect the evaluation of the intervention. 
In this study, an intra-articular cartilage lesion rat model induced by in vivo cyclic compressive loading was developed, which allowed researchers to (1) determine the optimal magnitude, speed, and duration of load that could cause focal cartilage damage; (2) assess post-traumatic spatiotemporal pathological changes in chondrocyte vitality; and (3) evaluate the histological expression of destructive or protective molecules that are involved in the adaptation and repair mechanisms against joint compressive loads. This report describes the experimental protocol for this novel cartilage lesion in a rat model.

Here, we present the cyclic loading-induced intra-articular cartilage lesion model of the rat knee, generated by 60 cyclic compressions over 20 N, resulting in damage to the femoral condylar cartilage in rats.

ラット膝の周期的負荷誘発関節内軟骨病変モデルを生成するための非侵襲的方法

The pathophysiology of primary osteoarthritis (OA) remains unclear. However, a specific subclassification of OA in relatively younger age groups is likely ...