This work was supported by Interdisziplin&#228;res Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany (project N-215).

Hayvan deneyleri hayvan koruma kuralları ve Avrupa Toplulukları Konseyi yönergelerine (: 55,2-2531,01 76/11 onay numarası) uyarınca Wuerzburg Üniversitesi ve Aşağı Franken yasal devlet yetkilileri tarafından kabul edildi. Tüm çabalar kullanılan hayvanların ağrı veya rahatsızlık en aza indirmek için yapılmıştır. Not: Başka bir yerde 18 açıklandığı gibi Elektrot implantasyonu yapıldı. 1. Silindir Testi (Şekil 2) <ol><li> Bir% 0.1 asetik asit solüsyonu ile silindir temizleme şeffaf bir plastik cam bir silindir (19 cm: 40 cm, çap yükseklik) hazırlayın. </li><li> Deneyin tarih ve her sıçan kimlik numarası ile kartları hazırlayın. </li><li> Silindirin arkasındaki 90 ° açı iki ayna yerleştirin. </li><li> Kamera ve silindir arasındaki mesafe pençeleri iyi bir görünüm veriyor şekilde silindirin önünde kamerayı yerleştirin. </li><li> taşıma kutusunda sıçan yerleştirin. Not: Hayvanlar stresi önlemek için test öncesi deneyci tarafından ele alınmalıdır. </li><li> taşıma kutusunu kullanarak silindire ev kafes sıçan taşıyın. </li><li> Silindir (Şekil 3) sıçan yerleştirin. <ol><li> Her zaman faaliyette sirkadiyen farklılıkları önlemek için günün aynı anda tüm davranışsal testler. hayvan kablo ile uyaran jeneratör bağlıysa kablo deney sırasında bükülmüş olmadığından emin olun. </li></ol></li><li> kamerada &quot;kayıt&quot; düğmesine basın. Deney ve kameraya sıçan kimlik numarası gerçek tarih ile kart göster. Kayda başla. </li><li> Beş dakika sonra, silindir hayvan kaldırmak ve taşıma kutusunu kullanarak ev kafes içine geri koymak. </li><li> Bir% 0.1 asetik asit solüsyonu ile silindirini. </li><li> Sağ ve sol pençe duvar kişileri (yüzde pençe kullanımı) yanı sıra r sayarak kaydedilen videodan pençe kullanımının değerlendirilmesiküpe (veya silindir duvarına destek olmadan arka pençeleri üzerinde duran). silindir testi aynı zamanda bir uygun yazılım tarafından otomatik olarak değerlendirilebilir. Not: Sağlıklı bir sıçan eşit iki patilerini kullanır. hemiparkinsonian sıçan daha az ölçüde bir lezyon nedeniyle etkilenen pençe kullanır. </li></ol> 2. Merdiven Testi (Şekil 4) <ol><li> Toplama Aşaması <ol><li> antrenman öncesinde bir gün merdiven testte kullanılan pelet hayvanları tanımak. <ol><li> İsteğe bağlı: hayvanın motivasyon (ücretsiz beslenme seviyesinin 16% 90 vücut ağırlığını korumak için standart laboratuvar chow 10-15 g) bir diyet kısıtlaması kullanmak artırmak için. Ancak, bu olumlu bir eğitim etkiyi elde etmek zorunlu değildir. Bu çalışma, gıda kısıtlama olmaksızın yapılmıştır. </li></ol></li><li> Bir şeffaf plastik cam merdiven kutu hazırlayın (yükseklik: 34.5 cm, uzunluk: 35.5 cm, genişlik: 12 cm ve dar bölme 6 cm)% 0.1 ac kutuyu temizleyerekasetik asit çözeltisi. Not: merdiven kutusu yükseltilmiş platform ve dar bölmesinde iki merdiven ile bir iki bölmeli-kutusudur. dar bölmesindeki merdivenlerde sol adımlar, sadece sol pençe sadece sağ pençe ile doğru adımlar ulaşılabilir. Not: kapaksız yüksek kutusuna, kablo ile uyarılmış sıçan deneyleri için kullanılacak ise, standart bir merdiven kutuları, bir kapak ile iki bölme oluşur. </li><li> merdiven çıkarın ve sekiz 45 mg pelet her adımda kuyu doldurun. </li><li> merdiven yerleştirin ve artan platformda sekiz ek pelet koydu. </li><li> taşıma kutusunda sıçan yerleştirin. </li><li> taşıma kutusunu kullanarak merdiven kutusuna ev kafes sıçan taşıyın. </li><li> Merdiven kutusuna siçana (Şekil 5) yerleştirin. </li><li> Beş dakika sonra, merdiven kutusundan hayvan kaldırmak ve taşıma kutusunu kullanarak ev kafes içine geri koymak. </li><li> kaç Notpelet sağ ve sol merdiven platformu ve (sonunda) den yemiş bulundu. </li><li> Sekiz 45 mg pelet her adımda kuyu doldurarak merdiven doldurun. </li><li> Bir% 0.1 asetik asit solüsyonu ile merdiven kutusu temiz ve platform ek granül yerleştirin. </li><li> Bu yordamı (satın alma aşaması) üst üste üç gün tekrarlayın. Not: erkek Sprague Dawley fareleri üzerinde gerçekleştirilmiştir tarif edilen tüm deneyler. Farklı eğitim modülleri süresi farklı suşu, cinsiyet ve işportacı ve sıçanlarda farklı olabilir. </li></ol></li><li> Özgür Seçim Testi <ol><li> Bir% 0.1 asetik asit solüsyonu ile merdiven kutusu temizleyin. </li><li> merdiven çıkarın ve sekiz 45 mg pelet her adımda kuyu doldurun. </li><li> taşıma kutusunda sıçan yerleştirin. </li><li> taşıma kutusunu kullanarak merdiven kutusuna ev kafes sıçan taşıyın. </li><li> merdiven kutusunda sıçan yerleştirin. </li><li> Beş dakika sonra, merdiven hayvan kaldırmakvaka kutusu ve taşıma kutusunu kullanarak ev kafes içine geri koymak. sağ ve sol merdivenden yemiş kaç topaklar unutmayın. </li><li> Not: Hayvanlar hala pelet açgözlü ile ilgili sorunlar varsa, onlar kolayca ulaşılabilir platformda biraz daha ekleyin. </li><li> Sekiz 45 mg pelet her adımda kuyu doldurarak merdiven doldurun. </li><li> Bir sonraki bir hayvan için% 0.1 asetik asit solüsyonu ile merdiven kutusu temizleyin. </li><li> Bu yordamı (özgür seçim aşaması) üst üste üç gün tekrarlayın. Not: sunulan sonuçlar modüller arasında bir dinlenme süresi olmadan yapılan eğitim ile elde edilmiştir. Bazı gruplar eğitim sürecini desteklemek için, konsolidasyon için bir dinlenme günü tercih ederim. </li></ol></li><li> Zorla Seçmeli Test <ol><li> Bir% 0.1 asetik asit solüsyonu ile merdiven kutusu temizleyin. </li><li> merdiven çıkarın ve sekiz (modülün ilk üç gün) ya da dört (ardışık thr sol merdiven her adım kuyu doldurmakmodülü) 45 mg pelet EE gün. <ol><li> değer düşüklüğü meydana gelecektir tarafında, zorunlu seçim testi yapın. Not: sağ hemisfer üzerinde Parkinson lezyonu yapmak ve bu nedenle seçici sol pençe tren. </li></ol></li><li> taşıma kutusunda sıçan yerleştirin. </li><li> taşıma kutusunu kullanarak merdiven kutusuna ev kafes sıçan taşıyın. </li><li> merdiven kutusunda sıçan yerleştirin. </li><li> Beş dakika sonra, merdiven kutusundan hayvan kaldırmak ve taşıma kutusunu kullanarak ev kafes içine geri koymak. </li><li> Sol merdiven yemiş kaç topaklar unutmayın. </li><li> Sekiz ya da dört 45 mg pelet (pelet sayısı eğitim gününde bağlıdır) her adımda kuyu doldurarak merdiven doldurun. </li><li> Bir sonraki bir hayvan için% 0.1 asetik asit solüsyonu ile merdiven kutusu temizleyin. </li><li> Bu yordamı (zorunlu seçim aşaması) üst üste altı gün tekrarlayın. </li></ol></li><li> Veri toplama <ol> &lt;İki gün üst üste (sol merdiven de her dört pelet) zorunlu seçim modülü için tarif edildiği gibi li&gt; deney yapın. İki gün ortalama olarak başarı oranını (yemiş pelet sayısı) hesaplayın. </li></ol></li></ol>

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The authors declare that they have no competing financial interests.

Bu makalede, silindir ve merdiven testi için ayrıntılı bir eğitim protokolü açıklanır. İkincisi nedeniyle vasıflı sıçanlarda 16,17 ulaşan karmaşık kavrama davranış ve ince motor hareketlerini değerlendirmek için tasarlanmıştır. sonuç ölçümü objektif bir ölçümü olan test boyunca yemiş pelet sayısı olarak ifade edilir. Protokol, Parkinson hastalığı ve diğer motor hastalığı modellerinde sıçan modellerinde kullanılabilir. silindir testi sıçanlarda pençe kullanımı...

Subtalamik çekirdek (STN) Derin beyin stimülasyonu Parkinson hastalığı 1 ve diğer hareket bozukluklarının için etkili bir tedavi seçeneğidir. Altta yatan mekanizmalar hala tam olarak anlaşılamamıştır ve çok faktörlü, ama önemli bir özelliği uyarıcı elektrot 2-4 civarında akson tekrarlayan depolarizasyon nöronal ağ etkinliğinin modülasyonu olduğunu vardır. Yüksek frekanslı (&gt; 100 Hz) stimülasyonu beyin hedefleri ve DBS belirtiler için yararlı bir etki için gereklidir. stimülasyon hacmi kapsadığı ve diğer liflerin, yanlışlıkla koaktivasyonuna derin beyin stimülasyonu sonucu yan etkileri gibi piramidal yolu olarak farklı işlevler, işine yaramak. Bu nedenle, yan etki elemanları 5,6 Koaktivasyon kaçınarak, tercihen faydalı bir nöral elemanlar aktive uyarım parametrelerinin geliştirilmesi istenebilecektir. neurophysiology örneğin ince Modifiye sunabilir rağmenprogramlama stratejileri öncelikle oldukça nörofizyolojik fikir kullanmak yerine, piyasada mevcut DBS cihazların sınırlı programlama seçenekleri ile hastaların &quot;deneme-yanılma&quot; ile değerlendirilen ve kısıtlı olmasından dolayı DBS ng seçenekleri, bilimsel ilerleme, son yirmi yılda en az olmuştur ve sistematik tam parametre alanı keşfetmek için deneysel ayarları tanımlı. Biz önce klinik keşif Parkinsonizmin kemirgen modellerinde alternatif uyarım parametrelerini ekrana bir protokol öneriyoruz DBS araştırma translasyonel barikat aşmak için. Sıçanlarda tek taraflı Parkinson hastalığı sağ medial ön beyin demeti 7,8 içine 6-hidroksidopamin enjeksiyonları kullanılarak modellenmiştir. Elde edilen lezyon, hemiparkinsonian olarak ayrıca tarif, tirozin hidroksilaz immunohist düşük doz apomorfin enjeksiyonundan sonra rotasyon puanı değerlendirilmesi ile apomorfin testinde değerlendirilir ve onaylanır ölüm sonrasıochemistry. Düşük mortalite ve morbidite taşırken yöntemi uygulamak kolay ve son derece tekrarlanabilir. Elde edilen motorlu açıkları 7,8 çok ayrık; hayvanlar kendiliğinden keşif ve karmaşık kavrama hem davranış 9,10 sırasında karşı taraftaki sol pençe hafif bir bozulma gösterirler. Motor performansında hızlı ve güvenilir bir değişim ölçüm izin ve farklı nörostimülasyon ayarları ile zamanla tekrar edilebilir testler gereklidir derin beyin stimülasyonu protokollerinin etkinliğini değerlendirmek için. Çeşitli gruplar son derece değişken ve tutarsız sonuçlar 11-14 sıçanlarda 11 motor fonksiyonlarını değerlendirmek için farklı stimülasyon yaklaşımları ve farklı testler önerdi. Bu geçerlilik ve tamamlayıcılık predict yüksek olan testlerin bir dizi seçmek için bizi zorladı. Ayrıca, derin beyin stimülasyonu koşullarında motorun sonuçlarının değerlendirilmesi için, testler ani tarafından icra edilebilecek olan tercih edildimals uyaran jeneratör kablo ile bağlı. Bu amaçla biz pençe kullanım asimetri için bir test ve yetenekli ulaşmak için bir test oluşan test pili kurdu. Çalışmanın tasarımı, Şekil 1 &#39;de gösterilmiştir. Spontan pençe kullanım için biz dikey keşif sırasında pençe kullanım için yaygın olarak kullanılan bir testtir Shallert 15, tarif silindir testi uygulandı. hayvan Hiçbir eğitim gereklidir. Daha karmaşık kavrama davranışının değerlendirilmesi için biz Montoya 16 göre merdiven testi kurdu. Bizim protokol KLOTH 17&#39;ye göre modifiye edilir. fareler test kutusundan pelet ulaşmada on iki gün süre ile yetiştirilmektedir. eğitimden sonra deney yemiş pelet sayısı olarak tarif edilen bir başarı oranı sayarak karmaşık kavrama davranışı ölçülmesi için tatbik edilebilir. makale beh merdiven kutusunda detaylı eğitimi yanı sıra hem performansını sunarnaif, hemiparkinsonian ve derin beyin stimülasyonu koşullarında avioral testler.

<table><tbody><tr><td>Staircase box without lid</td><td>Glas Keil, Germany</td><td></td><td>custom made</td></tr><tr><td>Cylinder box</td><td>Glas Keil, Germany</td><td></td><td>custom made</td></tr><tr><td>Dustless precision pellets, 45 mg</td><td>Bio Serv</td><td>F0021</td><td></td></tr></tbody></table>

a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test

subtalamik nükleus derin beyin stimülasyonu Parkinson hastalığı için etkili bir tedavi seçeneğidir. Laboratuvarda biz hemiparkinsonian (tek taraflı lezyonlu) sıçanlarda farklı nörostimülasyon desenleri ekrana bir protokol kurdu. Kablo bağlı harici nörostimülasyon 24 saat süreleri sonunda motorlu sonuçları, sağ medial ön beyin demeti içine 6-hidroksidopamin (6-OHDA) enjekte subtalamik çekirdek içine kronik stimülasyon elektrotlar implante ve değerlendirerek tek taraflı Parkinson lezyon oluşturma oluşur . stimülasyon sabit akım uyarımı ile gerçekleştirilmiştir. genlik yan etkileri bireysel eşiğin altına% 20 kuruldu. Motor sonuç değerlendirme Shallert ve Montoya göre merdiven testinde ulaşan yetenekli değerlendirilmesi ile uygun silindir testi spontan pençe kullanımının değerlendirilmesi yapıldı. Bu protokol detaylı merdiven kutusuna eğitim açıklanır, cylinder testi, hem de hemiparkinsonian sıçanlarda hem de kullanımı. merdiven testi ince motor beceri düşüklüğü için daha duyarlı gibi görünüyor ve nörostimülasyon sırasında değiştirmek için daha fazla hassasiyet sergileyen çünkü her iki testin kullanımı gereklidir. tek taraflı Parkinson modeli ve iki davranış testleri kombinasyonu standart bir şekilde farklı stimülasyon parametreleri değerlendirilmesine olanak sağlamaktadır.

Bütün hayvanlar dopaminerjik lezyon ve elektrot konumu hem de bir post mortem histolojik doğrulama yapıldı. STN içinde doğru elektrot yerleştirme (Şekil 6) ve tam dopaminerjik lezyon (&gt; substantia nigra dopaminerjik nöronların% 90 kaybı) ile sadece hayvanların sonuç bölümünde (Şekil 7) içine alındı. lezyonlu koşul altında gerçekleştirilen silindir testi lezyonlu sol...

Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Merdiven ve Silindir Testi: Yeni Bir Yaklaşım Hemiparkinsonian Rat Derin beyin stimülasyonu Etkileri Motor Sonuçlarını Değerlendirmek için

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

a-novel-approach-to-assess-motor-outcome-deep-brain-stimulation

Research

JoVE Journal

Behavior

14.6K Görüntüleme.  University Hospital Wuerzburg. Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

Video: A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

Parkinson Hastalığı Fare Modeller Duyusal Motor Fonksiyon Değerlendirilmesi

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

Davranış

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

Derin beyin stimülasyonu Cerrahi Uygulanan Uyanık İnsanlar İntraoperatif Davranış Görevler

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

Tıp

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Three new behavioral tests (forelimb step-alternation, postural instability test, pasta handling test) for evaluating forelimb function after cervical spinal cord injury in rodents are described.

Roman Görevleri kullanılarak tek taraflı Servikal SKY sonra ön ayakları Fonksiyon değerlendirilmesi: Ekstremite Adım münavebe, postural İstikrarsızlık ve Pasta Taşıma

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

Bir fare MPTP kaynaklı Parkinson hastalığı modelinde kendiliğinden hareket davranış değerlendirme

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

Adaptif Derin Beyin Stimülasyonu İle Parkinson Hastalığı kontrol

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

Unilateral Pyramidotomy of the Corticospinal Tract in Rats for Assessment of Neuroplasticity-inducing Therapies

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has great importance for distal muscle control in humans and, to a lesser extent, in rodents. A unilateral cut of one pyramid results in loss of CST innervation of the spinal cord mainly on the contralateral side of the spinal cord leading to transient motor disability in the forelimbs and sustained loss of dexterity. Ipsilateral projections of the corticospinal tract are minor. We have refined our surgical method to increase the chances of lesion completeness. We describe postsurgical care. Deficits on the Montoya staircase pellet reaching test and the horizontal ladder test shown here are detected up to 8 weeks postinjury. Deficits on the cylinder rearing test are only detected transiently. Therefore, the cylinder test may only be suitable for detection of short term recovery. We show how, electrophysiologically and anatomically, one may assess lesions and plastic changes. We also describe how to analyse fibers from the uninjured CST sprouting across the midline into the deprived areas. It is challenging to obtain &#62;90% complete lesions consistently due to the proximity to the basilar artery in the medulla oblongata and survival rates can be low. Alternative surgical approaches and behavioural testing are described in this protocol. The pyramidotomy model is a good tool for assessing neuroplasticity-inducing treatments, which increase sprouting of intact fibers after injury.

The corticospinal tract, one of the major sensorimotor tracts, can be lesioned unilaterally in the rodent brainstem in order to test neuroplasticity-inducing therapies for the central nervous system. This surgical procedure (&#8220;pyramidotomy&#8221;) and postoperative assessments are described in this protocol.

Nöroplastisite uyaran Tedaviler Değerlendirme Sıçanlarda Kortikospinal Yolu Tek Taraflı Pyramidotomy

The corticospinal tract (CST) can be completely severed unilaterally in the medullary pyramids of the rodent brainstem. The CST is a motor tract that has ...

Nörobilim

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS.

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

Ön Talamusun Çekirdek Derin Beyin Stimülasyon sonra Sıçan Hippocampus Gen İfade Değişim Analizi

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective ...

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

İnme ile Alzheimer Hastalığının bir Transgenik Fare Modelinde Motor ve Hipokampal Bağımlı Mekansal Öğrenme ve Referans Hafıza Değerlendirme

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

Rodent Behavioral Testing to Assess Functional Deficits Caused by Microelectrode Implantation in the Rat Motor Cortex

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes demonstrate the ability to record action potentials from individual or small groups of neurons. Such recorded signals have successfully been used to allow patients to interface with or control&#160;computers, robotic limbs, and their own limbs. However, previous animal studies have shown that a microelectrode implantation in the brain not only damages the surrounding tissue but can also result in functional deficits. Here, we discuss a series of behavioral tests to quantify potential motor impairments following the implantation of intracortical microelectrodes into the motor cortex of a rat. The methods for open field grid, ladder crossing, and grip strength testing provide valuable information regarding the potential complications resulting from a microelectrode implantation. The results of the behavioral testing are correlated with endpoint histology, providing additional information on the pathological outcomes and impacts of this procedure on the adjacent tissue.

We have shown that a microelectrode implantation in the motor cortex of rats causes immediate and lasting motor deficits. The methods proposed herein outline a microelectrode implantation surgery and three rodent behavioral tasks to elucidate potential changes in the fine or gross motor function due to implantation-caused damage to the motor cortex.

Kemirgen fonksiyonel açıkları sıçan Motor korteks elektrot implantasyon nedeniyle değerlendirmek için sınama davranış

Medical devices implanted in the brain hold tremendous potential. As part of a Brain Machine Interface (BMI) system, intracortical microelectrodes ...

Biyomühendislik

The 6-hydroxydopamine Rat Model of Parkinson's Disease

Motor symptoms of Parkinson's disease (PD)-bradykinesia, akinesia, and tremor at rest-are consequences of the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and dopaminergic striatal deficit. Animal models have been widely used to simulate human pathology in the laboratory. Rodents are the most used animal models for PD due to their ease of handling and maintenance. Moreover, the anatomy and molecular, cellular, and pharmacological mechanisms of PD are similar in rodents and humans. The infusion of the neurotoxin, 6-hydroxydopamine (6-OHDA), into a medial forebrain bundle (MFB) of rats reproduces the severe destruction of dopaminergic neurons and simulates PD symptoms. This protocol demonstrates how to perform the unilateral microinjection of 6-OHDA in the MFB in a rat model of PD and shows the motor deficits induced by 6-OHDA and predicted dopaminergic lesions through the stepping test. The 6-OHDA causes significant impairment in the number of steps performed with the contralateral forelimb.

The 6-hydroxydopamine (6-OHDA) model has been used for decades to advance the understanding of Parkinson's Disease. In this protocol, we demonstrate how to perform unilateral nigrostriatal lesions in the rat by injecting 6-OHDA in the medial forebrain bundle, assess motor deficits, and predict lesions using the stepping test.

Parkinson Hastalığının 6-hidroksidopamin Sıçan Modeli

Motor symptoms of Parkinson's disease (PD)-bradykinesia, akinesia, and tremor at rest-are consequences of the neurodegeneration of dopaminergic neurons in ...