Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats.

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation. On the basis of previously studied nerve conduits, we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner. In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors, increased the expression of Jun and Sox2 genes, decreased the expression of Mbp and Krox20 genes in Schwann cells, and reprogrammed Schwann cells to a repair phenotype. Furthermore, mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia. The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects. Sustained release of exosomes greatly accelerated nerve healing and improved nerve function. These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

Chitin scaffold combined with autologous small nerve repairs sciatic nerve defects.

Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects, it has many clinical limitations. As an alternative, various tissue-engineered nerve grafts have been developed to substitute for autologous nerves. In this study, a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats. The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath, reduced atrophy of the target muscle, and effectively restored neurological function. When the epineurium of the small autogenous nerve was removed, the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation. These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds. The study was approved by the Research Ethics Committee of Peking University People's Hospital (approval No. 2019PHE27) on October 18, 2019.

Combining chitin biological conduits with small autogenous nerves and platelet-rich plasma for the repair of sciatic nerve defects in rats.

AIMS: Peripheral nerve defects are often difficult to recover from, and there is no optimal repair method. Therefore, it is important to explore new methods of repairing peripheral nerve defects. This study explored the efficacy of nerve grafts constructed from chitin biological conduits combined with small autogenous nerves (SANs) and platelet-rich plasma (PRP) for repairing 10-mm sciatic nerve defects in rats. METHODS: To prepare 10-mm sciatic nerve defects, SANs were first harvested and PRP was extracted. The nerve grafts consisted of chitin biological conduits combined with SAN and PRP, and were used to repair rat sciatic nerve defects. These examinations, including measurements of axon growth efficiency, a gait analysis, electrophysiological tests, counts of regenerated myelinated fibers and observations of their morphology, histological evaluation of the gastrocnemius muscle, retrograde tracing with Fluor-Gold (FG), and motor endplates (MEPs) distribution analysis, were conducted to evaluate the repair status. RESULTS: Two weeks after nerve transplantation, the rate and number of regenerated axons in the PRP-SAN group improved compared with those in the PRP, SAN, and Hollow groups. The PRP-SAN group exhibited better recovery in terms of the sciatic functional index value, composite action potential intensity, myelinated nerve fiber density, myelin sheath thickness, and gastrectomy tissue at 12 weeks after transplantation, compared with the PRP and SAN groups. The results of FG retrograde tracing and MEPs analyses showed that numbers of FG-positive sensory neurons and motor neurons as well as MEPs distribution density were higher in the PRP-SAN group than in the PRP or SAN group. CONCLUSIONS: Nerve grafts comprising chitin biological conduits combined with SANs and PRP significantly improved the repair of 10-mm sciatic nerve defects in rats and may have therapeutic potential for repairing peripheral nerve defects in future applications.

A novel tissue engineered nerve graft constructed with autologous vein and nerve microtissue repairs a long-segment sciatic nerve defect.

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

Value of Adjuvant Radiotherapy for Thymoma with Myasthenia Gravis after Extended Thymectomy.

BACKGROUND: The co-existence of myasthenia gravis (MG) and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this study was to investigate adjuvant radiotherapy for thymoma with MG after extended thymectomy. METHODS: A total of 181 patients with both MG and thymoma were recruited between 2003 and 2014 at Tongren Hospital, China. Among all the patients, 157 patients received radiation therapy after surgery (Group A); whereas the other 24 patients did not receive radiation therapy (Group B). According to the time that patients started mediastinal radiation therapy, we subdivided the 157 patients in Group A into subgroups (1-month subgroup, n = 98; 2-month subgroup, n = 7; and 3-month subgroup, n = 52). We then compared the effect of the mediastinal radiation therapy across these different groups using the survival rate, the rate of postoperative myasthenic crisis, and the complete stable remission (CSR) rate as the primary endpoints. RESULTS: There was a significant difference in the occurrence of postoperative myasthenic crisis between 1-month subgroup and Group B (χ2 = 4.631, P = 0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group B, respectively. The overall survival rates of 1-month subgroup, 3-month subgroup, and Group B were 88.8%, 83.3%, and 77.3%, respectively. Analysis on the Kaplan-Meier survival curves demonstrated that within 8 years after surgery, there was no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup and Group B, and between 3-month subgroup and Group B; over 8 years after surgery, the disease-free survival rates in 1-month subgroup, 3-month subgroup and Group B were 79.4%, 70.6%, and 55.3%, respectively. CONCLUSIONS: Adjuvant radiation within 1 month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing the possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR.

Roles of neural stem cells in the repair of peripheral nerve injury.

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

[Clinical study of optic neuritis combined with viral hepatitis].

OBJECTIVE: To investigate the clinical manifestation, management and prognosis of optic neuritis combined with viral hepatitis. METHODS: Retrospective study case series. Clinical data from twenty patients with optic neuritis combined with hepatitis who were hospitalized in Beijing Tongren Hospital neural eye ward from September 2003 to June 2010 were collected, the clinical characteristics and visual field changes in the group of patients were summarized, and comparison between the vision before and after treatment was made by the Wingerchuk vision classification. RESULTS: Among the twenty patients, eighteen patients had chronic hepatitis B and two patients had chronic hepatitis C. Thirteen (65%) patient were monocular, sixteen (80%) patients were single-phase course. Twenty-seven eyes were affected. Disc edema was very common which was found in 14 eyes (52%), severe vision impairment (Best corrected visual acuity worse than 20/200) were recorded in 19 eyes (70%). Lower altitudinal visual field impairment was more common which was found in 10 eyes (50%). All patients were followed for 3 months after steroid therapy, complete visual recovery or significant improvement was seen in only 3 eyes (11%) or 4 eyes (15%). Minor improvement was seen in 12 eyes (44%), while 8 eyes (30%) had no improvement. CONCLUSIONS: In this study, optic neuritis combined with hepatitis usually showed severe visual impairment. Although the vision of some patients could completely recover after steroid therapy, most of the patients had poor recovery. Combination of steroid and anti-viral therapy should be considered in the management of optic neuritis combined with hepatitis.

Somatosensory disinhibition in patients with paroxysmal kinesigenic dyskinesia.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent brief episodes of chorea and dystonia induced by sudden movement. Whether the central nervous system is hyper- or hypoexcitable in PKD remains undetermined. The aim of our study was to compare the somatosensory evoked potential (SEP) recovery cycle, a marker of somatosensory system excitability, in PKD patients and controls. METHODS: Twenty-four PKD patients (mean age of (20.0±5.3) years; 21 males, 3 females) and 18 control age-matched subjects (mean age of (22.0±5.0) years; 17 males, 1 female) were studied. The stimuli were delivered to the median nerve in the affected dominant arm in patients and in the dominant arm in controls. The change in SEP amplitude was measured after paired electrical stimulation at interstimulus intervals (ISIs) of 5, 20, and 40 ms. The SEPs evoked by S2 (test stimulus) were calculated by subtracting the response to S1 (the conditioning stimulus) from the response to a pair of stimuli (S1+S2), and their amplitudes were compared with those of the control response (S1) at each ISI. Analysis of variance (ANOVA) or equivalent was used for non-parametric data. RESULTS: In patients, the P27 amplitude after the single stimulus (S1) was significantly larger than that after the control stimulus. The (S2/S1)×100 ratio for P14 and N30 SEPs did not differ significantly between PKD patients and normal subjects at ISI of 5 ms but were significantly higher in patients at ISIs of 20 and 40 ms (P<0.05). CONCLUSIONS: Somatosensory system disinhibition takes place in PKD. The finding of reduced suppression of different SEPs, each thought to have a different origin, suggests an abnormality of intracortical and subcortical inhibitory circuits.

[Clinical characteristics of non-arteritic anterior ischemic optic neuropathy].

OBJECTIVE: To evaluate the demographic, risk factors and clinical characteristics of non-arteritic anterior ischemic optic neuropathy (NAION) and provide clinical guidance for this blindness disease. METHODS: Retrospective study was used to investigate the data, which consists of 96 NAION consecutive patients in neurology department of our hospital from 2005 to 2008. RESULTS: The average age of NAION patients is 50.90 +/- 8.88 years (range, 34 - 78 years) and the median is 50 y. About 68.8% of patients are male. The prevalence of hypertension, diabetes mellitus and abnormal lipid level is 34.4% (33/96), 29.2% (21/96) and 59.4% (57/93) respectively. The predominant patterns of visual field loss are altitudinal and accurate defects. Visual acuity was improved (change of >/= 3 lines) in 44.4% of patients. CONCLUSIONS: The age of onset in NAION is relatively early in life, compared with cerebral vascular disease, and male seems to have a high incidence. The most common risk factor is metabolic syndrome. Subcortical and periventricular white matter lesions and myocardial ischemia might associate with NAION. Visual acuity showed improvement in some patients, but the long outcome is poor.

[Clinical characteristic of optic neuritis and its relevancy with human leukocyte antigen].

OBJECTIVE: To investigate clinical characteristics of optic neuritis and its association with HLA (human leukocyte antigen). METHOD: The clinical data of 42 patients with optic neuritis were collected and flow polymerase chain reaction-reverse sequence specific oligonucleotide probe (PCR-rSSOP) was used to determine the genotype of HLA-DRB1. RESULTS: Two patients confirmed as Leber hereditary optic neuropathy by gene sequencing were excluded from the study. The complaint of pain was found in the patients (31/40) of optic neuritis. The visual field defect varied with patients and central and pericentral scotoma were demonstrated in 7 patients of 17. Of 40 patients with optic neuritis, 20 (50.0%) showed multifocal brain lesions in white matter by MR scanning. 26 of 38 patients had increased STIR signals. Inflammatory demyelinating changes were found in cerebral spinal fluid in 21 patients (80.8%). Out of demonstrated brain abnormal was revealed in 29 (72.5%) patients using MRI and/or CSF examination. The rate of HLA-DRB1(*)15 in the patients (35.0%) was much higher than control (19.4%), (chi(2) = 4.2328, P = 0.0397). Frequencies of HLA-DRB1(*)15 increased significantly in 26 female patients. The increased frequencies of HLA-DRB1(*)15 were associated with CSF abnormality and no relevancy was found with onset times, brain MR changes and increase of optic nerve signals. Acute optic neuritis responded well to intravenous megadose of methylprednisolone or immunoglobulin. CONCLUSIONS: Most of optic neuritis was characterized as clinical inflammatory demyelinating disease. HLA-DRB1(*)15 might correlated with genetic susceptibility of female patients with optic neuritis.