Brain–computer interface (BCI) is a novel communication method between brain and machine. It enables signals from the human brain to influence or control external devices. Currently, much research interest is focused on the BCI-based neural rehabilitation of patients with motor and cognitive diseases. Over the decades, BCI has become an alternative treatment for motor and cognitive rehabilitation. Previous studies demonstrated the usefulness of BCI intervention in restoring motor function and recovery of the damaged brain. Electroencephalogram (EEG)-based BCI intervention could cast light on the mechanisms underlying neuroplasticity during upper limb recovery by providing feedback to the damaged brain. BCI could act as a useful tool to aid patients with daily communication and basic movement in severe motor loss cases like amyotrophic lateral sclerosis (ALS). Furthermore, recent findings have reported the therapeutic efficacy of BCI in people suffering from other diseases with different levels of motor impairment such as spastic cerebral palsy, neuropathic pain, etc. Besides motor functional recovery, BCI also plays its role in improving the behavior of patients with cognitive diseases like attention-deficit/hyperactivity disorder (ADHD). The BCI-based neurofeedback training is focused on either reducing the ratio of theta and beta rhythm, or enabling the patients to regulate their own slow cortical potentials, and both have made progress in increasing attention and alertness. With summary of several clinical studies with strong evidence, we present cutting edge results from the clinical application of BCI in motor and cognitive diseases, including stroke, spinal cord injury, ALS, and ADHD.
The prevalence of multiple neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), has been dramatically increasing, particularly in the aging population. However, the currently available therapies merely alleviate the symptoms of these diseases and are unable to retard disease progression significantly. Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years for ameliorating symptoms or interfering with the pathogenesis of aging- associated diseases. Modern pharmacological studies have proved that TCM imparts disease-modifying therapeutic effects against these diseases, such as protection of neurons, clearance of protein aggregates, and regulation of neuroinflammation. This review summarizes the evidence from recent studies on AD and PD therapies regarding the neuroprotective activities and molecular mechanisms of a series of TCM formulations comprising herbs and their active ingredients. The findings of this review support the use of TCM as an alternative source of therapy for the treatment of neurodegenerative diseases.
The central role of the Golgi apparatus in critical cellular processes such as the transport, processing, and sorting of proteins and lipids has placed it at the forefront of cell science. Golgi apparatus dysfunction caused by primary defects within the Golgi or pharmacological and oxidative stress has been implicated in a wide range of neurodegenerative diseases. In addition to participating in disease progression, the Golgi apparatus plays pivotal roles in angiogenesis, neurogenesis, and synaptogenesis, thereby promoting neurological recovery. In this review, we focus on the functions of the Golgi apparatus and its mediated events during neurorestoration.
A literature review of worldwide epidemiology of spinal cord injury (SCI).
To review the epidemiological indicators of SCI, such as incidence, prevalence, demographic characteristics, etiology, level and severity of injury, complications and mortality.
The Department of Orthopaedics, Tianjin Medical University General Hospital, Heping District, Tianjin, People’s Republic of China.
We searched articles published in PubMed, Medline, EMBASE and the Web of Science between January 1993 and June 2017 using the key words “spinal cord injury”, “traumatic spinal cord injury”, “non-traumatic spinal cord injury” and “epidemiology”. The incidence, etiology, prevalence, patient demographics, level and severity of injury, complications and mortality were reviewed from the articles.
The epidemiology of SCI has changed. Motor vehicle accidents and falls have become the most common reasons of injury gradually. Incidence of SCI varies by regions or countries, and it has gradually increased with the expansion of human activities. The number of male patients were significantly more than female, the average age of patients with SCI had a tendency to increase gradually. The cervical level of spine was the most common part of injury; there were more number of patients with tetraplegia than patients with paraplegia. Electrolyte disturbances, pulmonary infections, urinary tract infections and bedsores were the four most common complications.
We must have a greater understanding of epidemiology to implement more preventative measures. The epidemiology in different regions is of significant difference, which may be resulted from economic, science and technology, medical, geographical and even social conditions. Therefore, we must establish appropriate intervention measures according to the particularity of population.
We developed the method of cervical spinal cord decompression through durotomy followed by duroplasty and analyzed its efficacy.
To develop a tactic of decompression durotomy and duroplasty for the treatment of severe spinal cord injury(SCI) with extensive edema of the spinal cord and without intramedullary hematoma, and to demonstrate the effectiveness of this method.
From October 2016 to January 2018, 17 decompression operations were performed in the cervical spine in patients with SCI. Decompression laminectomy was done without durotomy in the first group of patients. In the second group, duroplasty of the spinal cord was performed after decompression durotomy. A total of 17 patients, 16 males (94%) and 1 female (6%), were operated on (ages from 32 to 66 years). The patients were divided into two groups: a control group and an experimental group. We used the ASIA scale for assessing the patients. The mean follow up time is 12 months (8−24 months).
The first group, i.e., the control group consisted of 10 patients who underwent decompression laminectomy without durotomy. The second group, i.e., the experimental group consisted of 7 patients who underwent durotomy followed by duroplasty. In this group, the positive dynamics were observed in 6 patients. Out of 2 patients with ASIA grade “A”, one showed improvement to ASIA grade “C”, and one improved to ASIA “D”. Two patients with ASIA grade “B” showed recovery to ASIA “D”. Two patients with ASIA grade “C” improved to grade “D” while one patient showed no change from ASIA “C”. Durotomy and duroplasty was effective in the experimental group.
The performance of durotomy and duroplasty is an efficient method for the full-scale decompression of the spinal cord and the prevention of edema. This method aims at decreasing intraspinal pressure, as well as preventing ischemia and apoptosis, which is possible for the prevention and treatment of the spinal cord compartment syndrome or spinal cord intramedullary hypertension.
Clinical neurorestorative therapies recently made great progress for patients with spinal cord injury (SCI). This paper systemically reviews historical perspectives, recent advancements and achievements in SCI through key neurorestorative strategies. In this study, a search was performed in the PubMed, Scopus, and Scholar Google search engines using the keywords “neurorestorative strategies”, “spinal cord injury”, “cell therapy”, “neuromodulation”, and “nerve bridges”. Clinical studies published in the English language were included. It is paramount for academic community involved in this field to take the initiative of a multicenter randomized, double-blind, and placebo-control clinical study with high level of evidence-based treatments for most SCI neurorestorative strategies in patient management. It is of utmost need to establish standard therapeutic methods for patients with SCI as early as possible.
Multilineage-differentiating stress-enduring (Muse) cells were discovered in 2010 as a subpopulation of mesenchymal stroma cells (MSCs). Muse cells can self-renew and tolerate severe culturing conditions. These cells can differentiate into three lineage cells spontaneously or in induced medium but do not form teratoma in vitro or in vivo. Central nervous system (CNS) diseases, such as intracerebral hemorrhage (ICH), cerebral infarction, and spinal cord injury are normally disastrous. Despite numerous therapy strategies, CNS diseases are difficult to recover. As a novel kind of pluripotent stem cells, Muse cells have shown great regeneration capacity in many animal models, including acute myocardial infarction, hepatectomy, and acute cerebral ischemia (ACI). After injection into injury sites, Muse cells survived, migrated, and differentiated into functional neurons with synaptic junctions to local neurons and contributed to recovery of function. Furthermore, Muse cell differentiation did not need to be induced pre-transplantation and no tumors were observed post- transplantation. The Muse cell population is promising and may lead to a revolution in regenerative medicine. This review focuses on recent advances regarding the Muse cells therapies in Neurorestoratology and discusses future perspectives in this field.
Through retrospective analysis of the literature on the cell repair of spinal cord injury worldwide, it is found that the mechanism of cell transplantation repairing spinal cord injury is mainly to replace damaged neurons, protect host neurons, prevent apoptosis, promote axonal regeneration and synapse formation, promote myelination, and secrete trophic factors or growth factors to improve microenvironment. A variety of cells are used to repair spinal cord injury. Stem cells include multipotent stem cells, embryonic stem cells, and induced pluripotent stem cells. The multipotent stem cells are mainly various types of mesenchymal stem cells and neural stem cells. Non-stem cells include olfactory ensheathing cells and Schwann cells. Transplantation of inhibitory interneurons to alleviate neuropathic pain in patients is receiving widespread attention. Different types of cell transplantation have their own advantages and disadvantages, and multiple cell transplantation may be more helpful to the patient’s functional recovery. These cells have certain effects on the recovery of neurological function and the improvement of complications, but further exploration is needed in clinical application. The application of a variety of cell transplantation, gene technology, bioengineering and other technologies has made the prospect of cell transplantation more extensive. There is a need to find a safe and effective comprehensive treatment to maximize and restore the patient’s performance.
Cerebral small vessel disease (CSVD) refers to a type of syndrome caused by lesions in perforating arteries, small veins, small arteries, or capillaries, resulting in clinical, imaging, or pathological alterations. The occurrence and development of CSVD are related to various cerebrovascular risk factors, such as metabolism and genetic factors. CSVD is diagnosed based on brain imaging biomarkers; however, biomarkers capable of predicting and diagnosing CSVD early in its progression have not been found. Exploring biomarkers closely related to disease progression is of great significance for early diagnosis, prognosis, prevention, and treatment of CSVD. This article examines the research progress of CSVD biomarkers, from inflammatory biomarkers, coagulation and fibrinolysis markers, biomarkers of endothelial dysfunction, biomarkers related to cerebrospinal fluid, and gene markers.
Cerebral small vessel disease (CSVD) is a pathophysiological process involving small arteries such as cerebellar arteries, arterioles, capillaries, and veinlets. Imaging features vary; they are mainly composed of recent subcortical infarcts, lacunes of presumed vascular origin, white matter hyperintensities (WMHs) of presumed vascular origin, cerebral microbleeds, enlarged perivascular spaces, and global and regional brain atrophy. CSVD is a common cause of vascular cognitive dysfunction, and in its end stage, dementia often develops. CSVD has been a major research hotspot; however, its causes are poorly understood. Neuroimaging markers of CSVD can be used as the basis for etiological analysis. This review highlights the relevance of neuroimaging markers and cognitive impairment, providing a new direction for the early recognition, treatment, and prevention of cognitive dysfunction in small cerebral angiopathy.
As with all tissues of the central nervous system, the low regeneration ability of spinal cord tissue after injury decreases the potential for repair and recovery. Initially, in spinal cord injuries (SCI), often the surgeon can only limit further damage by early surgical decompression. However, with the development of basic science, especially the development of genetic engineering, molecular biology, tissue engineering, and materials science, some promising progress has been made in promoting the repair of central nervous system injuries. For example, transplantation of neural stem cells (NSCs), olfactory ensheathing cells (OECs), and gene- mediated transdifferentiation to repair central nervous system injury. This paper summarizes the progress and prospects of SCI repair with tissue engineering scaffold and cell transdifferentiation from an extensive literatures.
Dural defects are a common problem in clinical practice, and various types of dural substitutes have been used to deal with dural defects. These play an important role in dural repair. Dural substitutes have gradually reached researchers, neurosurgeons, and patients for approval. This article summarizes the structural characteristics of the dura mater and its regeneration after injury, and reviews the state of progress in research and application. It will provide a reference for the development and application of dural substitutes.
The objective of this study was to document the impact of the preoperative Karnofsky Performance Scale (KPS) and American Society of Anesthesiologists (ASA) scores on perioperative complications in patients with recurrent glioma who underwent tumor resection via craniotomy.
A total of 96 patients were retrospectively reviewed. Based on KPS and ASA scores, patients were categorized into high KPS (> 70) or low KPS (≤ 70) and high ASA (3~4) or low ASA (1~2) groups. Differences in intraoperative risk factors and perioperative complications among the groups were analyzed. Multivariate analysis was performed to identify risk factors for perioperative complications.
The most frequent perioperative complications were cerebrospinal fluid leakage (31.8%) and intracranial infection (27.0%); 30-day mortality was 5.2%. The incidence rates of severe complications, central nervous system complications, and total complications were comparable in the low and high KPS groups and in the low and high ASA groups (all p > 0.05). Multivariate analysis showed that low KPS and high ASA scores were not the independent risk factors for perioperative complications.
Low KPS and high ASA scores are not associated with increased postoperative complications in patients with recurrent glioma who undergo tumor resection via craniotomy.
About 0.5% of the US population (1.7 million) is living with a lost limb and this number is expected to double by 2050. This number is much higher in other parts of the world. Within days to weeks of an extremity amputation, up to 80% of these individuals develop neuropathic pain presenting as phantom limb pain (PLP). The level of PLP increases significantly by one year and remains chronic and severe for about 10% of individuals. PLP has a serious negative impact on individuals’ lives. Current pain treatment therapies, such pharmacological approaches provide limited to no pain relief, some other techniques applied to the central nervous system (CNS) and peripheral nervous system (PNS) reduce or block PLP, but none produces long-term pain suppression. Therefore, new drugs or novel analgesic methods must be developed that prevent PLP from developing, or if it develops, to reduce the level of pain. This paper examines the potential causes of PLP, and present techniques used to prevent the development of PLP, or if it develops, to reduce the level of pain. Finally it presents a novel technique being developed that eliminates/reduces chronic neuropathic pain and which may induce the long-term reduction/elimination of PLP.
The present study aimed to assess the clinical effects of ultrashort wave therapy combined with acupuncture and rehabilitation training on patients with dysphagia after stroke.
A total of 126 patients with stroke with dysphagia were randomly divided into an acupuncture group (control group: 63 patients) and a comprehensive rehabilitation training group (treatment group: 63 patients). The control group received rehabilitation training and acupuncture, whereas the treatment group received ultrashort wave therapy in addition to rehabilitation training and acupuncture (comprehensive rehabilitation training). The curative effect was evaluated using water-drinking test scores and swallowing quality of life scale (SWAL-QOL) scores before and after intervention. Additionally, the incidence of aspiration pneumonia was assessed in the two groups.
The water-drinking test scores in both groups were significantly better after 4 weeks of intervention than before intervention (P < 0.01); however, the improvement degree was significantly greater in the treatment group than in the control group (P < 0.01). The SWAL-QOL scores in both groups were significantly higher after intervention than before intervention (P < 0.05); however, the improvement degree was significantly greater in the treatment group than in the control group (P < 0.05). Moreover, the incidence of aspiration pneumonia was significantly lower in the treatment group than in the control group (P < 0.05).
Comprehensive rehabilitation training can greatly improve dysphagia after stroke and can effectively reduce the incidence of aspiration pneumonia.
This study applied a steady-state visual evoked potential (SSVEP) based brain–computer interface (BCI) to a patient in lock-in state with amyotrophic lateral sclerosis (ALS) and validated its feasibility for communication. The developed calibration-free and asynchronous spelling system provided a natural and efficient communication experience for the patient, achieving a maximum free-spelling accuracy above 90% and an information transfer rate of over 22.203 bits/min. A set of standard frequency scanning and task spelling data were also acquired to evaluate the patient’s SSVEP response and to facilitate further personalized BCI design. The results demonstrated that the proposed SSVEP-based BCI system was practical and efficient enough to provide daily life communication for ALS patients.
There have been many clinical studies or trials for patients with ischemic stroke by cell therapy, which includes olfactory ensheathing cell (OEC), mononuclear cell, mesenchymal stromal cell, fetal neural cell or products of varying stem cells, etc. Those cells through different transplanting ways have showed moderate neurorestorative effect in patients with ischemic stroke, but majority were not multicenter randomized, double-blinded, placebo-controlled studies or trials. OEC transplantation has shown a more effective to restore neurological damage in central nervous system (CNS). We hypothesize that OEC through intra-olfactory mucosa transplantation can migrate into the ischemic stroke area around and restore neurological deficit caused from this disaster.
This is a multicenter, randomized, double-blinded, placebo- controlled 12 month clinical study of OECs and Schwann cells (SCs) for patients with sub-acute ischemic stroke and chronic ischemic stroke, to test which kind of cell has more neurorestorative effect for patients with ischemic stroke relative to placebo.
This study is involved two groups of patients with sub-acute ischemic stroke and chronic ischemic stroke. Each group enrolls 30 patients. The experimental intervention consists in using OECs and SCs through intra-olfactory mucosa transplantation in participating patients. This will be compared with using placebo (injecting cell culture medium). Participating patients in groups of sub-acute ischemic stroke and chronic ischemic stroke are randomized in natural order to divide into A, B, or C groups and get one of experimental treatment procedures. Patients, operating physicians, and assessing physicians are left unaware of what cells or medium will be injected to participating patients. All patients will be assessed before treatment and after one month, three months, six months, and one year.
The clinical study protocol and consent form were approved by Chinese Association of Neurorestoratology and the ethics committees of the hospitals which joined this clinical study. Findings will be published in peer-reviewed journals.
In this mini-review, we illustrate the brain network oscillations in different brain areas, including the medial septal diagonal band complex (MSDB) and hippocampus, especially at gamma frequency bands (γ, 30–80 Hz) and theta frequency bands (θ, 4–12 Hz), and their induction and modulation by physical stimulation, such as light and sound, and pharmacological stimulation with agents such as agonists of the kainite subunit ionotropic glutamate receptor, metabotropic glutamate receptor, metabotropic cholinergic receptor, and nicotinic cholinergic receptor. Recent findings demonstrate that boosting gamma oscillations in specific brain areas appears to be able to restore cognitive function and reduce relative pathology in neurodegenerative diseases, such as Alzheimer’s disease. Thus, exploration of strategies to enhance or restore impaired gamma oscillations may be a new and effective method to improve the conditions in these devastating diseases.
Trace element and its probable role in biological systems have attracted the attention of many researchers in recent years. Previous work has shown that ZnTe administered in drinking water to pregnant rats during pregnancy, delivery, lactation and offspring maturation up to prepuberal stage is able to modify several parameters of spontaneous behaviours related to cognition in offspring rats. Since Zn and Te have many biological properties, it’s not possible to conclude if behavioural changes are due to Zn, Te or both trace elements activity. In the present work, K2TeO3 and ZnCl2 were used alone in order to evaluate single actions of trace elements. Four experimental groups were formed: Control (water), Zn-treated group, Te-treated groups, and Zn+Te group. At the end of the experiments at 30 days of age offspring of each group were tested individually in a Double-Hole Board Labyrinth to evaluate lateralized exploration. Open field enriched with a rack and hole-board to evaluate motivated exploration; single cage in an intruder-host test to evaluate social interaction, and forced swimming cylinder to evaluate the survival responses. Results showed selective changes in rearing for Te (first Test); blocking of the natural left-biased exploration (second Test) increased time to confront the intruder with decreased time to interact with the intruder (third Test), and decreased time to active swimming (fourth Test).
With the exception of duration of the social interaction, Zn has no effect. Results suggest that most of the behavioural changes found with ZnTe in previous studies are due to Te.
To explore the therapeutic effects of melatonin by two different routes, by caudal vein and intraperitoneal injection, on cerebral ischemia-reperfusion (IR) injury in adult rats.
60 Sprague-Dawley rats were randomly divided into normal control (CON), middle cerebral artery occlusion (MCAO), intraperitoneal and caudal vein injection groups. Nissl and immunohistochemical staining were used to observe the morphological and quantitative changes of neurons and the expression of cleaved Caspase-3, Fas and FasL proteins in the injured cerebral cortex.
More Nissl-stained and NeuN+ cells were observed in both the intraperitoneal and caudal vein injection groups as compared with the MCAO group (P < 0.05), and the number of Nissl-stained and NeuN+ cells in caudal vein injection group was significantly higher than in intraperitoneal injection group at each time point (all P < 0.05). There were fewer cleaved Caspase-3+, Fas+ and FasL+ cells in both intraperitoneal and caudal vein injection groups than that in MCAO group 24 hours and 72 hours after IR (all P < 0.05). Meanwhile, there were significantly fewer cleaved Caspase-3+, Fas+ and FasL+ cells in caudal vein injection group than in intraperitoneal group (all P < 0.05).
Melatonin therapy by both intraperitoneal and caudal vein injection could alleviate the expression of cleaved Caspase-3, Fas and FasL proteins in the cerebral cortex in rats after cerebral ischemia reperfusion and protect the neurons from injury, and had neuroprotective effects, and the therapeutic effect by caudal vein injection was better than by intraperitoneal injection.
The Neurorestoratology discipline is getting worldwide attention from the clinicians, basic scientists, students and policy makers alike. Accordingly, this year too, the discipline has made profound advances and great achievements for the benefit of the mankind. In this report, of the 2018 Neurorestoratology Yearbook, salient features of new developments are summarized. This Yearbook consists 3 key themes namely (i) the new findings on pathogenesis of neurological diseases or degeneration; (ii) the new mechanisms of neurorestorative aspects; and (iii) the achievements and progresses made in the clinical field of neurorestorative therapies. The new trend has emerged in clinical studies that are based on greater levels of evidence-based medical practices both in clinical therapies and clinical trials based on standard designs.
A 46-year-old female patient experienced severe pain in both lower limbs following a traffic accident in 2008. The pain mainly presented in her feet; she also experienced sensory impairment, convulsions, and exercise function disorders. She was diagnosed with neuropathic pain, and no medicine had any remarkable effect. Therefore, spinal cord stimulation (SCS) was performed in October 2019. Her pain did not reduce after the initial adoption of conventional SCS until the application of high frequency SCS (HF-SCS). At the 6-month follow-up, the pain in her lower limbs was considerably reduced, lower limb motor function was slightly improved, and muscle twitching in both feet disappeared.
In 2016 we published the first Yearbook of Neurorestoratology, which summarized pathogenesis in nervous system disease and damage, as well as neurorestorative mechanisms and neurorestorative therapeutic results. Given the progress and achievements occurring in 2017, we have put together those major progresses as the “2017 Yearbook of Neurorestoratology”, which can help readers to easily follow the latest developments in Neurorestoratology.
To evaluate the functional outcome of foot and ankle deformity secondary to spinal bifida treated by various methods.
A retrospective analysis of 248 patients with foot and ankle deformity secondary to spina bifida with an average age of 25.5 years and underwent surgical treatment in our hospital from March 2012 to April 2016. The deformity correction was achieved by various methods like soft tissue procedure, bony procedure combined with external fixator application. All the patients were followed up at regular interval. Post operative rehabilitation and protective splints were provided after fixator removal. The final outcome was evaluated with American Orthopedic Foot and Ankle Society (AOFAS) score and Qin’s criteria for deformity correction, matched T-test was used to compare the data pre and post surgery.
According to the short term follow up, all these patients were achieved complete correction and able to achieve full weight bearing. Out of 248 patients, 13 patients were lost follow up. 235 patients were followed up for an average of 28.5 months. We noted various minor complications like superficial pin tract infection was seen in 5, pin breakage in 4, pin tract burn injury in 1, and recurrence of deformity was noted in 20 patients especially in children, anterior dislocation of the tibiotalar joint in 3 patients with severe clubfoot deformity. At the final follow up, the mean AOFAS score increased to 88.7, with a significant improvement compared with the score before surgery (P < 0.05). Based on Qin’s criteria for deformity correction, the outcome was graded as excellent in 180 patients, good in 55, and fair in none of the cases.
Through orthopaedic treatment, combination of soft tissue and bony procedures along with external fixator helps to achieve complete correction of deformity, healing of ulcer, restoration of functional activity for spinal bifida sequelae patients.
We assessed the safety and clinical effectiveness of intranasal therapy with M2 macrophage-derived soluble products (M2-SPs) for treating patients with cerebrovascular disease (CVD).
The protocol of the study was registered at www.ClinicalTrails.gov (NCT02957123). The study group comprised 30 patients with chronic CVD. Neurological status was examined before therapy and at 1- and 6-month follow–up. Concentrations of 32 cytokines in the blood serum were evaluated before and 1 month after therapy onset. Neurological assessment was conducted with the following scales: Subjective Assessment of Clinical (neurological) Symptoms (SACS), Hospital Anxiety and Depression Scale (HADS), Functional Mobility Assessment in Eldery Patients (FMA), and Montreal Cognitive Assessment (MoCa).
M2-SPs treatment (once daily for 28~30 days) was found to be safe and well tolerated. Neuropsychological improvements showed the amelioration of neurological symptoms, reduction in anxiety and depression levels, improvement in balance and gait ability as well as cognitive functions. Clinical effects could be detected at the end of treatment course and was stable during 6-month follow-up. Blood serum cytokine evaluation demonstrated diminished baseline levels of many cytokines including those with neurotrophic activity (brain-derived neurotrophic factor, BDNF; hepatocyte growth factor, HGF; migration inhibitory factor, MIF). Upon treatment, most pronounced clinical responses were observed in patients with most severe cytokine deficiency and post-therapy normalization of MIF and HGF levels.
Intranasal therapy with M2-SPs is safe and according to preliminary data reduces neuropsychological deficit in patients with chronic CVD. The positive effect of M2-SPs treatment seems to be HGF- and MIF-dependent.
Neural damage has been a great challenge to the medical field for a very long time. The emergence of brain-computer interfaces (BCIs) offered a new possibility to enhance the activity of daily living and provide a new formation of entertainment for those with disabilities. Intracortical BCIs, which require the implantation of microelectrodes, can receive neuronal signals with a high spatial and temporal resolution from the individual’s cortex. When BCI decoded cortical signals and mapped them to external devices, it displayed the ability not only to replace part of the human motor function but also to help individuals restore certain neurological functions. In this review, we focus on human intracortical BCI research using microelectrode arrays and summarize the main directions and the latest results in this field. In general, we found that intracortical BCI research based on motor neuroprosthetics and functional electrical stimulation have already achieved some simple functional replacement and treatment of motor function. Pioneering work in the posterior parietal cortex has given us a glimpse of the potential that intracortical BCIs have to control external devices and receive various sensory information.
The 10th annual conference of the International Association of Neurorestoratology (IANR) was held on Sept. 28-30, 2017. Here main promising topics were summarized, such as, memorial of Professor Geoffrey Raisman—Life Honorary President of IANR, highlights which include cell transplantation, new mechanism and new technology, problems and challenges in the field of Neurorestoratology.
Repair and regeneration of the injured peripheral nerve (PN) is a challenging issue in clinics. Although the regeneration outcome of large PN defects is currently unsatisfactory, recently, the study of PN repair has considerably progressed. In particular, biomaterials for repairing PNs, such as nerve guidance conduits and nerve repair membranes, have been well developed. Herein, we summarize the anatomy of the PN, the pathophysiological features of the nerve injury, and the repair process post injury. Then, we highlight the progress in the development of natural and synthetic biomaterials and summarize the applications, advantages, and disadvantages of these materials. These materials can be used as nerve repair membranes and nerve conduits in the field of PN repair. Finally, we discuss the challenges encountered and development strategies for PN repair in the future.
Post-stroke depression (PSD) is a frequent neuropsychiatric disorder following stroke which is associated with poor outcome. Neuronal Per-Arnt-Sim (PAS) domain protein 4 (Npas4) is associated with cognitive function. Npas4 expression in peripheral blood mononuclear cells (PBMCs) from patients with PSD was measured to find new therapeutic strategy.
Ischemic stroke patients (n = 152) within 1 week of stroke onset were recruited. At 3 months follow-up, the patients were divided into a PSD group (n = 77) and a stroke group (n = 75) using the Hamilton Rating Scale. Healthy subjects (n = 75) were also recruited in the study. The PSD group received 12 weeks of duloxetine treatment. Cognitive function was evaluated using the P300 test. Npas4 expression in PBMCs was measured by quantitative RT-PCR (qPCR).
Before treatment, P300 latencies in the PSD group were prolonged and the P300 amplitudes were lower than the control group (P < 0.01). Npas4 expression in the PSD group was also lower than the control group (P < 0.01). After treatment, the P300 latencies were reduced and the amplitudes were significantly elevated in the PSD group compared to that before treatment (P < 0.01). Meanwhile, Npas4 levels were significantly higher than that before treatment (P < 0.01). Npas4 expression was positively correlated to the P300 amplitudes (P < 0.05).
Changes of Npas4 expression in PBMCs are associated with cognitive impairment in PSD patients and new therapeutic options applying Npas4-related transcript mechanism could be considered in the future.
Time is infinite movement in constant motion. We are glad to see that Neurorestoratology, a new discipline, has grown into a rich field involving many global researchers in recent years. In this 2019 yearbook of Neurorestoratology, we introduce the most recent advances and achievements in this field, including findings on the pathogenesis of neurological diseases, neurorestorative mechanisms, and clinical therapeutic achievements globally. Many patients have benefited from treatments involving cell therapies, neurostimulation/neuromodulation, brain–computer interface, neurorestorative surgery or pharmacy, and many others. Clinical physicians can refer to this yearbook with the latest knowledge and apply it to clinical practice.
The retrospective study summarizes 28 years of cell therapy for neurotrauma of different origin. The four experimental groups were the groups of neurotrama that included traumatic disease of the spinal cord, traumatic disease of the brain and chronic vegetative post-traumatic state. The first group received transplantations of the fetal cells of neural tissue. The second group received the tissue engineering surgery with the transplantation of the fetal cells of neural tissue. The third group were the cases of the bioengineering pasty of the damaged brain tissue; and fourth were the cases of neurotrauma that were treated with the transplantation of the hematopoietic stem cells (HSCs) and hematopoietic precursor cells (HPCs). The long-term follow up proved the cell therapy with HSCs and HPCs to be the safest and most effective.
Current treatments for B cell-mediated disease are mainly based on global B cell depletion, thereby eliminating pathogenic B cells as well as Breg subsets. A more refined modulation of B cell activity could prove beneficial for patient treatment.
To investigate the immunomodulatory function of human amniotic fluid stromal cells (hAFSCs) on different subpopulation of B lymphocytes.
hAFSCs were isolated and cultured and identified by characteristic phenotypic markers. After coculture of B lymphocytes with hAFSCs, the activation, proliferation, differentiation, as well as apoptosis, cell cycle, and expression of the inhibitory costimulatory molecules B7H1, B7H3, and B7H4 of B lymphocytes were examined in vitro.
Coculture with hAFSCs significantly decreased the expression of CD80/CD86, Ki-67 and CFSE expression, on activated B lymphocytes. These might be due to the inhibition of B lymphocyte apoptosis and cell cycle arrest. In activated B lymphocytes, coculture with hAFSCs resulted in a reduced proportion of memory B and plasma cells, reduced amounts of immunoglobulins. hAFSCs could balance the B1 to B2 cell subpopulation ratio. hAFSCs could inhibit the expression of the negative co-inhibitory molecule B7H4 and PD-L1 on the activated B lymphocytes.
hAFSCs could inhibit B cell activation, proliferation, and subpopulation differentiation. These might be due to their affect on B cell apoptosis, cell cycle and the expression of costimulatory molecules of human B lymphocytes. Our experiment provided the evidence for hAFSCs as ideal seed cells with therapeutic potential for treating humoral immunity disorders, which were mainly mediated by B lymphocytes.
To introduce a novel intradural microsurgery method for acute spinal cord injury, while evaluating the safety and effect.
87 patients with complete spinal cord injury were enrolled and treated with the novel intradural microsurgery within 48 h, in addition to traditional surgical interventions (internal fixation, laminectomy).
Complications including massive hemorrhage, infection and impairment aggravation did not occur during and after surgery. There were 16 cases of B grade, 13 cases of C grade, 6 cases of D grade base on the ASIA impairment scale 3 months after surgery, and average 18.51 increase in motor score, 16.64 increase in light touch score, 17.12 increase in pin prick score were achieved.
Early intradural microsurgery is safe, causing no neurological function lost and no major adverse event, and it is associated with neurologic improvement in patients with severe spinal cord injury.
Clinical cell therapies (CTs) for neurological diseases and cellular damage have been explored for more than 2 decades. According to the United States Food and Drug Administration, there are 2 types of cell categories for therapy, namely stem cell-derived CT products and mature/functionally differentiated cell-derived CT products. However, regardless of the type of CT used, the majority of reports of clinical CTs from either small sample sizes based on single-center phase 1 or 2 unblinded trials or retrospective clinical studies showed effects on neurological improvement and the ability to either partially or temporarily thwart the deteriorating cellular processes of the neurodegenerative diseases. There have been only a few prospective, multicenter, randomized, double- blind placebo-control clinical trials of CTs so far in this developing novel area that have shown negative results, and more clinical trials are needed. This will expand our knowledge in exploring the type of cells that yield promising results and restore damaged neurological structure and functions of the central nervous system based on higher level evidence-based medical data. In this review, we briefly introduce the developmental process, current state, and future prospective for clinical neurorestorative CT.
Olfactory ensheathing cells (OECs) have shown promising results for patients with neurologic diseases in non-double-blind, placebo control studies. Thirty patients with a unilateral ischemic stroke of more than a year were enrolled in a phase 2, multicenter, randomized, double-blind, and placebo-controlled cell therapy trial with a subsequent 12-month follow-up. The primary therapeutic objective has shown that after 12 months, there were significant differences in National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) assessment scores among the OEC group, Schwann cell group and placebo medium group at one-year follow-up. The second therapeutic objective found that there were significant differences in NIHSS, mRS, and BI assessment scores when comparing the endpoint data with the baseline data in the OEC group. There was neither hypersensitivity reaction nor adverse event. The results of this multicenter, randomized, double-blind, and placebo-controlled study indicate that injecting OECs into the olfactory sub-mucosa have neurorestorative effects, which can improve the quality of life for patients with chronic ischemic strokes without serious side effects.
Vagus nerve stimulation (VNS) has recently been used in neurorehabilitation and the recovery of consciousness based on its effects on cortical plasticity. The aim of this study was to examine the therapeutic effects of VNS on patients with a minimally conscious state (MCS).
All patients included in the study were assessed more than 5 months after injury and were receiving regular rehabilitation at our hospital from August 2018 to October 2019. Ten patients diagnosed with MCS by Coma Recovery Scale-Revised (CRS-R) test who underwent VNS surgery were enrolled. The scores on CRS-R evaluation at baseline (before VNS implantation) and 1, 3, and 6 months after VNS treatment were recorded. The stimulation parameters were chosen according to a previous study. All clinical rehabilitation protocols remained unchanged during the study. Furthermore, safety was assessed by analyzing treatment-emergent adverse events (TEAEs).
No significant improvement in the total CRS-R scores at the end of the 1-month follow-up was observed (p > 0.05). After 3 months of stimulation, a significant difference (p = 0.0078) was observed in the total CRS-R scores compared with the baseline. After 6 months of VNS treatment, CRS-R assessments showed a continuous significant improvement (p = 0.0039); one patient emerged from the MCS and recovered functional communication and object use. Interestingly, one item of CRS-R scores on visual domain was sensitive to VNS treatment (p = 0.0039). Furthermore, no serious adverse event occurred throughout the study.
This exploratory study provides preliminary evidence suggesting that VNS is a safe and effective tool for consciousness recovery in patients with MCS.
A number of clinical trials of olfactory ensheathing cells (OECs) for the treatment of chronic spinal cord injury (SCI) have been carried out all over the world. However, their safety and efficacy have not been basically evaluated. Moreover, there are no uniform standards laid out for the use of optimal source, transplantation method and the dosage of OECs.
This study evaluated the source, dose, and route of transplantation of OECs for the treatment of chronic SCI.
PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang Data were searched for the clinical studies of OECs in the treatment of chronic SCI on July 2018.
A total of 30 articles on OECs transplantation for chronic SCI were selected for comprehensive evaluation of OECs sources, doses, and transplantation methods. The efficacy of OECs in the treatment of chronic SCI was evaluated using Review Manager 5.3.
Fetal OECs are the primary source of cells for the treatment of chronic SCI in OECs, with standardized cell-culture and quality-control processes. Fetal OECs can significantly improve the neurological function of patients with chronic SCI. It is an ideal cell therapy for neurorestoration. However to explore more precise and minimally invasive treatment options are required in the future.
Deep brain stimulation surgery has been performed in various movement disorders and psychiatric diseases. However, electrical stimulation may unexpectedly affect other types of adjacent neurons outside of the target area. Recently, optogenetics has provided the opportunity to modulate specific target neurons. Since this novel technique can individually control specific neurons in freely moving animals, it could be proposed to restore neural circuit function to related diseases, such as affective disorders, Huntington’s disease (HD), and Parkinson’s disease (PD). Herein, we discuss how optogenetics works as a treatment for Parkinson’s disease and other neural circuit dysfunctions.