Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra

Tyrosine hydroxylase is a key enzyme in dopamine biosynthesis. Change in tyrosine hydroxylase expression in the nigrostriatal system is closely related to the occurrence and development of Parkinson＇s disease. Verbascoside, an extract from Radix Rehmanniae Praeparata has been shown to be clinically effective in treating Parkinson＇s disease. However, the underlying mechanisms remain unclear. It is hypothesized that the effects of verbascoside on Parkinson＇s disease are related to tyrosine hydroxylase expression change in the nigrostriatal system. Rat models of Parkinson＇s disease were established and verbascoside（60 mg/kg） was administered intraperitoneally once a day. After 6 weeks of verbascoside treatment, rat rotational behavior was alleviated; tyrosine hydroxylase m RNA and protein expression and the number of tyrosine hydroxylase-immunoreactive neurons in the rat right substantia nigra were significantly higher than the Parkinson＇s model group. These findings suggest that the mechanism by which verbascoside treats Parkinson＇s disease is related to the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra.

Nanotechnology and bio-functionalisation for peripheral nerve regeneration

There is a high clinical demand for new smart biomaterials, which stimulate neuronal cell proliferation, migration and increase cell-material interaction to facilitate nerve regeneration across these critical-sized defects. This article briefly reviews several up-to-date published studies using Arginine-Glycine-Aspartic acid peptide sequence, nanocomposite based on polyhedral oligomeric silsesquioxane nanoparticle and nanofibrous scaffolds as promising strategies to enhance peripheral nerve regeneration by influencing cellular behaviour such as attachment, spreading and proliferation. The aim is to establish the potent manipulations, which are simple and easy to employ in the clinical conditions for nerve regeneration and repair.

Stem cells:a promising candidate to treat neurological disorders

Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system.Therefore,based on the regenerative capacity of stem cells,transplantation therapies of various stem cells have been tested in basic research and preclinical trials,and some have shown great prospects.This manuscript overviews the cellular and molecular characteristics of embryonic stem cells,induced pluripotent stem cells,neural stem cells,retinal stem/progenitor cells,mesenchymal stem/stromal cells,and their derivatives in vivo and in vitro as sources for regenerative therapy.These cells have all been considered as candidates to treat several major neurological disorders and diseases,owing to their self-renewal capacity,multi-directional differentiation,neurotrophic properties,and immune modulation effects.We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases,including Parkinson＇s disease,Alzheimer＇s disease,and age-related macular degeneration,as well as traumatic brain injury and glioblastoma.In spite of a few unsuccessful cases,risks of tumorigenicity,and ethical concerns,most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease.In summary,these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders.Thus,stem cells are a promising candidate for the treatment of nervous system diseases.

Electroacupuncture pretreatment exhibits antidepressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui（GV20） and Yintang（GV29） acupoints was performed daily（1 m A, 2 Hz, discontinuous wave, 20 minutes） prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins（COG） database. Twenty-seven differential proteins（uncharacteristic proteins expected） were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.

Panax notoginseng saponins improve recovery after spinal cord transection by upregulating neurotrophic factors

Saponins extracted from Panax notoginseng are neuroprotective, but the mechanisms underlying this effect remain unclear. In the present study, we established a rat model of thoracic（T10） spinal cord transection, and injected Panax notoginseng saponins（100 mg/kg） or saline 30 minutes after injury. Locomotor functions were assessed using the Basso, Beattie, and Bresnahan（BBB） scale from 1 to 30 days after injury, and immunohistochemistry was carried out in the ventral horn of the spinal cord at 1 and 7 days to determine expression of nerve growth factor（NGF） and brain-derived neurotrophic factor（BDNF）. Our results show that at 7–30 days post injury, the BBB score was higher in rats treated with Panax notoginseng saponins than in those that received saline. Furthermore, at 7 days, more NGF- and BDNF-immunoreactive neurons were observed in the ventral horn of the spinal cord of rats that had received Panax notoginseng saponins than in those that received saline. These results indicate that Panax notoginseng saponins caused an upregulation of NGF and BDNF in rats with spinal cord transection, and improved hindlimb motor function.

Buyang Huanwu decoction up-regulates Notch1 gene expression in injured spinal cord

Expression of genes in the Notch signaling pathway is altered in the injured spinal cord, which indicates that Notch participates in repair after spinal cord injury. Buyang Huanwu decoction, a traditional Chinese herbal preparation, can promote the growth of nerve cells and nerve fibers; however, it is unclear whether Buyang Huanwu decoction affects the Notch signaling pathway in injured spinal cord. In this study, a rat model was established by injuring the T10 spinal cord. At 2 days after injury, rats were intragastrically administered 2 m L of 0.8 g/m L Buyang Huanwu decoction daily until sacrifice. Real-time reverse transcription polymerase chain reaction analysis demonstrated that at 7, 14 and 28 days after injury, the expression of Notch1 was increased in the Buyang Huanwu decoction group compared with controls. These findings confirm that Buyang Huanwu decoction can promote the expression of Notch1 in rats with incomplete spinal cord injury, and may indicate a mechanism to promote the repair of spinal cord injury.

Shuanghuanglian injection downregulates nuclear factor-kappa B expression in mice with viral encephalitis

A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.

Moxibustion upregulates hippocampal progranulin expression

In China,moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome,but its mechanisms are largely unknown.More recently,the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome,and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis.In the present study,we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms.Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome.The acupoints Guanyuan（CV4） and Zusanli（ST36,bilateral） were simultaneously administered moxibustion.Untreated chronic fatigue syndrome rats and normal rats were used as controls.Results from the forced swimming test,open field test,tail suspension test,real-time PCR,enzyme-linked immunosorbent assay,and western blot assay showed that moxibustion treatment decreased m RNA expression of corticotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone and corticosterone levels in plasma,and markedly increased progranulin m RNA and protein expression in the hippocampus.These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome,at least in part,by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.