SSRI and Motor Recovery in Stroke: Reestablishment of Inhibitory Neural Network Tonus.

Camila B Pinto,Erica C Camargo,Polyana V De Toledo Piza,Qing M Wang,Faddi G Saleh Velez,Fernanda Lopes,Felipe Fregni,Nicole L Mazwi,Laura Dipietro,Randie Black-Schaffer

doi:10.3389/fnins.2017.00637

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control; these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation.

Highlights

Stroke is the second cause of death worldwide and the leading cause of death in upper-middle income countries; about 6.7 million people died from stroke in 2013 in the US (Mozaffarian et al, 2016)
While the exact mechanisms of action of selective serotonin reuptake inhibitors (SSRIs) on the neural system after stroke are far from being understood, this review aims to discuss the potential role of SSRIs on inhibitory neural circuits as a possible mechanism underlying motor rehabilitation after stroke through cortical reorganization and enhancement of motor learning
Prolonged paroxetine treatment (30 days 20 mg per day) induced hypo activation of S1M1 cells, but still resulted in improvement in finger tapping motor task (Gerdelat-Mas et al, 2005). These results indicate that SSRIs may have an acute effect on excitatory circuits that is led by enhancement of inhibitory activity

Summary

INTRODUCTION

Stroke is the second cause of death worldwide and the leading cause of death in upper-middle income countries; about 6.7 million people died from stroke in 2013 in the US (Mozaffarian et al, 2016). Two main neurophysiological changes have been associated with brain remodeling and recovery after stroke: (i) an initial increase in excitability in cortical regions and perilesional areas not affected by the stroke, and (ii) increased activity/excitability in the contralesional hemisphere In this context, several studies showed that in stroke patients the inhibitory function is globally reduced in both hemispheres suggesting that the modulation of inhibitory circuits might result from a strategy that aims at compensating for motor impairment (Talelli et al, 2006; Di Lazzaro et al, 2012; Takeuchi and Izumi, 2012). That shift may be an index of cortical disorganization

A Network Example of Disrupted Excitation-Inhibition Balance

Findings

SUMMARY