TMEM106B aggregation in neurodegenerative diseases: linking genetics to function.

BACKGROUND: Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious. MAIN BODY: Recent new studies reported that TMEM106B proteins form intracellular amyloid filaments which universally exist in various neurodegenerative diseases, sometimes being the dominant form of protein aggregation. In light of these new findings, in this review we systematically examined previous efforts in understanding the function of TMEM106B in physiological and pathological conditions. We propose that TMEM106B aggregations could recruit normal TMEM106B proteins and interfere with their function. CONCLUSIONS: TMEM106B mutations could lead to lysosome dysfunction by promoting the aggregation of TMEM106B and reducing these aggregations may restore lysosomal function, providing a potential therapeutic target for various neurodegenerative diseases.

Ginsenoside compound K acts via LRP1 to alleviate Amyloid ß42-induced neuroinflammation in microglia by suppressing NF-κB.

BACKGROUND: Alzheimer's disease (AD), has caused a mass of disability and mortality in elder populations, which increases global health burden. There are still limited effective disease-modifying drugs. Alleviating microglia-evoked neuroinflammation has become a promising treatment strategy for AD. Ginsenoside Compound K has been demonstrated to exhibit anti-inflammatory and neuroprotective benefits. Here we measured the effects of Ginsenoside Compound K in inhibiting amyloid-induced microglia inflammation and the possible molecular mechanisms and target of action in vitro. METHODS: The cytotoxicity of all chemical reagents on BV2 cells were evaluated using the MTT assay. qRT-PCR and ELISA were carried out to detect the inflammatory cytokines levels. Western blot was utilized to determine the effect of Ginsenoside Compound K on the nuclear factor-κB (NF-κB) p65 nuclear translocation. Antagonist Receptor Associated Protein (RAP) was used to verify the engagement of low-density lipoprotein receptor-related protein 1(LRP1). RESULTS: Ginsenoside Compound K diminished inflammatory cytokine production and reversed NF-κB p65 nuclear translocation induced by Aß42 oligomers. LRP1 expression was up-regulated by Ginsenoside Compound K. When LRP1 was blocked by antagonist RAP, the protective effect of Ginsenoside Compound K was massively eliminated. CONCLUSION: These observations provide evidence for anti-inflammatory effect of Ginsenoside Compound K through NF-κB pathway via LRP1 activation, and support further evaluation of Ginsenoside Compound K as a potential effective modulator for AD.

Cerebral blood flow in mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.

BACKGROUND: Reduced cerebral blood flow (CBF) contributes to the pathophysiology of Alzheimer's disease (AD). However, it is unclear whether there is a spatial-temporal-specific pattern of changed CBF in AD progression. METHODS: We systematically screened literature databases for cross-sectional and longitudinal studies reporting resting CBF or CBF velocity (CBFv) among patients with AD, mild cognitive impairment (MCI), and healthy controls (HCs). Standardised mean differences (SMDs) for CBF and mean differences (MDs) for CBFv were calculated. Quality assessments, meta-analysis, subgroup analysis, and meta-regression were subsequently performed (PROSPERO: CRD42020207548). RESULTS: Overall, 244 studies comprising 13,644 participants and 60 regions were included. Compared with HCs, AD subjects had decreased resting CBF throughout the brain (SMD range: -1.87 to -0.32), especially within the posterior cingulate and temporal-parietal regions. However, MCI subjects presented decreased CBF in ten regions with modest effects (SMD range: -0.86 to -0.25), especially in the precuneus. We identified the decreased CBF in the temporal, parietal, and hippocampal regions was associated with the lower AD Mini-Mental State Examination scores. CONCLUSIONS: Our findings suggest that the spatial-temporal pattern of CBF decreased from the precuneus, posterior cingulate and temporal-parietal regions to broader areas with progression from HC to MCI to AD, supporting the incorporation of CBF into the AD research framework.

[In vivo degradation and histocompatibility of modified chitosan based on conductive composite nerve conduit].

OBJECTIVE: To investigate the in vivo degradation and histocompatibility of modified chitosan based on conductive composite nerve conduit, so as to provide a new scaffold material for the construction of tissue engineered nerve. METHODS: The nano polypyrrole (PPy) was synthesized by microemulsion polymerization, blended with chitosan, and then formed conduit by injecting the mixed solution into a customized conduit formation model. After freeze-drying and deacidification, the nano PPy/chitosan composite conduit (CP conduit) was prepared. Then the CP conduits with different acetyl degree were resulted undergoing varying acetylation for 30, 60, and 90 minutes (CAP1, CAP2, CAP3 conduits). Fourier infrared absorption spectrum and scanning electron microscopy (SEM) were used to identify the conduits. And the conductivity was measured by four-probe conductometer. The above conduits were implanted after the subcutaneous fascial tunnels were made symmetrically on both sides of the back of 30 female Sprague Dawley rats. At 2, 4, 6, 8, 10, and 12 weeks after operation, the morphology, the microstructure, and the degradation rate were observed and measured to assess the in vivo degradation of conduits. HE staining and anti-macrophage immunofluorescence staining were performed to observe the histocompatibility in vivo. RESULTS: The characteristic peaks of the amide Ⅱ band around 1 562 cm -1 appeared after being acetylated, indicating that the acetylation modification of chitosan was successful. There was no significant difference in conductivity between conduits ( P>0.05). SEM observation showed that the surfaces of the conduits in all groups were similar with relatively smooth surface and compact structure. After the conduits were implanted into the rats, with the extension of time, all conduits were collapsed, especially on the CAP3 conduit. All conduits had different degrees of mass loss, and the higher the degree of acetylation, the greater the mass change ( P<0.05). SEM observation showed that there were more pores at 12 weeks after implantation, and the pores showed an increasing trend as the degree of acetylation increased. Histological observation showed that there were more macrophages and lymphocytes infiltration in each group at the early stage. With the extension of implantation time, lymphocytes decreased, fibroblasts increased, and collagen fibers proliferated significantly. CONCLUSION: The modified chitosan basedon conductive composite nerve conduit made of nano-PPy/chitosan composite with different acetylation degrees has good biocompatibility, conductivity, and biodegradability correlated with acetylation degree in vivo, which provide a new scaffold material for the construction of tissue engineered nerve.

Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.

BACKGROUND: Dysfunction of microglia has been increasingly recognized as a causative factor in Alzheimer's disease (AD); thus, developing medicines capable of restoring microglial functions is critically important and constitutes a promising therapeutic strategy. Honokiol is a natural neuroprotective compound extracted from Magnolia officinalis, which may play roles in AD therapy. OBJECTIVE: This study aimed to evaluate the role and the underlying mechanisms of honokiol in microglial phagocytosis. METHODS: MTT and flow cytometry were used to assess the cell viability and apoptosis, respectively. Phagocytic capacity, mitochondrial reactive oxygen species production, and membrane potential were evaluated using fluorescence microscopy. Seahorse XF24 extracellular flux analyzer was for cell glycolysis and oxidative phosphorylation detection. Mass spectrometry was applied for metabolites measurement. Quantitative real-time polymerase chain reaction and western blotting were performed to detect the mRNA and protein level of PPARγ and PGC1α, respectively. RESULTS: Honokiol alleviated Aß42-induced BV2 neurotoxicity. Honokiol promoted phagocytic efficiency of BV2 cells through reversing a metabolic switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production. Meanwhile, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential. Moreover, honokiol increased the expression of PPARγ and PGC1α, which might play positive roles in energy metabolism and microglial phagocytosis. CONCLUSION: In this study, honokiol was identified as an effect natural product capable of enhancing mitochondrial function thus promoting microglial phagocytic function.

Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study.

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

INTRODUCTION: The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population. METHODS: In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups. RESULTS: The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001). DISCUSSION: APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

[Preparation and biocompatibility of nano polypyrrole/chitin composite membrane].

Objective: To prepare nano polypyrrole (PPy)/chitin composite membrane and observe their biocompatibility. Methods: The nano PPy was synthesized by microemulsion polymerization, blended with chitosan and then formed membranes. The membranes were then modified by acetylation to get the experimental membranes (nano PPy/chitin composite membranes, group A). The chitosan membranes (group B) and chitin ones (group C) modified by acetylation acted as control. Scanning electron microscopy and FT-IR spectra were used to identify the nano PPy and the membranes of each group. And the conductivity of membranes of each group was measured. Schwann cells were co-cultured in vitro with each group membranes to observe the biocompatibility by inverted microscope observing, living cell staining, cell counting, and immunofluorescence staining. The lysozyme solution was used to evaluate the degradation of the membranes in vitro. Results: The FT-IR spectra showed that the characteristic vibrational absorption peaks of C=C from nano PPy appeared at 1 543.4 cm -1 and 1 458.4 cm -1. Scanning electron microscopy observation revealed that the size of nano PPy particles was about 100-200 nm. The nano PPy particles were synthesized. It was successful to turn chitosan to chitin by the acetylation, which was investigated by FT-IR analysis of membranes in groups A and C. The characteristic peaks of the amide Ⅱ band around 1 562 cm -1 appeared after acetylated modification. Conductivity test showed that the conductivity of membranes in group A was about (1.259 2±0.005 7)×10 -3 S/cm, while the conductivity of the membranes in groups B and C was not detected. The nano PPy particles uniformly distributed on the surface of membranes in group A were observed by scanning electron microscope; the membranes in control groups were smooth. As a result, the nano PPy/chitin composite membranes with electrical conductivity were obtained. The cultured Schwann cells were found to survive with good function by fluorescein diacetate live cell staining, soluble protein-100 immunofluorescence staining, and inverted microscope observing. The cell counting showed that the proliferation of Schwann cells after 2 days and 4 days of group A was more than that of the two control groups, and the differences were significant ( P<0.05). It indicated that the nano PPy/chitin composite membranes had better ability of adhesion and proliferation than those of chitosan and chitin membranes. The degradation of membranes in vitro showed that the degradation rates of membranes in groups A and C were significantly higher than those in group B at all time points ( P<0.05). In a word, the degradation performance of the membranes modified by acetylation was better than that of chitosan membranes under the same condition. Conclusion: The nano PPy and chitosan can be blended and modified by acetylation successfully. Nano PPy/chitin composite membranes had electrical conductivity, degradability, and good biocompatibility in vitro.

[Effect of short-term low-frequency electrical stimulation on nerve regeneration of delayed nerve defect during operation].

Objective: To explore the effect of short-term low-frequency electrical stimulation (SLES) during operation on nerve regeneration in delayed peripheral nerve injury with long gap. Methods: Thirty female adult Sprague Dawley rats, weighing 160-180 g, were used to prepare 13-mm defect model by trimming the nerve stumps. Then all rats were randomly divided into 2 groups, 15 rats in each group. After nerve defect was bridged by the contralateral normal sciatic nerve, SLES was applied in the experimental group, but was not in the control group. The spinal cords and dorsal root ganglions (DRGs) were harvested to carry out immunofluorescence histochemistry double staining for growth-associated proteins 43 (GAP-43) and brain-derived neurotrophic factor (BDNF) at 1, 2, and 7 days after repair. Fluorogold (FG) retrograde tracing was performed at 3 months after repair. The mid-portion regenerated segments were harvested to perform Meyer's trichrome staining, immunofluorescence double staining for neurofilament (NF) and soluble protein 100 (S-100) on the transversely or longitudinal sections at 3 months after repair. The segment of the distal sciatic nerve trunk was harvested for electron microscopy and morphometric analyses to measure the diameter of the myelinated axons, thickness of myelin sheaths, the G ratio, and the density of the myelinated nerve fibers. The gastrocnemius muscles of the operated sides were harvested to measure the relative wet weight ratios. Karnovsky-Root cholinesterase staining of the motor endplate was carried out. Results: In the experimental group, the expressions of GAP-43 and BDNF were higher than those in the control group at 1 and 2 days after repair. The number of labeled neurons in the anterior horn of gray matter in the spinal cord and DRGs at the operated side from the experimental group was more than that from the control group. Meyer's trichrome staining, immunofluorescence double staining, and the electron microscopy observation showed that the regenerated nerves were observed to develop better in the experimental group than the control group. The relative wet weight ratio of experimental group was significantly higher than that of the control group ( t=4.633, P=0.000). The size and the shape of the motor endplates in the experimental group were better than those in the control group. Conclusion: SLES can promote the regeneration ability of the short-term (1 month) delayed nerve injury with long gap to a certain extent.

Morphological Proof of nerve regeneration after long-term defects of rat sciatic nerves.

Unsatisfactory efficacy of clinical cure for long-term delayed injuries and other disadvantages such as the low regeneration rate and speed of axotomized neurons and the questionable reinnervation ability of atrophic target organ lead to inaction to the long-term delayed injuries. Here we attempted to use autologous nerve to bridge a long-term delayed 10-mm defect in SD rats based on some previous positive messages of basic and clinical research. In this study, for experimental groups, the rat sciatic nerve had been transected leaving a 10-mm defect, which was maintained for 3 or 6 months before implantation with the autologous graft. The non-grafted animals served as negative control. Measuring with electrophysiological and histological techniques, we find: (1) A number of long-term axotomized neurons survived and sustained certain degree of axonal regenerative capacity; (2) A few denervated Schwann cells survived and retained their ability to provide trophic support and myelinate axons in at least 6 months; (3) the chronically denervated muscle can partially be reinnervated by regenerated axons. But the quantity and the quality of the regenerated nerve fibers and the reinnervated muscle fibers were all poor. Thus these observations provide new positive morphological proof of nerve regeneration after long-term defects and further studies will be needed to increase the survival rate and the regenerative speed of long-term chronic axotomized neurons, enhance the support provided by denervated distal stumps and protect the target muscle.

Chitosan/polyglycolic acid nerve grafts for axon regeneration from prolonged axotomized neurons to chronically denervated segments.

Peripheral nerve regeneration for long-term delayed injuries is usually unsatisfied. Here we attempted to use a chitosan/polyglycolic acid (PGA) artificial nerve graft to bridge a long-term delayed 10-mm defect in SD rats based on the previous studies on the graft used for immediate repair of 30-mm-long dog sciatic nerve defects and for clinical treatment of a 35-mm-long median nerve defect at elbow of a human patient. In this study, for experimental groups, the rat sciatic nerve had been transected leaving a 10-mm defect, which was maintained for 3 or 6 months before implantation with the chitosan/PGA artificial nerve graft. The animals non-grafted or grafted with autograft served as negative or positive control group. In experiment groups, nerve regeneration with functional recovery was achieved as measured by electrophysiological and histological techniques, although differences in the quantity and the quality of the regenerated nerve were observed between the 3- and 6-month delayed subgroups. The results showed that: (1) a few denervated Schwann cells survived and sustained their ability to myelinate axons at least 6 months, and (2) the atrophic denervated muscle could be reinnervated by regenerated axons through new muscle-nerve connections. These observations provide the possibility of guiding regenerated axons from survived axotomized neurons to distal nerve stump by the chitosan/PGA artificial nerve graft.

[Time limit of repairing old sciatic nerve defect in rats].

OBJECTIVE: To investigate the time limit of repairing old sciatic nerve defect in rats and observe the repair effect of autogenous nerve transplantation on old sciatic nerve defect in rats. METHODS: Thirty-six SD rats of clean grade were randomized into 6 groups (n=6 per group). The animal model of nerve defect was made by transecting left sciatic nerve at the mid-thigh level. For groups A1, B1 and C1, defects were repaired by the contralateral autogenous nerve transplantation 1, 3 or 6 months after nerve damage and for the control groups of A2, B2 and C2, defects were not repaired. After operation, the gait, toe skin and leg muscle were examined weekly. Three months after autograft, a combination of electrophysiology examination, fluoro gold (FG) retrograde tracing and histological assessment including light microscopy, TEM was utilized to investigate the nerve functional recovery. RESULTS: Lameness and foot skin ulcers were observed in each group after nerve damage. At 2 months after autograft, such denervation symptoms were only improved in groups A1 and B1. At 3 months after autograft, the motor conduction velocity was (21.84 +/- 6.74), (20.02 +/- 4.17) and (16.09 +/- 8.21) m/s in groups A1, B1 and C1, respectively, showing no statistically significant difference between them (P > 0.05). The amplitude of compound muscle action potential (CAMP) was (12.68 +/- 4.38), (9.20 +/- 3.43) and (1.22 +/- 0.39) mV in groups A1, B1 and C1, respectively, indicating significant differences between groups A1, B1 and group C1 (P < 0.05). No CAMP was evident in groups A2, B2 and C2. FG retrograde tracing conducted 3 months after autograft showed that the positive cells were most common in group A1 with big soma, mild in group B1 and lest in group C1 with smallest soma. Gastrocnemius Masson staining showed that the fiber morphology of gastrocnemius in groups A1 and B1 was close to normal, while the rest 4 groups had an obvious atrophy of muscle fiber. The fiber cross-section area was (340.73 +/- 118.46), (299.88 +/- 119.75), (54.33 +/- 53.43), (78.60 +/- 51.38), (65.62 +/- 25.36), and (40.93 +/- 28.22) microm2 in groups A1, B1, C1, A2, B2 and C2, respectively, indicating a significant difference between groups A1, B1 and groups C1, A2, B2 (P < 0.05). Neurohistology observation showed that more regenerated nerve fibers were observed in group A1 and B1, but less in group C1. The myelin sheath was thick in groups A1 and B1, while it was thin in group C1. Only SCs and hyperplastic collagen fiber were found in groups A2, B2 and C2. CONCLUSION: Autogenous nerve transplantation is capable of repairing 1- and 3-month sciatic nerve defect to some degree in rat, but repair effect is not obvious on 6-month sciatic nerve defect in rats.