Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion

Objective Neurotrophin‐3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move toward the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke. Methods Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically feasible time to treatment, 24 hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for 4 weeks using implanted catheters and minipumps. Results Radiolabeled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. Functional magnetic resonance imaging during stimulation of the affected wrist showed spontaneous recovery of peri‐infarct blood oxygenation level–dependent signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways. Interpretation Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke

Вестник Сысертского городского округа. 2018. № 23

Once it is appreciated that it is not possible for an all-powerful, all-knowing, all-loving God to exist, the important question arises: What does exist that is closest to, and captures the best of what is in, the traditional conception of God? In this paper I set out to answer that question. The first step that needs to be taken is to sever the God-of-cosmic-power from the God-of-cosmic-value. The first is Einstein’s God, the underlying dynamic unity in the physical universe which physics seeks to depict by means of a true, unified, physical “theory of everything”. Science has already achieved some theoretical knowledge of this God-of-cosmic-power. The second is what is of most value in our human world, and in the world of sentient life more generally. Having cut God in half in this way, our fundamental problem, intellectual and practical, becomes: How can the God-of-cosmic-value (as it is represented on earth at least) exist and best flourish within the God-of-cosmic-power? Or, in other words: How can what is of value associated with human life – and sentient life more generally – exist and best flourish within the physical universe? Clearly acknowledging that this is our fundamental problem, in academic inquiry, and in all that we do, might help what is of value in life to flourish rather better than it does at present

Israeli and Palestinian stories. Can mediators reconfigure incompatible narratives?

The rise of further tensions and wars in the Middle East interconnects, oversimplifies and radicalizes narratives. The aim of the article is to question the scope and practical limits of the mediators’ power regarding parties’ representations of the past. The study is divided into four parts. The first describes the specific challenge faced by practitioners. The other parts explore the Israeli-Palestinian case, focusing on three distinct approaches to contradictory narratives. The first can be summarized by the formula ‘neither nor’ (neither the Israeli narrative, nor the Palestinian narrative). In concealing interpretations of the past, mediators try to do away with the ‘tyranny of the past’. The second approach takes into consideration ‘both the Israeli and the Palestinian narratives’. It tends to be inclusive and to consider all interpretations of the past. The third and last approach applies a ‘on the one hand, on the other hand’ reasoning in order to forge new interpretations of the past. At each stage of the research, the purpose is to question the actual impact of these approaches. Do they enable the parties to move on, or do they reinforce the deadlock? Do they open the minds of the negotiators or do they rather close them