Neurotransmitters and motor activity: Effects on functional recovery after brain injury

Goldstein, Larry B.

doi:10.1016/j.nurx.2006.07.010

Cited by 34 publications

(23 citation statements)

References 73 publications

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“…These body movements are present in the locomotor function of the rat [44] and may be qualitatively measured by the beam-walking test [30,45,46]. It has been documented that focal cortical damage in rats induces a temporary motor deficit [7,22,30,31,47]. The results of the present work revealed that cortical iron injection resulted in a motor deficit for 8 days.…”

Section: Figmentioning

confidence: 48%

“…Our findings show that LP and motor deficit may indicate impaired neuronal connectivity in the corticospinal and CPC tracts resulting from cortical damage from iron in the cortex. Previously, it had been suggested that the noradrenergic system facilitates recovery in injured animals [6,7,22,32,47,48] because noradrenergic drugs facilitate motor recovery in injured rats [6,18,48]. However, evidence linking cerebellar 5-HT dysfunction to behavioral deficits remains scarce.…”

Section: Figmentioning

confidence: 99%

“…The described changes occur under specific conditions of experimental injury. In this framework, it has been proposed that recovery of motor function after focal cortical injury would accompany the functional restoration of neuronal groups located in regions that are remote from, but anatomically related to, the injured site [7,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Recovery of Motor Deficit, Cerebellar Serotonin and Lipid Peroxidation Levels in the Cortex of Injured Rats

Bueno-Nava¹,

González-Piña

Alfaro-Rodríguez³

et al. 2010

Neurochem Res

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The sensorimotor cortex and the cerebellum are interconnected by the corticopontocerebellar (CPC) pathway and by neuronal groups such as the serotonergic system. Our aims were to determine the levels of cerebellar serotonin (5-HT) and lipid peroxidation (LP) after cortical iron injection and to analyze the motor function produced by the injury. Rats were divided into the following three groups: control, injured and recovering. Motor function was evaluated using the beam-walking test as an assessment of overall locomotor function and the footprint test as an assessment of gait. We also determined the levels of 5-HT and LP two and twenty days post-lesion. We found an increase in cerebellar 5-HT and a concomitant increase in LP in the pons and cerebellum of injured rats, which correlated with their motor deficits. Recovering rats showed normal 5-HT and LP levels. The increase of 5-HT in injured rats could be a result of serotonergic axonal injury after cortical iron injection. The LP and motor deficits could be due to impairments in neuronal connectivity affecting the corticospinal and CPC tracts and dysmetric stride could be indicative of an ataxic gait that involves the cerebellum.

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Section: Figmentioning

confidence: 48%

Section: Figmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Recovery of Motor Deficit, Cerebellar Serotonin and Lipid Peroxidation Levels in the Cortex of Injured Rats

Bueno-Nava¹,

González-Piña

Alfaro-Rodríguez³

et al. 2010

Neurochem Res

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“…19 Other drugs affecting central neurotransmitters, when combined with training, may also modulate the recovery process. 20 Most clinical acute stroke trials, including ICTUS, do not control or account for the potential effects of poststroke physiotherapy or the use of other drugs that might affect functional recovery, and ICTUS did not require that a particular physiotherapeutic intervention be tied to drug administration.…”

Section: Strokementioning

confidence: 99%

Poststroke Pharmacotherapy

Goldstein

2012

Stroke

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T he term ictus, used medically to denote a stroke or seizure, is a Latin word meaning "a blow." Unfortunately, this definition is also an appropriate descriptor of the International Citicoline Trial on Acute Stroke (ICTUS) 1 -its results are another blow to the search for a safe and effective pharmacological approach for augmenting the clinical benefit of acute reperfusion therapy in patients with ischemic stroke or improving outcomes for those who cannot be recanalized. This carefully designed and conducted, multicenter, doubleblind, randomized trial found that, "citicoline is not efficacious in the treatment of moderate-to-severe acute ischemic stroke," (primary outcome for intention-to treat with citicoline based on a global outcome statistic including the National Institute of Health Stroke Scale, modified Rankin score, and Barthel index; odds ratio, OR=1.03, 95% CI, 0.86-1.25). 1Although referred to as a new drug in the ICTUS report, experimental and clinical data related to citicoline's putative mechanisms of action and potential therapeutic effects have accrued over the last 4 decades.2,3 Exogenous citicoline (cytidine-5′-diphosphocholine) is hydrolyzed to cytidine and choline, rephosphorylated, and then resynthesized by cytidine triphosphate-phosphocholine cytidylyl transferase. 4 Citicoline is the rate limiting intermediate for the synthesis of phosphatidylcholine, an important membrane phospholipid.4 Although brain levels of citicoline after parenteral or oral administration are unknown, about 0.5% of total radioactivity of orally administered radiolabeled citicoline is incorporated into brain tissue compared with about 2% of an intravenous dose. 5In contrast to acute reperfusion interventions such as pharmacological thrombolysis or mechanical clot retrieval, treatment with citicoline had the potential to improve stroke outcomes through both neuroprotective (aimed at reducing the extent of ischemic injury) and neurorestorative (approaches affecting brain plasticity during the recovery process) effects. Neuroprotective actions of citicoline are hypothesized, at least in part, to be mediated through an attenuation of phospholipase A2 activation, preserving mitochondrial membrane cardiolipin, increasing phosphatidylcholine levels, raising glutathione synthesis and glutathione reductase activity, decreasing lipid peroxidation, and improving Na + /K + -ATPase activity.5 Neurorestorative actions may facilitate neural repair and postinjury neuroplasticity in addition to having effects on neurotransmitters such as acetylcholine and dopamine. 5,6 Even before ICTUS, citicoline had been studied in >11 000 patients and volunteers. 1 The theoretical benefits for patients with ischemic stroke were supported by a patient-level pooledanalysis of data from 4 randomized trials (n=1372) that showed a treatment-associated one-third improvement in 3-month outcomes (OR=1.33; 95% CI, 1.10-1.62; P=0.0034), 7 and a studylevel meta-analysis of 5 trials (n=1921) showing a 29% reduction in long-term death or disability (OR=0.71,...

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“…Issues such as drug dose, timing of the intervention as well as its duration and intensity, patient comorbidity, and the location and extent of brain injury, among other factors, may be significant. 6,19,20 It is therefore not surprising that the results of small clinical trials of the effects of amphetamine on poststroke recovery in humans have been inconsistent, but mostly negative. 6 The Amphetamine Enhanced Stroke Recovery Trial, a National Institutes of Health-supported pilot clinical trial, is attempting to address some of the issues necessary for the design of a large prospective trial.…”

mentioning

confidence: 99%

The 2009 Feinberg Lecture

Goldstein

2009

Stroke

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Background and Purpose-This annual Feinberg Award lecture is intended to present examples of the broad scope of stroke-related research and to show how different investigative approaches can advance the field to improve stroke patient's outcomes. In keeping with one of the objectives of the American Heart/American Stroke Association, this lecture also provides a perspective and highlights opportunities for beginning clinical investigators. Summary of Report-Clinically, the continuum of stroke research and care can be divided into primary prevention, acute interventions, secondary prevention, and poststroke recovery. From a technical/methodological standpoint, fundamental laboratory studies yield insights into basic disease mechanisms and applied laboratory studies further explore the biological basis of disease and evaluate possible therapeutic interventions. The results of these laboratory-based observations can inform clinical study design whereas questions raised by clinical observations can be explored in laboratory experiments (ie, "translational" research). Additional information is gained through observational, interventional, and synthetic (eg, meta-analytic) clinical studies. Outcomes/effectiveness research determines how well interventions perform in different "real-world" settings. The discussion provides examples of how several of these approaches can be used to address various research questions. The importance for stroke investigators to contribute to related public policy issues is also reviewed. Conclusions-This is an exciting era for clinical investigators studying stroke and for those at the beginning stages of their careers. Whether taking a broad-based research approach or working on a specific, focused question, our combined efforts are leading to improved outcomes for patients with stroke, the very goal of Bill Feinberg's career.

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Neurotransmitters and motor activity: Effects on functional recovery after brain injury

Cited by 34 publications

References 73 publications

Recovery of Motor Deficit, Cerebellar Serotonin and Lipid Peroxidation Levels in the Cortex of Injured Rats

Recovery of Motor Deficit, Cerebellar Serotonin and Lipid Peroxidation Levels in the Cortex of Injured Rats

Poststroke Pharmacotherapy

The 2009 Feinberg Lecture

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