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.
Mesenchymal stromal cells (MSCs) including mesenchymal stem cells to potentially differentiate into different tissue lineages widely exist in various tissues. In recent years, the clinical research and application of MSCs have become more extensive, but no standardized guidelines for the preparation and quality control of clinical-grade MSCs currently exist. To standardize the preparation and quality control of MSCs using the human umbilical cord, placenta, bone marrow, and adipose tissue as sample sources for the Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) member units, this standard is formulated following the T11/CSSCR 001-2017 General Requirements for Stem Cells, Good Manufacturing Practice Pharmaceutical Products (2010 Edition), Pharmacopoeia of the People's Republic of China (2015 Edition), Guiding Principles for Quality Control of Stem Cell Preparations and Preclinical Research (Trial), Code for Cell Banking Facility Quality Management, Sterile Drug Appendix to Pharmaceutical Production Quality Management Regulations, GMP Appendix — Cell Therapy Products (Draft for Comment), The International Society for Cellular Therapy position statement (2006), and Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Moreover, this standard includes donor evaluation, sample collection, cell preparation, cell inspection, packaging, labeling, transportation and storage, and quality control. It represents the minimum requirements for clinical-grade mesenchymal stromal cell culture and quality control. Moreover, it will be further optimized following the progress of preclinical and clinical research.
Brainstem hemorrhage (mainly pontine hemorrhage caused by hypertension) has the clinical characteristics of acute onset, rapid progress, high mortality, and high disability rate. Due to the complexity of the brainstem’s anatomical structure and functional importance, it is generally recognized that brainstem treatment is difficult and risky, so it has been regarded as a restricted area of surgery. However, in recent years, continuous progress is being made in many areas, including microsurgical technology, stereotactic technology, robot-assisted surgery, neuroendoscopy, and theoretical and clinical practice of neurorestoration, aiding in the understanding, diagnosis, and treatment of brainstem hemorrhage injuries. The Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) organized relevant experts to formulate this clinical guideline to diagnose and restore damaged nerves after brainstem hemorrhages, promote a standardized diagnosis, and neurorestoratologically treat this disease.
Stroke is the main cause of death and disability among Chinese, and neurorestoration is an effective therapeutic strategy for patients with stroke. In recent years, many achievements have been made in stroke neurorestoration, but viewpoints for managing stroke vary per discipline. In order to promote standardization of diagnosis and treatment for stroke neurorestoration, the Chinese Association of Neurorestoratology (CANR; Preparatory) and China Committee of International Association of Neurorestoratology (IANR-China Committee) organized professional experts in the field to integrate fragmented neurorestorative methods and establish clinical diagnostic and therapeutic guidelines for stroke neurorestoration. This guideline includes the diagnosis and staging of stroke and therapeutic recommendations for neurorestoration at different stages of stroke in order to improve survival and quality of life of stroke patients.
Currently, there are many different standards for the quality control of olfactory ensheathing cell (OEC) culture prepared from human olfactory bulb and mucosa. It is challenging to compare the clinical results of OEC treatment from different hospitals. Based on various standards, the Chinese Association of Neurorestoratology (CANR; Preparatory) and China Committee of International Association of Neurorestoratology (IANR-China Committee) organized professional experts in this field to evaluate the data and develop a standard for clinical applications, including donor evaluation, sample collection, cell culture, cell testing, packaging labels, storage, transportation, and quality control of intermediate/finished cell products, as well as training and management procedures for laboratory operators, the use and management of materials and equipment, and routine maintenance of a clean environment. These standards apply to the quality and control of OEC culture using human olfactory bulb and mucosa as the sample source for the member units of the CANR (Preparatory) and IANR-China Committee. It serves as a reference for physicians around the world who perform OEC clinical applications. This standard represents the minimum required standards for quality control when performing clinical-grade OEC cultures in clinical neurorestorative treatments.
Treatment of spinal cord injury (SCI) remains challenging. Considering the rapid developments in neurorestorative therapies for SCI, we have revised and updated the Clinical Therapeutic Guidelines for Neurorestoration in Spinal Cord Injury (2016 Chinese version) of the Chinese Association of Neurorestoratology (Preparatory) and China Committee of International Association of Neurorestoratology. Treatment of SCI is a systematic multimodal process that aims to improve survival and restore neurological function. These guidelines cover real-world comprehensive neurorestorative management of acute, subacute, and chronic SCI and include assessment and diagnosis, pre-hospital first aid, treatment, rehabilitation, and complication management.
To investigate the clinical effects of time window on hyperbaric oxygen treatment (HBOT) in patients with disorders of consciousness (DOC).
All the clinical research literature regarding HBOT for DOC published between January 2000 and November 2020 were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Standards Database (WFSD) and VIP Database using Chinese key words disorders of consciousness, the vegetable state, minimally conscious state, or hyperbaric oxygen followed by a comprehensive meta-analysis.
The query gave rise to 348 results, in which 21 articles were eventually selected for meta-analysis. Among the selected 21 articles, 18 articles involved a time window comparison. All the patients were classified into < 60- (718 patients) and ≥ 60- (374 patients) day groups depending on the number of days from HBOT initiation. The Jadad scores for the included datasets were relatively low in general with 2 points as the highest score. Comparable baseline data were demonstrated in all of the articles. Datasets from different sources were pooled and analyzed, and the results suggested that the clinical curative effect rate in the treatment group was significantly higher compared with that in the control group (curative effect rate: 69.86% versus 42.30%; Z = 11.28, P = 0.000, odds ratio = 3.80, 95% CI = 3.02-4.80). Additionally, the adverse reaction rate of the < 60-day group was found to be significantly lower compared with that of the ≥ 60-day group (Z = 10.01, P = 0.000, odds ratio = 4.82, 95% CI = 3.54-6.56). The funnel diagram in articles related to curative effect analysis and time window evaluation is inverted and symmetrical, indicating that publication bias was not significant.
The clinical curative effect of the HBOT group is higher compared with that of the control group. However, the conclusions based on meta-analysis are limited because of the methodological problems of some studies. Therefore, the clinical efficacy needs to be further tested using carefully designed large sample trials (multicenter, randomized, controlled, and double-blind).
Our purpose was to investigate the cytomegalovirus expression in patients with Rasmussen's encephalitis (RE) and to analyze the correlation between cytomegalovirus expression and the alteration of cognition.
The expression of human cytomegalovirus (HCMV) in resected brain tissue from 36 children with RE was analyzed and the impact of cytomegalovirus infection on the cognitive function of patients was evaluated. The primary outcome was change in score from baseline to month 24 on the Wechsler Intelligence Scale for Children (WISC-IV). All children were evaluated preoperatively and postoperatively according to the WISC-IV using factors such as verbal comprehension index, perception reasoning index, working memory index, processing speed index, and the full scale intelligence quotient.
Children with RE had different degrees of intellectual disability. The age at onset and duration of epilepsy have a close relationship with patients' IQ. There exists a direct correlation between HCMV expression and postoperative cognitive status. Patients' cognitive behavior in HCMV positive group improved significantly after hemispherectomy compared with negative group.
We noted a positive correlation between the quantity of expression of cytomegalovirus and improvement of cognition after surgery. Therefore, the expression of cytomegalovirus could predict prognosis for cognitive rehabilitation and remove this risk factor through the hemisphere procedure could be beneficial to long-term cognitive remodeling.
Induced pluripotent stem cells (iPSCs) have become the leading research object in the clinical application of restorative medicine. They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues. To date, the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results, with great potential in cell drug development. However, because of some unique biological properties and differences from traditional drug production processes, cell drug research and development has many problems that can hinder clinical applications. Given this situation, the Chinese Association of Neurorestoratology (Preparatory) and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here. Overall, the aim was to promote the clinical application of neural stem cells (NSCs) and their further derived neural cells from iPSC sources and promote cell drugs’ production and development. This standard refers to the latest research results, quality evaluation criteria for traditional medicines, and the regulatory framework for cellular treatments. The standard considers general biological properties of cells, including cell morphology, cell cycle, karyotype, and cell viability. The specific biological properties of NSCs, such as cell surface markers and differentiation ability, general drug standards, such as aseptic testing, endotoxins, human virus detection, and cell-related drug standards, such as telomerase activity and tumorigenicity, are also considered. This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.
COVID-19 has been an emerging and rapidly evolving risk to people of the world in 2020. Facing this dangerous situation, many colleagues in Neurorestoratology did their best to avoid infection if themselves and their patients, and continued their work in the research areas described in the 2020 Yearbook of Neurorestoratology. Neurorestorative achievements and progress during 2020 includes recent findings on the pathogenesis of neurological diseases, neurorestorative mechanisms and clinical therapeutic achievements. Therapeutic progress during this year included advances in cell therapies, neurostimulation/neuromodulation, brain-computer interface (BCI), and pharmaceutical neurorestorative therapies, which improved neurological functions and quality of life for patients. Four clinical guidelines or standards of Neurorestoratology were published in 2020. Milestone examples include: 1) a multicenter randomized, double-blind, placebo-controlled study of olfactory ensheathing cell treatment of chronic stroke showed functional improvements; 2) patients after transhumeral amputation experienced increased sensory acuity and had improved effectiveness in work and other activities of daily life using a prosthesis; 3) a patient with amyotrophic lateral sclerosis used a steady-state visual evoked potential (SSVEP)-based BCI to achieve accurate and speedy computer input; 4) a patient with complete chronic spinal cord injury recovered both motor function and touch sensation with a BCI and restored ability to detect objects by touch and several sensorimotor functions. We hope these achievements motivate and encourage other scientists and physicians to increase neurorestorative research and its therapeutic applications.
Chronic disorders of consciousness (DOC) include the vegetative state and the minimally consciousness state. The DOC diagnosis mainly relies on the evaluation of clinical behavioral scales, electrophysiological testing, and neuroimaging examinations. No specifically effective neurorestorative methods for chronic DOC currently exist. Any valuable exploration therapies of being able to repair functions and/or structures in the consciousness loop (e.g., drugs, hyperbaric medicines, noninvasive neurostimulation, sensory and environmental stimulation, invasive neuromodulation therapy, and cell transplantation) may become effective neurorestorative strategies for chronic DOC. In the viewpoint of Neurorestoratology, this guideline proposes the diagnostic and neurorestorative therapeutic suggestions and future exploration direction for this disease following the review of the existing treatment exploration achievements for chronic DOC.
Spasticity after brain injury is a neurological sequela caused by damage to upper motor neurons. The primary symptoms are involuntary muscle activity, decreased muscle strength, and joint contracture. Acupuncture as a therapeutic method to regulate central nervous system function has been studied widely in recent years. Many clinical experiments have proved that acupuncture has positive effects on spasticity after brain injury. In this review, we discuss recent research of acupuncture treatment and the need for large randomized controlled trials.
In studies from this laboratory, the chronic administration of ZnTe during pregnancy, lactation, and prepuberal stages of litter (F1 generation) modified the behavioral patterns of motivated exploration, lateralized exploration, social activity, and survival responses of maturing rats. To determine whether these affected behaviors would extend to the next generation, F1 litter rats previously exposed to tellurium (Te) up to 30-day-old were left at rest with no further treatment up to 90-day-old. Then, F1 female rats were mated with normal untreated male rats, and in the next generation (F2), the litter rats at 30-day-old preserved the modified behaviors previously observed in their parents. The study revealed that Te effects were intergenerational. Here, considering that ZnTe was used in the previous study and that Zn ion has many physiological functions in the cell, experiments were conducted to elucidate if Zn would have an intergenerational effect similar to Te. Working with the same experimental setup as in the previous study but using ZnCl2 instead of ZnTe, results revealed that none of the behavioral responses studied were affected by the F1 generation. However, in the F2 generation, lateralized exploration and survival behavior were inhibited, suggesting that Zn also has an intergenerational effect.