Dopamine agonist and stroke recovery

Stroke is a leading cause of human death and disability, with around 30% of stroke patients develop neuropsychological/neuropsychiatric symptoms, such as post-stroke depression (PSD). Basic and translational research on post-stroke psychological disorders is limited. In a focal ischemic stroke mouse model with selective damage to the sensorimotor cortex, sensorimotor deficits develop soon after stroke and spontaneous recovery is observed in 2-4 weeks. We identified that mice subjected to a focal ischemic insult gradually developed depression/anxiety like behaviors 4 to 8 weeks after stroke...

A dopamine D2 receptor agonist, pramipexole, has been found to elicit neuroprotection in patients with Parkinson's disease and restless leg syndrome. Recent evidence has shown that pramipexole mediates its neuroprotection through mitochondria. Considering this, we examined the possible mitochondrial role of pramipexole in promoting neuroprotection following an ischemic stroke of rat. Male Wistar rats underwent transient middle cerebral artery occlusion (tMCAO) and then received pramipexole (0.25 mg and 1 mg/kg body weight) at 1, 6, 12 and 18 h post-occlusion...

BACKGROUND: Dopamine is a key modulator of striatal function and learning and might improve motor recovery after stroke. Previous small trials of dopamine agonists after stroke provide equivocal evidence of effectiveness on improving motor recovery. We aimed to assess the safety and efficacy of co-careldopa plus routine occupational and physical therapy during early rehabilitation after stroke. METHODS: This double-blind, multicentre, randomised controlled trial of co-careldopa versus placebo in addition to routine NHS occupational and physical therapy was done at 51 UK NHS acute inpatient stroke rehabilitation services...

Upon ischaemic stroke, brain-resident and peripheral immune cells accumulate in the central nervous system (CNS). Interestingly, these cells express pattern specific to neurotransmitter receptors and, therefore, seem to be susceptible to neurotransmitter stimulation, potentially modulating their properties and functions. One of the principal neurotransmitters in the CNS, dopamine, is involved in the regulation of processes of brain development, motor control and higher brain functions. It is constantly released in the brain and there is experimental and clinical evidence that dopaminergic signalling is involved in recovery of lost neurological function after stroke...

RATIONALE: Holmes' tremor is an uncommon neurologic disorder following brain insults, and its pathogenesis is undefined. The interruption of the dento-rubro-thalamic tract and secondary deterioration of the nigrostriatal pathway are both required to initiate Holmes' tremor. We used nuclear medicine imaging tools to analyze a patient with concurrent infarction in different zones of each side of the thalamus. Finding whether the paramedian nuclear groups of the thalamus were injured was a decisive element for developing Holmes' tremor...

Functional recovery after a stroke is important for patients' quality of life. Not only medical care during the acute phase, but also rehabilitation during the chronic phase after a stroke is important. However, the mechanisms underlying functional recovery, particularly the chronic phase after stroke, are still not fully understood. Thus, further basic study on brain after focal stroke is necessary. In this study, we found that the concentration of dopamine (DA) increased during first week after a stroke in the hemisphere contralateral in the site of stroke by in vivo microdialysis...

Among the many pathophysiologic consequences of traumatic brain injury are changes in catecholamines, including dopamine, epinephrine, and norepinephrine. In the context of TBI, dopamine is the one most extensively studied, though some research exploring epinephrine and norepinephrine have also been published. The purpose of this review is to summarize the evidence surrounding use of drugs that target the catecholaminergic system on pathophysiological and functional outcomes of TBI using published evidence from pre-clinical and clinical brain injury studies...

Treatment with levodopa enhances functional recovery after experimental stroke but its mechanisms of action are elusive. Reactive astrocytes in the ischemic hemisphere are involved in mechanisms promoting recovery and also express dopamine 1 (D1) and dopamine 2 (D2) receptors. Here we investigated if the activation of astrocytic dopamine receptors (D1 and D2) regulates the expression of glial cell line-derived neurotrophic factor (GDNF) after combined in vitro hypoxia/aglycemia (H/A) and studied the expression of GDNF in the ischemic brain after treatment with levodopa/benserazide following transient occlusion of the middle cerebral artery (tMCAO) in the rat...

In adult stroke models, 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a sigma receptor agonist, attenuates activity of neuronal nitric oxide synthase (nNOS), blunts ischemia-induced nitric oxide production, and provides neuroprotection. Here, we tested the hypothesis that PPBP attenuates neuronal damage in a model of global hypoxia-ischemia (H-I) in newborn piglets. Piglets subjected to hypoxia followed by asphyxic cardiac arrest were treated with saline or two dosing regimens of PPBP after resuscitation. Sigma-1 receptors were found in striatal neurons...

In this contribution, we first provide an overview of general principles of reorganisation in the human brain, and point out possible biomarkers of recovery. Subsequently, we expand on possibilities of adjuvant therapy in human rehabilitation using cortical stimulation and pharmacological treatments. Finally, we suggest future directions for research in this field.

Pharmacological agents, known to modulate practice-dependent plasticity in animal models of brain damage, have recently received increased interest for treatment of motor recovery after stroke. The present paper gives an overview of agents that are currently available. Amphetamines have been repeatedly shown to promote recovery of function in animals, but clinical data remain inconclusive. Other pharmacological agents evaluated for motor recovery include selective norepinephrine re-uptake inhibitors, dopamine, dopamine agonists, cholinergic substances, serotonin re-uptake inhibitors, and granulocyte-colony stimulating factor...

Impairment of language function (aphasia) is one of the most common neurological symptoms after stroke. Approximately one in every three patients who have an acute stroke will suffer from aphasia. The estimated incidence and prevalence of stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia often results in significant disability and handicap. It is a major obstacle for patients to live independently in the community. When recovery from aphasia occurs, it is usually incomplete and patients are rarely able to return to full employment and other social activities...

This article describes the state of the science in stroke rehabilitation dealing with three main topics: (1) General approach to stroke rehabilitation (stroke services and stroke units), (2) Neurophysiological and pharmacological interventions (facilitation of brain repair mechanisms) and (3) Experimental approaches (neuronal transplantation). Stroke rehabilitation is an active process beginning during acute hospitalisation, progressing to a systematic program of rehabilitation services and continuing after the individual returns to the community...

Since serotonin (5-HT) stimulates motor function, pharmacological potentiation of 5-HT neurotransmission may improve motor function in healthy subjects and, possibly, recovery in post-stroke patients. Indeed, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increased activation in executive motor areas of healthy subjects as fenozolone, a releaser of monoamines (including noradrenaline, dopamine, and serotonin) from intracellular stores. This study is intended to test the hypothesis that paroxetine can likewise modulate brain motor activity in a dose-dependent manner in healthy subjects...

PURPOSE: Visuospatial inattention or sensory neglect is a common impairment following cerebrovascular accident and is thought to negatively impact on functional recovery and long-term outcome. This review examines various rehabilitative interventions available for the management of visuospatial inattention and the literature that supports their efficacy. METHOD: Medical literature review. RESULTS: Therapies geared toward improved visual scanning and 'retraining' of patients to attend to the neglected field are the mainstay of current therapy...

BACKGROUND AND PURPOSE: Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats. METHODS: MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 microL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle...

OBJECTIVE: Because studies have shown some positive effects of the dopaminergic agent bromocriptine for improving verbal production in patients with nonfluent aphasia, we examined its effect in a patient with an atypical form of crossed nonfluent aphasia from a right hemisphere lesion. DESIGN: Open-label single-subject experimental ABAB withdrawal design. PATIENT: A right-handed man who, after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia, and limb apraxia...

The mechanisms that enhance recovery from brain lesion are more and more precise. The role of neurotransmitters and post-synaptic receptors are essential. Different drugs acting at the level of synapses are potentially useful but still few used in neurorehabilitation. The aim of this article is to review the drugs that can be prescribed in selected situation. In spite of encouraging results of numerous studies, a lot of questions remain and prove the need of large randomised studies to determine the real benefit of drugs in rehabilitation...

The objectives of this study were to investigate the efficacy of bromocriptine (BR) combined with speech therapy (ST) to improve a late recovery in non-fluent aphasic stroke patients. We performed a double-blind study with high dosage of BR, prescribed according to a dose-escalating protocol, comprehensive of clinical data, relatives' impression, and language evaluations. The study was divided into the following phases: t-0, inclusion; t-30, language re-test to evaluate the stability of aphasia; t-90, placebo (PL) and ST; t-150, BR and ST; t-210, BR; t-270, wash-out...

In the present studies, the efficacy of dopexamine hydrochloride, a novel DA1-receptor and beta 2-adrenoceptor agonist in preventing deterioration of cardiovascular function in a canine model of hemorrhagic shock was investigated. Pentobarbital-anesthetized dogs were allowed to bleed into a height-regulated reservoir and the hypotensive state (about 40 mmHg) was maintained for a period of 150 min. Subsequently, blood was reinfused and recoveries in various hemodynamic variables were monitored for an additional period of 120 min...