30 years of American Society for Neural Therapy and Repair (ASNTR): A personal perspective at the intersection of science, politics, and culture.

The American Society for Neural Therapy and Repair (ASNTR) started 30 years ago in 1993 as the American Society for Neural Transplantation (ASNT), with an emphasis on neural transplantation. Through the years, the Society has been shaped as much by our expanding knowledge of neurodegenerative disorders and how to treat them as it has by politics and culture. What once felt like a leash on neuroscience research, has turned into an advantage as neural transplantation evolved into Neural Therapy and Repair. As a Co-Founder this brief commentary provides a personalized account of our research during the Society's years.

Biological Basis of Invigorating Qi and Activating Blood Cirulation in Regulating Neural Repair After Ischemic Stroke： A Review / 中国实验方剂学杂志

Stroke is the leading cause of death and disability. Therefore， it is critical to develop the approaches for improving recovery and neural repair after stroke. Recovery after stroke involves complex interrelated systems of neural repair. The whole process of neural repair requires a series of coordinated interactions， such as response of neuronal cell body to traumatic stimuli， neural stem cell proliferation and migration， axoplasmic transport of signaling molecules， construction of cytoskeleton， and formation of axonal growth cone， to achieve regeneration and growth. As a potential new target for the treatment of neurologic defects， neural remodeling has important research significance in both the specific mechanism of neural repair and the clinical treatment of neurologic defects. After brain injury， single therapy is often ineffective due to the complex mechanism of internal repair， and thus comprehensive therapy becomes the development direction to improve the brain repair. Invigorating qi and promoting blood can promote nerve function remodeling after injury through neural protection， angiogenesis， neurogenesis， loop reconstruction， and cytokine regulation， playing a key role in nerve repair after stroke. Its mechanism is associated with autophagy， immunomodulation， and microRNA regulation， which fully embodies the multi-pathway， multi-target， and overall regulation characteristics of invigorating Qi and activating blood. Therefore， it is of theoretical and guiding significance to study the brain function rehabilitation after stroke by invigorating qi and activating blood.

Effect and Mechanism of Qixian Tongluo Prescription on Neural Function Recovery in Patients with Cerebral Infarction / 中国实验方剂学杂志

Objective:To investigate the effect of Qixian Tongluo prescription on neural function recovery in patients with cerebral infarction and its mechanism. Method:A total of 100 inpatients （January to June，2020）with cerebral infarction in the Neurology Department of Wenzhou Hospital of Traditional Chinese Medicine were assigned to an experimental group （<italic>n</italic>=50） and a control group （<italic>n</italic>=50） according to the random number table. Both groups received conventional treatment of western medicine，while the experimental group took additional Qixian Tongluo prescription. Treatment lasted for 12 weeks. The clinical efficacy，National Institutes of Health Stroke Scale （NIHSS） score， the modified Barthel index （MBI），Fugl-Meyer assessment （FMA） score， and levels of brain-derived neurotrophic factor（BDNF），vascular endothelial growth factor（VEGF）， and stromal cell-derived factor-1（SDF-1） in peripheral blood of the two groups before and after treatment were compared. Result:The total response rate in the experimental group was 84.00%（42/50），higher than 66.00%（33/50） in the control group （<italic>Z</italic>=-7.365，<italic>P</italic><0.05）. There was no significant difference in the scores of MBI，FMA， and NIHSS before treatment between the two groups. The MBI and FMA scores of the two groups increased （<italic>P</italic><0.01）， and the NIHSS scores decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the control group after treatment， the experimental group showed increased MBI and FMA scores and decreased NIHSS score （<italic>P</italic><0.05）. There was no significant difference in BDNF level between the two groups before and after treatment. The VEGF and SDF-1 levels in the peripheral blood of the two groups were higher than those before treatment （<italic>P</italic><0.05）， and the experimental group was higher than the control group （<italic>P</italic><0.05）. Conclusion:Qixian Tongluo prescription can effectively improve the clinical efficacy，the quality of life， and the prognosis of patients with cerebral infarction during convalescence. The underlying mechanism is associated with the promotion of the expression of endogenous VEGF and SDF-1 in the peripheral blood to activate the SDF-1/chemokine receptor 4（CXCR4） signaling pathway， induce the recruitment and mobilization of endothelial progenitor cells， and facilitate the angiogenesis and repair of ischemic brain tissues.

Strategies and Research Progress of Chinese Medicine in Prevention and Treatment of Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) seriously affects the quality of life in patients with type 2 diabetes mellitus. This paper reviews the role of Chinese medicine in the main treatment goal of DPN, including protecting pancreatic ß-cells, in the use of antioxidation therapy to delay disease progression, and in the endpoint of neural repair and regeneration. We propose that protecting the body from injury caused by high glucose and oxidative stress, and promoting repair and regeneration of nerves should be the research direction for the prevention and treatment of DPN.

Biotherapies in stroke.

Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a "glio-neurovascular niche". Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while "peripheral" stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell characterization, delivery route and in vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells and NSC are most investigated notably in clinical trials. Finally, we discuss perspectives concerning potential novel biotherapies such as combinatorial approaches (growth factor combined with cell therapy, in vitro optimization of cell products, or co-transplantation) and the development of biomaterials, which could be used as injectable hydrogel scaffold matrices that could protect a cell graft or selectively deliver drugs and growth factors into the post-stroke cavity at chronic stages. Considering the remaining questions about the best procedure and the safety cautions, we can hope that future translational research about biotherapies will bring more efficient treatments that will decrease post-stroke disability for many patients.