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

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.

Fluoxetine-induced recovery of serotonin and norepinephrine projections in a mouse model of post-stroke depression

“…However, since both GABAergic interneurons and glutamatergic neurons receive excitatory (PSD95+) and GABA (Gephyrin+) synapses the identity of the neurons innervated by 5-HT projection is not identified using our method. Nevertheless, this specificity mirrors FLX-induced restoration of inhibitory-excitatory balance in the mPFC 35 and argues for a functional role for these contacts in behavioral recovery 22 .…”

Effects of the prophylactic use of escitalopram on the prognosis and the plasma copeptin level in patients with acute cerebral infarction

“…Its rapid onset, efficacy, safety, and tolerance have been widely verified. In recent years, some clinical studies have shown that the early use of SSRI antidepressants not only significantly reduces the incidence of PSD, which is independent of its antidepressant effects, but also promotes neuronal regeneration and plasticity changes, comprehensively improving the post-stroke motor, emotional regulation, cognitive, and social functions, together with the prognosis of stroke (4)(5)(6)(7)(17)(18)(19). In addition, some studies have shown that the earlier antidepressant drugs are used after ischemic stroke, the better the rehabilitation effect will be (17,18), while delayed administration might miss the best rehabilitation opportunity.…”

“…Some clinical evidence has shown that the early prophylactic use of selective serotonin reuptake inhibitors (SSRIs) in patients with cerebral infarction can not only prevent the occurrence of post-stroke depression (PSD), but also promote neurological rehabilitation, especially motor function of patients without depression after cerebral infarction, and thereby improve the prognosis (4)(5)(6)(7). Previous research has suggested that SSRIs might regulate the function of the hypothalamic-pituitary-adrenal (HPA)-axis in the treatment of depression (8).…”

Principles and global experience of applying robotic rehabilitation technologies in patients after stroke

“…Обучение простым и сложным двигательным актам пациентов после ОНМК с использованием современных роботизированных комплексов индуцирует пластичность нейронов двигательной коры больших полушарий мозга за счет внешнего стимулирующего воздействия. Именно способность центральной нервной системы к длительной или постоянной модификации функций или структурной реорганизации ее ýлементов является основополагающим механизмом в способности мозга к научению [19][20][21][22].…”