Serotonin controls axon and neuronal regeneration in the nervous system:lessons from regenerating animal models

Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.

Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography(CT) scan, histopathology and enzyme-linked immune sorbent assay(ELISA)were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth,gingival recession, attachment loss and alveolar bone regeneration values were(3.72 ± 1.18) mm vs.(6.56 ± 1.47) mm,(1.67 ± 0.59)mm vs.(2.38 ± 0.61) mm,(5.56 ± 1.29) mm vs.(8.61 ± 1.72) mm, and(25.65 ± 5.13) mm3 vs.(9.48 ± 1.78) mm3 in the icariin group and0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta(IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.

Nonhuman primate models of focal cerebral ischemia

Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber.A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration.In this study,we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve.Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components（complement factor I,C1q-A,C1q-B,C2,C3,C4,C5,C7,C8β and complement factor D） in the nerve regeneration conditioned fluid and each varied at different time points.These findings suggest that all these complement components have a functional role in nerve regeneration.

The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery.

Co-culture of oligodendrocytes and neurons can be used to assess drugs for axon regeneration in the central nervous system

We present a novel in vitro model in which to investigate the efficacy of experimental drugs for the promotion of axon regeneration in the central nervous system. We co-cultured rat hippocampal neurons and cerebral cortical oligodendrocytes, and tested the co-culture system using a Nogo-66 receptor antagonist peptide（NEP1–40）, which promotes axonal growth. Primary cultured oligodendrocytes suppressed axonal growth in the rat hippocampus, but NEP1–40 stimulated axonal growth in the co-culture system. Our results confirm the validity of the neuron-oligodendrocyte co-culture system as an assay for the evaluation of drugs for axon regeneration in the central nervous system.

Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

A mouse model of weight-drop closed head injury:emphasis on cognitive and neurological deficiency

Traumatic brain injury（TBI） is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of potential therapeutics,which are effective in the treatment of TBI,animal models of TBI should be established and standardized.In this study,we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model.We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice.Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury.Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.

Sono-assisted preparation of magnetic ferroferric oxide/graphene oxide nanoparticles and application on dye removal

A simple ultrasound-assisted co-precipitation method was developed to prepare ferroferric oxide/graphene oxide magnetic nanoparticles(Fe_3O_4/CO MNPs).The hysteresis loop of Fe_3O_4/GO MNPs demonstrated that the sample was typical of superparamagnetic material.The samples were characterized by transmission electron microscope,and it is found that the particles are of small size.The Fe_3O_4/GO MNPs were further used as an adsorbent to remove Rhodamine B.The effects of initial pH of the solution,the dosage of adsorbent,temperature,contact time and the presence of interfering dyes on adsorption performance were investigated as well.The adsorption equilibrium and kinetics data were fitted well with the Freundlich isotherm and the pseudosecond-order kinetic model respectively.The adsorption process followed intra-particle diffusion model with more than one process affecting the adsorption of Rhodamine B.And the adsorption process was endothermic in nature.Furthermore,the magnetic composite with a high adsorption capacity of Rhodamine B could be effectively and simply separated using an external magnetic field.And the used particles could be regenerated and recycled easily.The magnetic composite could find potential applications for the removal of dye pollutants.

Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

Vascularization of acellular nerves has been shown to contribute to nerve bridging.In this study,we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves.The rat nerve defects were treated with acellular nerve grafting（control group） alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein（experimental group）.As shown through two-dimensional imaging,the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation,and gradually covered the entire graft at day 21.The vascular density,vascular area,and the velocity of revascularization in the experimental group were all higher than those in the control group.These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.