Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study

Scheidtmann, Karl Heinz; Fries, W.; Müller, Friedemann; Koenig, E.

doi:10.1016/s0140-6736(01)05966-9

Cited by 385 publications

(265 citation statements)

References 22 publications

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“…DA, NE, and ACh antagonists degrade practice-dependent plasticity in healthy subjects (Sawaki et al, , 2003Meintzschel and Ziemann, 2006), and retrospective studies strongly suggest that these NMDs are also detrimental in sensorimotor recovery after cerebral stroke (Goldstein et al, 1990;Goldstein, 1995). Conversely, DA, NE, and ACh agonists facilitate practice-dependent plasticity in healthy subjects Flöel et al, 2005a;Meintzschel and Ziemann, 2006) and may be beneficial in stroke rehabilitation (Crisostomo et al, 1988;Walker-Batson et al, 1995;Grade et al, 1998;Scheidtmann et al, 2001;Berthier et al, 2003;Flöel et al, 2005b;Zittel et al, 2007) although this evidence is not undisputed (for review, see Rösser and Flöel, 2008;Berends et al, 2009). The congruence of suppressive effects of NMDs on PASinduced LTP-like plasticity and practice-dependent plasticity suggests that PAS-induced LTP-like plasticity may serve as a biological marker for unfavorable drug effects on motor learning and recovery.…”

Section: Clinical Perspectivementioning

confidence: 99%

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

Korchounov

Ziemann

2011

Neuropsychopharmacol

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Long-term potentiation (LTP) of synaptic efficacy is considered a fundamental mechanism of learning and memory. At the cellular level a large body of evidence demonstrated that the major neuromodulatory neurotransmitters dopamine (DA), norepinephrine (NE), and acetylcholine (ACh) influence LTP magnitude. Noninvasive brain stimulation protocols provide the opportunity to study LTP-like plasticity at the systems level of human cortex. Here we applied paired associative stimulation (PAS) to induce LTP-like plasticity in the primary motor cortex of eight healthy subjects. In a double-blind, randomized, placebo-controlled, crossover design, the acute effects of a single oral dose of the neuromodulatory drugs cabergoline (DA agonist), haloperidol (DA antagonist), methylphenidate (indirect NE agonist), prazosine (NE antagonist), tacrine (ACh agonist), and biperiden (ACh antagonist) on PAS-induced LTP-like plasticity were examined. The antagonists haloperidol, prazosine, and biperiden depressed significantly the PAS-induced LTP-like plasticity observed under placebo, whereas the agonists cabergoline, methylphenidate, and tacrine had no effect. Findings demonstrate that antagonists in major neuromodulatory neurotransmitter systems suppress LTP-like plasticity at the systems level of human cortex, in accord with evidence of their modulating action of LTP at the cellular level. This provides further supportive evidence for the known detrimental effects of these drugs on LTP-dependent mechanisms such as learning and memory.

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Section: Clinical Perspectivementioning

confidence: 99%

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

Korchounov

Ziemann

2011

Neuropsychopharmacol

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“…2 Importantly, and in contrast to the many failed clinical trails using neuroprotective strategies, pharmacological enhancement of brain plasticity has shown efficacy in small clinical trials. 3 Hence, elucidating the fundamental processes regulating or affecting brain plasticity after stroke could provide new therapies that would enhance recovery after stroke for the benefit of a majority of stroke patients.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Ruscher

Kuric

Liu

et al. 2013

J Cereb Blood Flow Metab

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After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3 þ ) and CD3 þ /CD4 þ T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.

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“…Dopamine seems to be effective not only in enhancing working memory in healthy subjects (Barch, 2004) and ameliorating cognitive deficits in the early stages of Parkinson's disease (eg Kulisevsky, 2000) but also in motor recovery after stroke in humans (Scheidtmann et al, 2001) and in boosting of language learning in healthy subjects (Knecht et al, 2004). Even though a small fraction (o5%) of levodopa is hydroxylated to norepinephrine (Nutt and Fellman, 1984), the cardiovascular and plasticity effects of AMPH could thus be dissociated on a molecular level, with the dopamine effects being relevant for brain plasticity.…”

Section: Introductionmentioning

confidence: 99%

D-Amphetamine Boosts Language Learning Independent of its Cardiovascular and Motor Arousing Effects

Breitenstein

Wailke

Bushuven

et al. 2004

Neuropsychopharmacol

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D-Amphetamine (AMPH) was effective in a number of studies on motor and language recovery after stroke, but given safety concerns, its general use after stroke is still debated. Most stroke patients are excluded from treatment because of a significant risk of cardiovascular dysregulation. AMPH acts on multiple transmitter systems, and mainly the noradrenergic actions are related to the cardiovascular effects. If AMPH's cardiovascular and arousal effects were correlated with its plasticity-enhancing effects in humans, this would imply that desired and undesired effects are inevitably tied. If not, improved cerebral reorganization may not be mediated by AMPH's arousing effects and could be achieved with substances lacking the undesired cardiovascular effects. As a model for language recovery after stroke, we used a prospective, randomized, double-blind, placebo-controlled design and taught 40 healthy male subjects an artificial vocabulary of 50 concrete nouns over the course of five consecutive training days (high-frequency training). The associative learning principle involved higher co-occurrences of 'correct' picturepseudoword pairings as compared to 'incorrect' pairings. Subjects received either AMPH (0.25 mg/kg) or placebo 90 min prior to training on each day. Novel word learning was significantly faster and better in the AMPH as compared to the placebo group. Increased learning success was maintained 1 month post-training. No correlation was found between training success and drug-induced increases in blood pressure, heart rate, or a facilitation of simple motor reaction time. Our data show that AMPH's plasticity-enhancing effect in humans is not related to its cardiovascular arousal. This suggests that the beneficial effects in stroke patients could also be obtained by less cardiovascular active drugs.

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Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study

Cited by 385 publications

References 22 publications

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

D-Amphetamine Boosts Language Learning Independent of its Cardiovascular and Motor Arousing Effects

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