Der Verlauf motorischer Erholung nach Schlaganfall – eine tierexperimentelle Studie am Rattenmodell

Die vorliegende Arbeit beschreibt motorische Rehabilitation nach Schlaganfall in einem Rattenmodell. In dem Verhaltensexperiment werden zwei unterschiedliche Testgruppen untersucht. Die eine Versuchstiergruppe (Training-Schlaganfall-Training, TST) hat einen einhändigen Greifversuch zunächst vor einer ischämischen Läsion des motorischen Kortex lernen müssen, um diesen nach der Läsion mittel Training wieder zu rehabilitieren. Die andere Versuchstiergruppe (Schlaganfall-Training, ST) hat vor dem Schlaganfall kein spezifisches Training erhalten und den Greifversuch erst nach der Läsion komplett neu erlernt. Ziel dieser Arbeit ist es, motorisches Lernen und motorische Rehabilitation in einem Verhaltensexperiment bestmöglich miteinander zu vergleichen. In den Resultaten zeigt sich, dass alle Tiere in der Lage sind, den Greifversuch nach dem Schlaganfall zu rehabilitieren, respektive neu zu lernen. Auffallend ist, dass die Lernkurve der ST-Tiere im Vergleich zu der TST-Gruppe signifikant früher ansteigt. Es bleibt die Frage, warum nach einer Läsion des motorischen Kortex das Wiederlernen einer bereits gelernten Bewegung langsamer ist als das Neulernen der gleichen Bewegung. Möglicherweise interferieren alte Erinnerungen des Greiftests mit der Rehabilitation des gleichen Tests

Dopamine in Motor Cortex Is Necessary for Skill Learning and Synaptic Plasticity

Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill

Can Anything Good Ever Come From Bearing Migraine Attacks? Suggestions for a Comprehensive Concept of Gain in Migraine

PURPOSE OF REVIEW The purpose of this review is to summarise the current state of knowledge concerning known types of gain, the reasons why patients might seek it, as well as implications for headache disorders. RECENT FINDINGS Even though the subject has been studied in the past, it received less attention in recent years. There is no doubt that migraine is a highly disabling disorder. However, attacks sometimes may be beneficial for the migraine brain as a time-out from the daily routine. On the other hand, patients are often stigmatised as trying to satisfy other needs through their disease. These "other needs" may be the exaggerated seeking for attention and affection or an undue official sickness certificate and were named secondary gain. Striving for secondary gain denotes a behaviour that aims at benefiting from a disease in a way that is seen as inappropriate by others. The fact that the term has persisted in doctors' vocabulary for decades probably indicates that it designates a concept considered relevant by many. However, its usage is complicated by its usually imprecise definition. We found in a literature search that the strive for secondary gain is not limited to neurosis, might both occur consciously and unconsciously, sometimes may aim at financial gain and sometimes at social gain, and can either be potentially expected or readily obtained. This behaviour mainly seems to aim at shaping one's interactions with the environment. Its causes have not been elucidated completely, though, but "unrequited demands for love, attention and affection" have been postulated. The desire for social gain can be influenced by approaches based upon behavioural psychology. Broaching the issue of secondary gain may be beneficial in the daily clinical routine

Both groups acquired the skilled reaching task and achieved a comparable level of performance.

<p>After stroke, both groups showed a similar drop in performance of approximately 50%. Injection of ANI (closed circles) into the peri-infarct cortex at day 12 and 13 induced an impairment of recovery when compared to injections of saline (open circles). Values are presented as mean ± SEM.</p

Schubring2016_fin

Source dat

A small-scale robotic manipulandum for motor training in stroke rats

The investigation and characterization of sensori-motor learning and execution represents a key objective for the design of optimal rehabilitation therapies following stroke. By supplying new tools to investigate sensorimotor learning and objectively assess recovery, robot assisted techniques have opened new lines of research in neurorehabilitation aiming to complement current clinical strategies. Human studies, however, are limited by the complex logistics, heterogeneous patient populations and large dropout rates. Rat models may provide a substitute to explore the mechanisms underlying these processes in humans with larger and more homogeneous populations. This paper describes the development and evaluation of a three-degrees-of-freedom robotic manipulandum to train and assess precision forelimb movement in rats before and after stroke. The mechanical design is presented based on the requirements of interaction with rat kinematics and kinetics. The characterization of the robot exhibits a compact, low friction device, with a sufficient bandwidth suitable for motor training studies with rodents. The manipulandum was integrated with an existing training environment for rodent experiments and a first study is currently underway

A robotic platform to assess, guide and perturb rat forelimb movements

Animal models are widely used to explore the mechanisms underlying sensorimotor control and learning. However, current experimental paradigms allow only limited control over task difficulty and cannot provide detailed information on forelimb kinematics and dynamics. Here we propose a novel robotic device for use in motor learning investigations with rats. The compact, highly transparent, three degree-of-freedom manipulandum is capable of rendering nominal forces of 2 N to guide or perturb rat forelimb movements, while providing objective and quantitative assessments of endpoint motor performance in a 50×30 mm(2) planar workspace. Preliminary experiments with six healthy rats show that the animals can be familiarized with the experimental setup and are able to grasp and manipulate the end-effector of the robot. Further, dynamic perturbations and guiding force fields (i.e., haptic tunnels) rendered by the device had significant influence on rat motor behavior (ANOVA, ). This approach opens up new research avenues for future characterizations of motor learning stages, both in healthy and in stroke models

Identification of dopaminergic terminals in M1.

<p>(a) Western blot analysis of M1 cortical tissue injected with vehicle (sham-lesioned) and 6-OHDA in conjunction with desipramine (i.p.) using tyroxine hydroxylase (TH) reactivity indicated reduced TH expression after elimination of dopaminergic terminals. (b) Quantification of protein expression in DA-lesioned (6-OHDA+D) and sham-lesioned hemispheres reveals reduced protein expression after elimination of dopaminergic terminals. (c) Immunofluorescence staining of cortical dopaminergic terminals (TH immunoreactivity) in an exemplary vehicle and DA-lesioned hemisphere (6-OHDA injections into M1) indicated almost no staining in layer I and II/III and reduced staining in deeper layers in the lesioned M1. Similar findings were obtained in the other two animals treated analogously.</p

Functional D1 and D2 receptors in M1 are necessary for optimal motor skill acquisition but not for movement execution.

<p>(a) Blocking D1 receptors with SCH02339 (green) and D2 receptors with raclopride (blue) or sulpiride (orange) on the second and third day (arrows) of motor skill training significantly impaired reaching success compared to vehicle injected animals (black). When antagonists were discontinued, success rate began to increase normally. No significant differences in success rate existed at day 8 between all 4 groups. Inset: exemplary Nissl stain to verify cannula placement. (b) Raclopride injected into M1 (arrows) after the task had been acquired did not affect the performance. Inset: exemplary Nissl stain to verify injection cannula placement. (c,d) To exclude the possibility that the antagonists spread to other brain regions receiving important DA projections thereby causing the observed learning impairment, raclopride was injected into the dorsal striatum (c, blue) and the prefrontal cortex (d, blue) and compared to vehicle injected controls (black). Skill acquisition was not impaired in these animals. Insets: exemplary Nissl stain to verify cannula placement.</p