Stroke is one of the leading causes of death and adult disability globally, representing one of the highest burdens of disease worldwide. Recent advancements of neuromodulation techniques emerge as promising tools for enhancing stroke recovery, such as transcranial electric stimulation and transcranial magnetic stimulation, which can induce short- and long-term changes of synaptic excitability to restore the impaired functions in stroke patients. The review focuses on discussing the neuroplastic mechanisms of those brain stimulation techniques in stroke rehabilitation, also including some new options for neuromodulation which have great potential in stroke rehabilitation, such as optogenetic stimulation and environmental stimulation. In general, these techniques allow the excitation and synchronization of the neural activity after stroke, which could potentially induce long-term potentiation. As a result, the neuroplastic effect can lead to better functional connection in the brain network in assisting stroke recovery. Future directions include the clarification of the pathways of synaptic plasticity in the whole brain network following neuromodulation after stroke, and investigation of the different roles of distinctive cell populations in neural plasticity enhancement. Additional studies are essential for developing standard protocols in neuromodulation based on a better understanding of the molecular and cellular processes for the ultimate optimization of clinical efficacy.

Stroke patients require rehabilitation programs to improve their functioning and quality of life. Proprioceptive neuromuscular facilitation is a widely used rehabilitation technique in clinical facilities. However, previous studies have not completely clarified its effectiveness. This study aimed to evaluate the effectiveness of proprioceptive neuromuscular facilitation in improving balance and mobility in stroke patients through clinical research and literature review. Our findings show that proprioceptive neuromuscular facilitation techniques effectively improve balance and mobility in stroke patients. However, there is little evidence supporting its superiority over the other rehabilitation methods.

Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive and painless approach that can penetrate deeper structures to improve motor function in people with physical impairment due to stroke. A review of available literature was undertaken to discuss the potential mechanisms of rPMS-based neuromodulation and the application of rPMS in the recovery of motor function (e.g., muscle strength, spasticity, motor control and joint mobility, glenohumeral subluxation) after stroke. Issues of concern about parameters and safety of rPMS were also overviewed. Existing evidence has shown that suprathreshold rPMS can be a potential intervention for motor recovery in patients with stroke because of its neuromodulatory effects. However, the rPMS parameters employed by each research team are highly variable for specific lesions. Thus, more high-quality studies on the optimal rPMS protocols for different impairments are warranted in the future.

Increasing attention has recently been focused on reducing abnormal neuroexcitability in patients with Meige’s syndrome using nerve combing surgery. However, nerve injury caused by nerve combing is of critical concern. Animal studies have shown that stem cells can repair cranial nerves; autologous adipose-derived mesenchymal stem cells have been proved to be safe and effective in clinical trials. A total of 38 patients with Meige’s syndrome were enrolled in this prospective nonrandomized controlled study and divided into a non–stem cell group (n = 30) and a stem cell group (n = 8). Patients in the non-stem cell group underwent facial and trigeminal nerve combing only; patients in the stem cell group underwent adipose-derived mesenchymal stem cell implantation after facial and trigeminal nerve combing. A blepharospasm disability index score was used to evaluate effectiveness of the surgery, and a House–Brackmann grade was used to evaluate facial nerve injury. These data were recorded before the operation and at 7 days, 3 months, and 6 months after the operation. The overall improvement percentage of blepharospasm was 93% at 6-month follow-up in the non-stem cell group. A greater number of nerve combing events during the operation led to better outcomes but increased risk of facial paralysis. Patients in the stem cell group had better facial nerve function at the 6-month follow-up (House–Brackmann grade, P = 0.003) and better blepharospasm improvement at 3 and 6 months than those in the non–stem cell group (blepharospasm disability index score, P = 0.003 and P < 0.001, respectively). Cerebrospinal fluid protein analysis showed that levels of several cytokines were significantly increased after adipose-derived mesenchymal stem cell transplantation, including interleukin-6 (P < 0.01) and interferon gamma-induced protein 10 (P < 0.0001) and the growth factors insulin-like growth factor-1 (P < 0.0001), insulin-like growth factor-binding protein-1 (P < 0.0001), growth/differentiation factor-15 (P < 0.001), and angiopoietin-like 4 (P < 0.001). Facial and trigeminal nerve combing combined with adipose-derived mesenchymal stem cell transplantation is a safe and effective remedy to improve recovery from Meige’s syndrome.

Urinary retention is a serious complication of spinal cord injury. This study examined whether repetitive functional magnetic stimulation (rFMS) applied over the sacral nerve root affected bladder function or mood in patients with urinary retention after spinal cord injury. This single-center, case-control study included 32 patients with detrusor flaccid neurogenic bladder after spinal cord injury, who were randomly assigned to rFMS (n = 11), electroacupuncture pudinal nerve stimulation (EAPNS; n = 11), and control groups (n = 10). All groups received routine bladder function training. The S3 sacral nerve was stimulated at a frequency of 5 Hz, once per day for 4 consecutive weeks in the rFMS group. Electroacupuncture stimulation of the pudendal nerve was performed once daily for 4 weeks in the EAPNS group. The control group received bladder function retraining alone. After the 4-week treatment, there were significant improvements in all three groups (P < 0.05). Primary bladder sensation, maximum bladder volume, maximum bladder pressure, and residual urine were significantly higher in the rFMS group than in the other two groups (P < 0.05). Primary bladder sensation, maximum bladder volume, residual urine, and urinary leukocyte count were significantly different between the EAPNS and control groups (P < 0.05). The rFMS group had significantly lower scores in the self-rated anxiety scale and self-rated depression scale compared with those of the other two groups. The quality of life score significantly increased in all three groups. rFMS is conducive to the recovery of neurogenic function in patients with urinary retention. This study provides a scientific basis for the clinical application and promotion of rFMS.

The traditional Chinese herb, Moschus (also called She Xiang in Chinese), is used to accelerate the rehabilitation of Bell’s palsy (BP) through acupoint sticking therapy in China. However, the mechanism of its effect is not clear. In this study, we explored the pharmacological mechanism using bioinformatics analysis. We identified 59 active ingredients in Moschus using the Traditional Chinese Medicine Integrated Database, including 17-beta-estradiol, testosterone, and 2,6-decamethylene pyridine. In total, 837 differently expressed genes were identified in blood of BP patients by RNA sequencing. Finally, 33 proteins were identified with overlapping predictions by the Comparative Toxicogenomics Database and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine. Proteins of interest were closely associated with 406 Gene Ontology biological processes and 4 pathways. The hub proteins in the protein–protein interaction network were FOS, JUN, proopiomelanocortin, and G protein-coupled estrogen receptor 1. A pharmacology network was constructed with 15 active components of Moschus, 33 protein targets and four pathways. The docking model of androst-4-ene-3,17-dione and FOS-JUN complexes was predicted and constructed. The results indicated testosterone as an effective component of Moschus that may enhance BP rehabilitation by targeting FUN and the mitogen-activated protein kinase and cyclic adenosine monophosphate signaling pathways, and that docking of androst-4-ene-3,17-dione and FOS-JUN complexes might play a critical role. The findings provide a direction for future research to verify the key targets of Moschus in the treatment of BP and an application prospect in the field of facial nerve rehabilitation.

Improved knowledge of the neuroplastic potential of the brain connectome has facilitated the advancement of neuromodulatory treatments for brain tumor patients especially in the perioperative period. More recently, the idea of inducing neuroplastic changes before surgery as “prehabilitation” has been suggested in low-grade gliomas with favorable data. However, it is uncertain the degree to which this treatment with transcranial magnetic stimulation (TMS) would benefit patients with high-grade gliomas, especially with additional rehabilitation after surgery and targets defined by personalized connectomic data. The current report details a case of a patient with recurrent glioblastoma in the right motor area 2 years after previous total resection. Given the desire for a more aggressive recurrent surgery in a highly functional area, the authors decided to proceed with “prehabilitation” by stimulating the surrounding motor cortices around the lesion to turn down the motor cortex connectivity before the recurrent surgery and then completing “rehabilitation” after the surgery. Structural-functional connectomic analyses were completed using Infinitome software based on an individualized patient brain atlas using machine-learning based parcellations. Repetitive TMS was employed, specifically using continuous and intermittent theta burst stimulation protocols. Prehabilitation consisted of using continuous theta burst stimulation at the estimated surgical entry point parcel and intermittent theta burst stimulation at adjacent parcellations for a total of 10 days with 5 sessions per day per target leading up until the surgery. A gross-total resection was obtained, but the patient woke up with left-sided hemiparesis. Resting-state functional magnetic resonance imaging derived connectivity demonstrated a case of a primarily pure cingulate-motor resection causing hemiplegia with an intact corticospinal tract and supplementary motor area. Functional connectivity outliers in cingulate-motor parcels were identified and compared with connectivity matrices from a healthy control atlas. Anomalies, parcels defined as functioning significantly outside a normal range, were chosen as rehabilitation TMS targets to be similarly treated for a total of 10 days with 5 sessions per day per target approximately two weeks after surgery. By using continuous theta burst stimulation on hyperconnected parcels and intermittent theta burst stimulation on hypoconnected parcels, the patient demonstrated significant motor improvement with only 4+/5 strength in the left arm 1 month after surgery. This report demonstrates for the first time the feasibility of using TMS treatment for glioblastoma surgery near “eloquent” cortices as a means of prehabilitation before surgery and rehabilitation after surgery. This parcel-guided approach for TMS treatment based on the cortical site of entry and individualized connectivity analyses allowed for maximal tumor resection and minimal long-term neurologic deficits.