Tissue-engineered rhesus monkey nerve gratfs for the repair of long ulnar nerve defects：similar outcomes to autologous nerve gratfs

Acellular nerve allogratfs can help preserve normal nerve structure and extracellular matrix composition. These allogratfs have low immu-nogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autogratf. The gratf was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomo-rphology, electromyogram and immunohistochemistry ifndings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no signiifcant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neuroiflaments between the experimental and control groups. However, outcome was signiifcantly better in the experimental group than in the blank group. These ifndings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve gratf.     

Pre-degenerated peripheral nerves co-cultured with bone marrow-derived cells：a new technique for harvesting high-purity Schwann cells

Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regeneration requires an effective technique for obtaining purified Schwann cells. In vivo and in vitro pre-degeneration of peripheral nerves have been shown to obtain high-purity Schwann cells. We believed that in vitro pre-degeneration was simple and controllable, and available for the clinic. Thus, we co-cultured the crushed sciatic nerves with bone marrow-derived cells in vitro. Results demonstrated that, 3 hours after injury, a large number of mononuclear cells moved to the crushed nerves and a large number of bone marrow-derived cells infiltrated the nerve segments. These changes promoted the degradation of the nerve segments, and the dedifferentiation and proliferation of Schwann cells. Neural cell adhesion molecule and glial fibrillary acidic protein expression were detected in the crushed nerves. Schwann cell yield was 9.08 ± 2.01 × 104/mg. The purity of primary cultured Schwann cells was 88.4 ± 5.79%. These indicate a successful new method for obtaining Schwann cells of high purity and yield from adult crushed sciatic nerve using bone marrow-derived cells.     

Effects of cotransplantated Schwann cells and neural stem cells in a rat model of Alzheimer’s disease

Schwann cells (SCs) are significantly better at promoting neural stem cell (NSCs) proliferation, differentiation and synaptic formation when cocultured with NSCs in vitro, compared with cultured in a single nerve growth factor. The present study transplanted NSCs and SCs into the brain of a rat model of Alzheimer’s disease to investigate the effect of cotransplantation. Results show transplantation of both NSCs alone and NSCs + SCs significantly promoted learning and memory functions in Alzheimer’s disease rats, decreased glial fibrillary acidic protein and calcium binding protein S100β expression, but increased expression of the cholinergic neuron marker choline acetyl transferase mRNA. The effect of NSCs + SCs cotransplantation was, however, more significant. NSCs and SCs cotransplantation significantly reduced the number of astrocytes and increased cholinergic neurons, facilitating the recovery of learning and memory function, compared with NSCs transplantation alone.     

Can lithium enhance the extent of axon regeneration and neurological recovery following peripheral nerve trauma?

The clinical"gold standard"technique for attempting to restore function to nerves with a gap is to bridge the gap with sensory autografts.However,autografts induce good to excellent recovery only across short nerve gaps,in young patients,and when repairs are performed a short time post nerve trauma.Even under the best of conditions,<50%of patients recover good recovery.Although many alternative techniques have been tested,none is as effective as autografts.Therefore,alternative techniques are required that increase the percentage of patients who recover function and the extent of their recovery.This paper examines the actions of lithium,and how it appears to trigger all the cellular and molecular events required to promote axon regeneration,and how both in animal models and clinically,lithium administration enhances both the extent of axon regeneration and neurological recovery.The paper proposes more extensive clinical testing of lithium for its ability and reliability to increase the extent of axon regeneration and functional recovery.     

Propofol's effect on the sciatic nerve: Harmful or protective?

Propofol can inhibit the inflammatory response and reduce the secretion and harmful effects of astrocyte-derived proinflammatory cytokines.In this study,after propofol was injected into the injured sciatic nerve of mice,nuclear factor kappa B expression in the L4-6 segments of the spinal cord in the injured side was reduced,apoptosis was decreased,nerve myelin defects were alleviated,and the nerve conduction block was lessened.The experimental findings indicate that propofol inhibits the inflammatory and immune responses,decreases the expression of nuclear factor kappa B,and reduces apoptosis.These effects of propofol promote regeneration following sciatic nerve injury.     

Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve：viscoelasticity characterization

The optic nerve is a viscoelastic solid-like biomaterial.Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury.We hypothesized that stress relaxation and creep properties of the optic nerve change after injury.Moreover,human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal.To validate this hypothesis,a rabbit model of optic nerve injury was established using a clamp approach.At 7 days after injury,the vitreous body received a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells.At 30 days after injury,stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly,with pathological changes in the injured optic nerve also noticeably improved.These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves,and thereby contributes to nerve recovery.     

The reasons for end-to-side coaptation:how does lateral axon sprouting work?

Nerve fibers are attracted by sutureless end-to-side nerve coaptation into the recipient nerve. Opening a window in the epineurium enhances axon attraction and myelination. The authors analyze the features of nerve repair by end-to-side coaptation. They highlight the known mechanisms of axon sprouting and different hypotheses of start up signals (presence or absence of an epineurial window, role of Schwann cells, signaling from the distal trunk). The clinical literature is also presented and differences between experimental and clinical applications are pointed out. The authors propose their point of view and perspectives deriving from recent experimental and clinical experiences.     

Problematic eating behavior in childhood: do maternal feeding patterns play a role?

Past research indicates an association in adults and young people of emotional and contextual factors with a higher risk for the development of eating disorders or obesity. Few studies focus on problematic eating patterns in childhood, especially in association with parental feeding strategies. 482 mothers completed a questionnaire about eating behaviors and the weight status of their 1- to 10-year-old child as well as their own feeding strategies. A classification of the child's eating behavior (food responsiveness, emotional eating, external eating, eating time and meal structure) using hierarchical cluster analysis revealed a conspicuous eating pattern (10%) showing above-average values in all eating behaviors. Controlling for weight and demographic variables mothers of children with conspicuous eating patterns were characterized by restrictive strategies and were less likely to encourage or facilitate their child to control his or her eating. Similar problematic eating patterns were also identified in early childhood. The association of maternal feeding strategies--beyond weight control issues--with conspicuous eating patterns in children might indicate a possibility of early prevention through parent training.     

The methylation hypothesis: do epigenetic chromatin modifications play a role in epileptogenesis?

Any structural brain lesion can provoke epilepsy, although onset and progression of seizures as well as response to antiepileptic drug (AED) treatment remain difficult to predict in each patient. Tremendous work has focused on the development of new AED compounds with the intention to treat seizures. However, these efforts have not yet discovered a "magic bullet" that cures epilepsy in every patient or modifies disease progression. With the "methylation hypothesis" we propose that epigenetic mechanisms play a pivotal role in epileptogenesis in patients with structural lesions. "Epigenetics" is defined as information that is heritable during cell division other than the DNA sequence itself, that is, DNA methylation or histone tail modifications, which can produce lasting alterations in chromatin structure and gene expression. They are increasingly recognized as fundamental regulatory processes in central nervous system development, synaptic plasticity, and memory, and also play a role in neurologic disorders such as schizophrenia and spinal muscular atrophy. The methylation hypothesis suggests that seizures by themselves can induce epigenetic chromatin modifications, thereby aggravating the epileptogenic condition. The impact of the methylation hypothesis for new-onset epilepsy will be discussed. Unravelling of epigenetic pathomechanisms will also open new strategies to identify molecular targets for pharmacologic treatment in epilepsies.     

Role of inflammatory cytokines in peripheral nerve injury

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro-and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.     

Polymorphisms of platelet adhesive receptors: do they play a role in primary intracerebral hemorrhage?

BACKGROUND: Several reports suggested that polymorphisms affecting the structure or level of the main adhesive platelet glycoproteins (GPs) could behave as genetic risk factors for arterial thrombotic disorders. However, very few reports analyzed the significance of these polymorphisms in bleeding disorders. Interestingly, one study suggested a role of the 807 C/T polymorphism of the collagen receptor GP Ia in the severity of the bleeding manifestations in von Willebrand disease. The aim of this study was to evaluate the role of frequent polymorphisms affecting platelet GPs in primary intracerebral hemorrhage (PIH), the third most frequent cause of cerebrovascular disorder. METHODS: We evaluated the role of four putative prothrombotic polymorphisms: GP Ia [807 C/T, and human platelet alloantigen system 5 (HPA-5)], GP Ibalpha (variable number of tandem repeats), and GP IIIa (HPA-1) in 141 Caucasian patients diagnosed of PIH, 141 race-, age-, sex- and risk factor-matched controls, and 446 subjects from the general population. RESULTS: The frequency of genotypes and alleles were similar between patients and controls. CONCLUSIONS: Our results suggest that these polymorphisms play a minor role in PIH.     

Is Goshinjo therapy effective in cognitive impairment after severe traumatic brain injury?

We report a case of a 21-year-old man who had severe traumatic brain injury as a result of an accident at the age of 16 years. Two years and 4 months after the trauma, at the age of 19 years, he still had severe right hemiplegia and cognitive dysfunction including aphasia and attention and memory disturbance. Conventional rehabilitation programs could not resolve all of the neuropsychological problems. He started receiving Goshinjo therapy over a period of 22 months. Following the therapy, significant improvements in verbal intelligence quotient (assessed by the Wechsler Adult Intelligence Scale-Third Edition) and attention and concentration function (using the Wechsler Memory Scale-Revised), and remission of traumatic epilepsy were observed. Goshinjo therapy is suspected to be effective in the treatment of cognitive dysfunction in the chronic stage after severe traumatic brain injury.     

Traumatic brain injury and palliative care: a retrospective analysis of 49 patients receiving palliative care during 2013–2016 in Turkey

Traumatic brain injury(TBI),which is seen more in young adults,affects both patients and their families.The need for palliative care in TBI and the limits of the care requirement are not clear.The aim of this study was to investigate the length of stay in the palliative care center(PCC),Turkey,the status of patients at discharge,and the need for palliative care in patients with TBI.The medical records of 49 patients with TBI receiving palliative care in PCC during 2013–2016 were retrospectively collected,including age and gender of patients,the length of stay in PCC,the cause of TBI,diagnosis,Glasgow Coma Scale score,Glas gow Outcome Scale score,Karnofsky Performance Status score,mobilization status,nutrition route(oral,percutaneous endoscopic gastrostomy),pressure ulcers,and discharge status.These patients were aged 45.4 ± 20.2 years.The median length of stay in the PCC was 34.0 days.These included TBI patients had a Glasg ow Coma Scale score ≤ 8,were not mobilized,received tracheostomy and percutaneous endoscopic gastrostomy nutrition,and had pressure ulcers.No difference was found between those who were discharged to their home or other places(rehabilitation centre,intensive care unit and death) in respect of mobilization,percutaneous endoscopic gastrostomy,tracheostomy and pressure ulcers.TBI patients who were followed up in PCC were determined to be relatively young patients(45.4 ± 20.2 years) with mobilization and nutrition problems and pressure ulcer formation.As TBI patients have complex health conditions that require palliative care from the time of admittance to intensive care unit,provision of palliative care services should be integrated with clinical applications.     

Axonal degeneration of the ulnar nerve secondary to carpal tunnel syndrome: fact or fiction?

The distribution of sensory symptoms in carpal tunnel syndrome is strongly dependent on the degree of electrophysiological dysfunction of the median nerve. The association between carpal tunnel syndrome and ulnar nerve entrapment is still unclear. In this study, we measured ulnar nerve function in 82 patients with carpal tunnel syndrome. The patients were divided into group I with minimal carpal tunnel syndrome (n = 35) and group II with mild to moderate carpal tunnel syndrome (n = 47) according to electrophysiological data. Sixty-one age- and sex-matched subjects without carpal tunnel syndrome were used as a control group. There were no significant differences in ulnar sensory nerve peak latencies or conduction velocities from the 4th and 5th fingers between patients with carpal tunnel syndrome and the control group. The ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were lower in patients with carpal tunnel syndrome than in the control group. The ratios of the ulnar sensory nerve action potential amplitudes from the 4th and 5th fingers were almost the same in patients with carpal tunnel syndrome as in the control group. These findings indicate that in patients with minimal to moderate carpal tunnel syndrome, there is some electrophysiological evidence of traction on the adjacent ulnar nerve fibers. The findings do not indicate axonal degeneration of the ulnar nerve.     

Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson’s disease

Autophagy has been shown to play an important role in Parkinson’s disease.We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson’s disease through affecting autophagy.In this study,6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells(SKP-SCs).The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine,reduced excessive autophagy,increased tyrosine hydroxylase expression,reducedα-synuclein expression,reduced the autophagosome number,and activated the PI3K/AKT/mTOR pathway.Autophagy activator rapamycin inhibited the effects of SKP-SCs,and autophagy inhibitor 3-methyladenine had the opposite effect.These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy,thereby exhibiting a neuroprotective effect in a cellular model of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University(approval No.S20181009-205)on October 9,2018.     

Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca 2+ influx, inhibit calcium overload, and diminish Ca 2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.     

“Three Methods and Three Points” regulates p38 mitogen-activated protein kinase in the dorsal horn of the spinal cord in a rat model of sciatic nerve injury

Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian, Bo, and Rou method in Yinmen(BL37), Yanglingquan(GB34), and Weizhong(BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood. This study established rat models of sciatic nerve injury using the crushing method. Rats received Chinese tuina in accordance with the principle of Three Methods and Three Points, once daily for 20 days. Tuina intervention reduced paw withdrawal latency and improved wet weight of the gastrocnemius muscle, as well as promoting morphological recovery of sciatic nerve fibers, Schwann cells, and axons. The protein expression levels of phospho-p38 mitogen-activated protein kinase, tumor necrosis factor-α, and interleukin-1β also decreased. These findings indicate that Three Methods and Three Points promoted morphological recovery and improved behavior of rats with peripheral nerve injury.     

Adipose-brain crosstalk: do adipokines have a role in neuroprotection?

<正>Accumulating evidence from epidemiological and experimental studies indicate that obesity,and its related metabolic consequences of insulin resistance and type 2 diabetes,are associated with accelerated cognitive decline(Yates et al.,2012).The etiology of neurodegeneration in obesity is undoubtedly complex,with vascular,metabolic,inflammatory,and structural changes all likely to play a role(Yates et al.,     

Sexual dysfunction in obese women: Does obstructive sleep apnea play a role?

BackgroundFemale sexual dysfunction (FSD) is diagnosed when an impairment in the sexual response cycle is associated with distress in women. The association between obstructive sleep apnea (OSA) and FSD has been poorly investigated with conflicting results.AimTo assess the role of OSA in determining FSD in pre menopausal obese women.MethodsForty-six women underwent standard polysomnography. Data on sexual function and sexual-related distress were obtained using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS). Women with both abnormal FSFI and FSDS scores were classified as having FSD.ResultsThirty-one women were classified as having OSA. Fourteen (30.4%) women had both sexual difficulties and sexual distress resulting in FSD; they showed higher values of sleep time spent with SpO₂ <90% (T₉₀ 16.8 ± 24.4 vs. 3.2 ± 5.2%; p=0.004). FSD was present in 10 women with OSA (32.2%); in this group T₉₀ was higher (23.5 ± 26.3) in women with FSD than in those without FSD (4.8 ± 5.8; p = 0.003). In a logistic multiple regression analysis, T₉₀ was the only factor associated with an increased risk for FSD (odds ratio [OR] 1.07) (confidence interval [CI]) 1.006–1.13]; p=0.03).ConclusionsIn premenopausal obese women the presence of FSD is correlated with OSA only when nocturnal hypoxia is present.