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

Abstract

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 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.

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System

“…In recent years, a growing number of studies have indicated the involvement of dopaminergic systems in stroke modulation (Gower and Tiberi, 2018). The results of microdialysis of the present study demonstrated that cerebral ischemia induced a robust and transient release of DA extracellularly in the striatum, which is consistent with previous studies (Globus et al, 1988;Tsukada et al, 2004;Li et al, 2010;Yoshimoto et al, 2014).…”

“…The CPu is the structure responsible for a wide variety of behavioral functions and is highly vulnerable to ischemia (Globus et al, 1988;Alexander et al, 1990;Sabogal et al, 2014). Lesions in the striatum and transient global ischemia cause significant loss of dopaminergic substantia nigra neurons (Ichitani et al, 1991;Burke et al, 1992;Gower and Tiberi, 2018). In addition, striatal infarction downregulates TH immunoreactivity following ischemia (Yamada et al, 1996;Li et al, 2016;Mao et al, 2017).…”

Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients

“…Lack of response to modafinil in our study may have been the result of a mechanism of action separate from dopamine neurotransmission. Pre-clinical and clinical data suggest dopamine activity is disturbed following acute stroke, and dopamine supplementation or augmentation may be of benefit, but this requires confirmation [13,35].…”

“…Modafinil's effects appear independent of serotonin, dopamine, GABA, adenosine, histamine-3, melatonin, and benzodiazepine receptors. Compared to conventional neurostimulants, modafinil appears to be devoid of dopaminergic effects, which may be of significance as post-stroke dopaminergic system dysfunction has been recently described [12,13].…”

How effective is current pharmacotherapy for motor recovery after stroke?

“…Strategies aimed at inducing brain plasticity and modulating brain activity in order to achieve functional goals are essential as well. Despite post-stroke cures and cares made great strides, there is no clear evidence on the role of pharmacological treatment in post-stroke recovery [6][7][8][9][10][11][12]. Drugs specifically aimed at acting onto neuroplasticity-based recovery mechanisms may indeed have a significant role in this field.…”