The Intersection of Central Dopamine System and Stroke: Potential Avenues Aiming at Enhancement of Motor Recovery

Ok, you've come up with an idea. Whom are you going to go to to get it researched and followed thru to an intervention? I want to know specifically who is the stroke leader in the world.  That person has a hell of a lot of work to do.
https://www.frontiersin.org/articles/10.3389/fnsyn.2018.00018/full?

Annette Gower^1,2,3 and Mario Tiberi^1,2,3*

• ¹Ottawa Hospital Research Institute (Neuroscience Program), Ottawa, ON, Canada
• ²University of Ottawa Brain and Mind Institute, Ottawa, ON, Canada
• ³Departments of Medicine, Cellular and Molecular Medicine, and Psychiatry, University of Ottawa, Ottawa, ON, Canada

Dopamine, a major neurotransmitter, plays a role in a wide range of brain sensorimotor functions. Parkinson's disease and schizophrenia are two major human neuropsychiatric disorders typically associated with dysfunctional dopamine activity levels, which can be alleviated through the druggability of the dopaminergic systems. Meanwhile, several studies suggest that optimal brain dopamine activity levels are also significantly impacted in other serious neurological conditions, notably stroke, but this has yet to be fully appreciated at both basic and clinical research levels. This is of utmost importance as there is a need for better treatments to improve recovery from stroke. Here, we discuss the state of knowledge regarding the modulation of dopaminergic systems following stroke, and the use of dopamine boosting therapies in animal stroke models to improve stroke recovery. Indeed, studies in animals and humans show stroke leads to changes in dopamine functioning. Moreover, evidence from animal stroke models suggests stimulation of dopamine receptors may be a promising therapeutic approach for enhancing motor recovery from stroke. With respect to the latter, we discuss the evidence for several possible receptor-linked mechanisms by which improved motor recovery may be mediated. One avenue of particular promise is the subtype-selective stimulation of dopamine receptors in conjunction with physical therapy. However, results from clinical trials so far have been more mixed due to a number of potential reasons including, targeting of the wrong patient populations(There are never wrong patient populations, your goal is 100% recovery for all. NO survivor left behind.) and use of drugs which modulate a wide array of receptors. Notwithstanding these issues, it is hoped that future research endeavors will assist in the development of more refined dopaminergic therapeutic approaches to enhance stroke recovery.

Introduction

Stroke refers to an interruption of blood supply to some regions of the brain. This can be either ischemic (about 85% of strokes) or hemorrhagic (about 15% of strokes) (Auriat and Colbourne, 2008). Stroke is a major cause of disability in adults. In 2008 stroke was the cause of 5.7 million deaths and 46.6 disability-adjusted life years worldwide (Oczkowski, 2013). Stroke survivors are left with damage to their brain resulting in various impaired domains of function. Among the most common of these is motor deficits, affecting up to 80% of patients (Langhorne et al., 2009). Currently available interventions for stroke include clot-busting approaches such as thrombolytic drugs or angioplasty. These interventions are only available in select cases and only in the hyperacute stage of stroke. Once the patient has stabilized, a combination of spontaneous recovery and rehabilitation allow them to regain some function. While rehabilitation methods such as physical therapy have been shown to be more useful than no rehabilitation at all, no one physiotherapy treatment has been shown to be more efficacious than the others (Oczkowski, 2013). Additionally, physical rehabilitation is only available to individuals who are well enough to complete it. Unfortunately, with currently available treatments, 40–60% of stroke patients still present with motor deficits in the chronic stage, after recovery has plateaued (Acler and Manganotti, 2013). There is a need for more strategies to enhance stroke recovery. One approach, pharmacotherapy, uses drugs and physical rehabilitation to boost recovery. Several classes of drugs have been investigated for this purpose, including selective serotonin reuptake inhibitors (SSRIs), cholinergic agents and dopamine (DA)-enhancing drugs (Rösser and Flöel, 2008; Viale et al., 2018). However, none of these therapies have been approved for routine clinical use in stroke recovery. Herein, we argue that interventions targeting the dopaminergic system hold particular promise. Indeed, stroke impacts the dopaminergic system, and this combined with the normal decline in DA function and motor learning abilities with age, makes it a relevant target. There is robust evidence in animal stroke models showing that DA-enhancing drugs can improve motor recovery, through a myriad of potential mechanisms that remain to be fully understood. Lastly, clinical investigations suggest that this may be a valid therapeutic tool for stroke survivors, although better selection of patient groups may be required. This review will focus on interactions between the dopaminergic system and the poststroke brain, specifically as it pertains to motor recovery. To this end, we have excluded evidence relating to therapeutic targeting of dopaminergic system in the facilitation of recovery from traumatic brain injury.

More at link.