Neurothrombectomy in acute ischaemic stroke: a prospective single-centre study and comparison with randomized controlled trials.

BACKGROUND AND PURPOSE: In the last few months five multicentre, randomized controlled trials (RCTs) unequivocally showed the superiority of mechanical thrombectomy in large vessel occlusion acute ischaemic stroke compared to systemic thrombolysis. Despite varying inclusion criteria and time intervals from onset to revascularization overall increases of good functional outcome between 55% and 81% were reported. However, only a minority of screened patients (approximately 1%) were eligible for intra-arterial (IA) therapy. METHODS: An investigator-initiated, single-centre, prospective and blinded end-point analysis was performed of 3123 consecutive patients with acute ischaemic stroke presenting between February 2010 and December 2014. RESULTS: One hundred and fifty-four patients [4.9%, age (years) mean (SD), median (interquartile range) 71.2 (±14), 74.7 (65.9-81.4)] met the inclusion criteria of sparse early ischaemic signs on initial standard cranial computed tomography (CT) (ASPECT score ≥7), large vessel occlusion in the anterior circulation on CT angiography and start of treatment within 6 h of onset of symptoms. After consensual interdisciplinary treatment decisions 130 patients (4.2%) received IA treatment - in the majority stent-assisted thrombectomy in combination with intravenous (IV) recombinant tissue plasminogen activator - and 24 patients (0.7%) standard IV thrombolysis. On 3 months' follow-up an overall significant improvement of disability (P = 0.05) as measured by the modified Rankin Scale was shown in favour of the IA treatment group. Good functional outcome was achieved in about twice as many patients (IA vs. IV, 41.2% vs. 21.2%; P = 0.078). CONCLUSION: By choosing pragmatic inclusion criteria state-of-the-art IA therapy of a specialized tertiary stroke centre can be safely applied under real-world conditions to a higher percentage of patients with similar success to the recently published RCTs.

Dendrodendritic inhibition through reversal of dopamine transport.

Synapses in the central nervous system are usually defined by presynaptic exocytotic release sites and postsynaptic differentiations. We report here a demonstration of dendrodendritic inhibition that does not engage a conventional synapse. Using amperometric and patch-clamp recordings in rat brain slices of the substantia nigra, we found that blockade of the dopamine transporter abolished the dendritic release of dopamine and the resulting self-inhibition. These findings demonstrate that dendrodendritic autoinhibition entails the carrier-mediated release of dopamine rather than conventional exocytosis. This suggests that some widely used antidepressants that inhibit the dopamine transporter may benefit patients in the early stages of Parkinson's disease.

Limitations of cellular models in Parkinson's disease research.

Cell cultures for Parkinson's disease research have the advantage of virtually unlimited access, they allow rapid screening for disease pathogenesis and drug candidates, and they restrict the necessary number of animal experiments. Limitations of cell cultures, include that the survival of neurons is dependent upon the culture conditions; that the cells do not develop their natural neuronal networks. In most cases, neurons are deprived from the physiological afferent and efferent connections. In Parkinson's disease research, mesencephalic slice cultures, primary immature dopaminergic neurons and immortalized cell lines--either in a proliferating state or in a differentiated state--are used. Neuronal cultures may be plated in the presence or absence of glial cells and serum. These different culture conditions as well as the selection of outcome parameters (morphological evaluation, viability assays, biochemical assays, metabolic assays) have a strong influence on the results of the experiments and the conclusions drawn from them. A primary example is the question of whether L-Dopa is toxic to dopaminergic neurons or whether it provides neurotrophic effects: In pure, neuronal-like cultures, L-Dopa provides toxicity, whereas in the presence of glial cells, it provides trophic effects when applied. The multitude of factors that influence the data generated from cell culture experiments indicates that in order to obtain clear-cut and unambiguous results, investigators need to choose their model carefully and are encouraged to verify their main results with different models.