Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and ...Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is k...Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.展开更多
Neurofilaments (NFs) were isolated from bovine spinal cord. The structure of purified NFs was studied by scanning tunneling microscopy (STM). The STM images showed that NF was composed of a long core filament and nume...Neurofilaments (NFs) were isolated from bovine spinal cord. The structure of purified NFs was studied by scanning tunneling microscopy (STM). The STM images showed that NF was composed of a long core filament and numerous sidearms flanking the rod regularly. The diameter of the rod was about 10 nm (10.2±0.8 nm). Most of the sidearms were short and the distance between two adjacent sidearms was approximately 10 nm. There were some long sidearms between two proximal core filaments. The distance between two adjacent long sidearms was 21 nm. A three-quarter-staggered fashion of native NF structure was put forward.展开更多
Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the mem...Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HILFN.Methods Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^(-/-)) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.Results The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilamentpositive nerve fibers in the cornu ammonis 1(CA1) and dentate gyrus(DG) hippocampal areas in wildtype mice. However, TRPV4^(-/-)mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.Conclusion TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus,which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.展开更多
Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of ...Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of the spinal cord in some cases.A limited number of axons(20-50)can cross the bridge and re-connect the caudal stump of the spinal cord with small neurons located in the rostral stump of the spinal cord.This axonal regeneration appears to be related to the recovery of hind-limb movements after initial paralysis.The present study extends previous studies and shows that after transection of the lumbar spinal cord in lizards,a glial-connective tissue bridge that reconnects the rostral and caudal stumps of the interrupted spinal cord is formed at 11-34 days post-injury.Following an initial paralysis some recovery of hindlimb movements occurs within 1-3 months post-injury.Immunohistochemical and ultrastructural analysis for a growth associated protein 43(GAP-43)of 48-50 k Da shows that sparse GAP-43 positive axons are present in the proximal stump of the spinal cord but their number decreased in the bridge at 11-34 days post-transection.Few immunolabeled axons with a neurofilament protein of 200-220 k Da were seen in the bridge at 11-22 days post-transection but their number increased at 34 days and 3 months post-amputation in lizards that have recovered some hindlimb movements.Numerous neurons in the rostral and caudal stumps of the spinal cord were also labeled for GAP43,a cytoplasmic protein that is trans-located into their axonal growth cones.This indicates that GAP-43 biosynthesis is related to axonal regeneration and sprouting from neurons that were damaged by the transection.Taken together,previous studies that utilized tract-tracing technique to label the present observations confirm that a limited axonal re-connection of the transected spinal cord occurs 1-3 months post-injury in lizards.The few regenerating-sprouting axons within the bridge reconnect the caudal with the rostral stumps of the spinal cord,and likely contribute to activate the neural circuits that sustain the limited but important recovery of hind-limb movements after initial paralysis.The surgical procedures utilized in the study followed the regulations on animal care and experimental procedures under the Italian Guidelines(art.5,DL 116/92).展开更多
Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer...Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.展开更多
Objective:To investigate the morphological changes of the neuronal neurites in diabetic rabbit brain. Methods: Twenty- four New Zealand White rabbits were divided into 2 groups: control group and type Ⅱ diabetic grou...Objective:To investigate the morphological changes of the neuronal neurites in diabetic rabbit brain. Methods: Twenty- four New Zealand White rabbits were divided into 2 groups: control group and type Ⅱ diabetic group induced by high - carbohydrate and high- fat diet. The levels of blood sugar and insulin were detected at week 0(w0), w4, w8, w13, w18, w23 and w28. Brain tissue was stained by Nissl staining and immunolistochemistry with a specific antibody to neurofilament proteins. Result: In diabetic rabbits, the amount of large pyramidal neuron was significantly reduced, and neuronal neurites became swollen, whorled, disrupted and changed in caliber. In hippocampus CA1 region neurofilament staining was very weak. Conclusion: Neurotoxicity of chronic hyperglycemia might be relevant to vascular chronic complications, which affected the expression of NF and led to neurophysiological and structural changes in the brain of rabbits with type Ⅱ diabetes.展开更多
Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and th...Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.展开更多
Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect of neural stem cell...Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear.To examine this,we established a rat model of traumatic brain injury by controlled cortical impact.At 72 hours after injury,2 × 10~7 cells/m L neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells（3 m L） were injected into the injured cortex.At 1–3 weeks after transplantation,expression of neurofilament 200,microtubule-associated protein 2,actin,calmodulin,and beta-catenin were remarkably increased in the injury sites.These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival,growth,and differentiation in the injury sites.The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.展开更多
Flavonoids from Huangqin（dried roots of Scutellaria baicalensis Georgi） have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9-10 spinal cord...Flavonoids from Huangqin（dried roots of Scutellaria baicalensis Georgi） have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9-10 spinal cord segments of rats were damaged using Allen＇s method to establish a rat spinal cord injury model. Before model establishment, Huangqin flavonoid extraction（12.5 g/kg） was administered intragastrically for 1 week until 28 days after model establishment. Methylprednisolone（30 mg/kg） was injected into the tail vein at 30 minutes after model establishment as a positive control. Basso, Beattie, and Bresnahan locomotor scale scores were used to assess hind limb motor function. Hematoxylin-eosin staining was used to detect pathological changes in the injured spinal cord. Immunofluorescence and western blot assays were performed to measure immunoreactivity and expression levels of brain-derived neurotrophic factor, neuronal marker neurofilament protein, microglial marker CD11 b and astrocyte marker glial fibrillary acidic protein in the injured spinal cord. Huangqin flavonoid extraction markedly reduced spinal cord hematoma, inflammatory cell infiltration and cavities and scars, and increased the Basso, Beattie, and Bresnahan locomotor scale scores; these effects were identical to those of methylprednisolone. Huangqin flavonoid extraction also increased immunoreactivity and expression levels of brain-derived neurotrophic factor and neurofilament protein, and reduced immunoreactivity and expression levels of CD11 b and glial fibrillary acidic protein, in the injured spinal cord. Overall, these data suggest that Huangqin flavonoid extraction can promote recovery of spinal cord injury by inducing brain-derived neurotrophic factor and neurofilament protein expression, reducing microglia activation and regulating reactive astrocytes.展开更多
BACKGROUND： Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused ...BACKGROUND： Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused on normal, not pathological, cutaneous nerves. However, laser scanning confocal microscopy results in a three-dimensional structure of the nerve fibers. OBJECTIVE： To observe quantitative and morphological differences in nerve fibers from the proliferative and mature stage in hypertrophic scars using fluorescent and confocal microscopy. DESIGN, TIME AND SETTING： Neuropathological, comparison study was conducted at the Provincial Hospital Affiliated to Shandong University, China from June 2006 to July 2007. PARTICIPANTS： Specimens were selected from 30 patients undergoing scar restoration at the Provincial Hospital Affiliated to Shandong University of China at 1 month to 23 years following wound healing. The study comprised 20 males and 10 females. The scars were fibrous lesions, erythematous, tough, confined to skin lesions, did not exhibit ulceration or infection, exhibited telangiectasia, with or without itching and pain, and were not locally treated. Samples were equally assigned to two groups according to course of disease： proliferative group （〈 6 months） and mature group （6-24 months）. Control samples were collected from full-thickness skin from donor sites （n = 10）. METHODS： Nerve fiber morphology was observed using fluorescent and confocal microscopy following immunofluorescence of the skin specimens. The microscopic images were semi-quantitatively analyzed to acquire a positive area ratio of neurofilament protein-positive nerve fibers. MAIN OUTCOME MEASURES： Morphology and positive area ratio of neurofilament protein/positive nerve fibers was measured. RESULTS： The positive area ratio of neurofilament protein-positive nerve fibers was significantly greater in the proliferative group compared to the normal control group （P 〈 0.05）. Nerve fibers were irregularly distributed and exhibited local swelling, twisting, and disconnection. However, the positive area ratio of neurofilament protein-positive nerve fibers was significantly less in the mature group compared with the normal control group （P 〈 0.05）. The nerve fibers were arranged in an orderly manner, with intact inner and stereoscopic structures similar to normal skin. CONCLUSION： Compared with mature scars, hypertrophic scars exhibited a greater number of nerve fibers, with more serious pathologies.展开更多
After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether d...After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.展开更多
P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of ne...P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.展开更多
Even though many studies have identified roles of proteasomes in axonal degeneration, the mo- lecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found e...Even though many studies have identified roles of proteasomes in axonal degeneration, the mo- lecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were sig- nificantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration.展开更多
Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy poly- urethane material was...Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy poly- urethane material was implanted in the rat C^-s epidural space to establish a rat model of chronic cervical spondylotic myelopathy. Diffusion tensor data were used to predict pathological changes. Results revealed that the fractional anisotropy value gradually decreased at 4, 24, and 72 hours and 1 week after injury in rat spinal cord, showing a time-dependent manner. Average diffusion coeffi- cient increased at 72 hours and 1 week after implantation. Hematoxylin-eosin staining and Luxol-fast-blue staining exhibited that the number of neurons in the anterior horn of the spinal cord gray matter and the nerve fiber density of the white matter gradually reduced with prolonged com- pression time. Neuronal loss was most significant at 1 week after injury. Results verified that the fractional anisotropy value and average diffusion coefficient reflected the degree of pathological change in the site of compression in rat models at various time points after chronic spinal cord compression injury, which potentially has a reference value in the early diagnosis of chronic cervical spondylotic myelopathy.展开更多
Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functiona...Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.展开更多
Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by conse...Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by consecutive intraperitoneal injections of low-dose （25 mg/kg） streptozotocin. After intragastrical perfusion of sericin for 35 days, blood glucose levels significantly declined, and the expression of neurofilament protein in the sciatic nerve and nerve growth factor in L4-6 spinal ganglion and anterior horn cells significantly increased. However, the expression of neuropeptide Y in spinal ganglion and anterior horn cells significantly decreased in model rats. These findings indicate that sericin protected the sciatic nerve and related nerve cells against injury in a rat type 2 diabetic model by upregulating the expression of neurofilament protein in the sciatic nerve and nerve growth factor in spinal ganglion and anterior horn cells, and downregulating the expression of neuropeptide Y in spinal ganglion and anterior horn cells.展开更多
文摘Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by the National Key Research&Development Program of China,Nos.2021YFC2501205(to YC),2022YFC24069004(to JL)the STI2030-Major Project,Nos.2021ZD0201101(to YC),2022ZD0211800(to YH)+2 种基金the National Natural Science Foundation of China(Major International Joint Research Project),No.82020108013(to YH)the Sino-German Center for Research Promotion,No.M-0759(to YH)a grant from Beijing Municipal Science&Technology Commission(Beijing Brain Initiative),No.Z201100005520018(to JL)。
文摘Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.
文摘Neurofilaments (NFs) were isolated from bovine spinal cord. The structure of purified NFs was studied by scanning tunneling microscopy (STM). The STM images showed that NF was composed of a long core filament and numerous sidearms flanking the rod regularly. The diameter of the rod was about 10 nm (10.2±0.8 nm). Most of the sidearms were short and the distance between two adjacent sidearms was approximately 10 nm. There were some long sidearms between two proximal core filaments. The distance between two adjacent long sidearms was 21 nm. A three-quarter-staggered fashion of native NF structure was put forward.
基金funded by the Chongqing Postdoctoral Innovative Talent Support Program[Grant No.CQBX2021008]the Chongqing Talents Project[CQYC202105043]。
文摘Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HILFN.Methods Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^(-/-)) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.Results The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilamentpositive nerve fibers in the cornu ammonis 1(CA1) and dentate gyrus(DG) hippocampal areas in wildtype mice. However, TRPV4^(-/-)mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.Conclusion TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus,which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
文摘Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of the spinal cord in some cases.A limited number of axons(20-50)can cross the bridge and re-connect the caudal stump of the spinal cord with small neurons located in the rostral stump of the spinal cord.This axonal regeneration appears to be related to the recovery of hind-limb movements after initial paralysis.The present study extends previous studies and shows that after transection of the lumbar spinal cord in lizards,a glial-connective tissue bridge that reconnects the rostral and caudal stumps of the interrupted spinal cord is formed at 11-34 days post-injury.Following an initial paralysis some recovery of hindlimb movements occurs within 1-3 months post-injury.Immunohistochemical and ultrastructural analysis for a growth associated protein 43(GAP-43)of 48-50 k Da shows that sparse GAP-43 positive axons are present in the proximal stump of the spinal cord but their number decreased in the bridge at 11-34 days post-transection.Few immunolabeled axons with a neurofilament protein of 200-220 k Da were seen in the bridge at 11-22 days post-transection but their number increased at 34 days and 3 months post-amputation in lizards that have recovered some hindlimb movements.Numerous neurons in the rostral and caudal stumps of the spinal cord were also labeled for GAP43,a cytoplasmic protein that is trans-located into their axonal growth cones.This indicates that GAP-43 biosynthesis is related to axonal regeneration and sprouting from neurons that were damaged by the transection.Taken together,previous studies that utilized tract-tracing technique to label the present observations confirm that a limited axonal re-connection of the transected spinal cord occurs 1-3 months post-injury in lizards.The few regenerating-sprouting axons within the bridge reconnect the caudal with the rostral stumps of the spinal cord,and likely contribute to activate the neural circuits that sustain the limited but important recovery of hind-limb movements after initial paralysis.The surgical procedures utilized in the study followed the regulations on animal care and experimental procedures under the Italian Guidelines(art.5,DL 116/92).
基金supported by FIS/IMSS project No.FIS/IMSS/PROT/G13/1216CGA received Beca de Excelencia en Investigación by Fundación IMSS,ACS+1 种基金JJSU received financial support from CIS/IMSSCONACy T,RPA received financial support from USC-CONACYT Postdoctoral Scholars Program
文摘Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.
基金These authors contribute equally to this work.Supported by the Hunan science fourndation(JJY2069)
文摘Objective:To investigate the morphological changes of the neuronal neurites in diabetic rabbit brain. Methods: Twenty- four New Zealand White rabbits were divided into 2 groups: control group and type Ⅱ diabetic group induced by high - carbohydrate and high- fat diet. The levels of blood sugar and insulin were detected at week 0(w0), w4, w8, w13, w18, w23 and w28. Brain tissue was stained by Nissl staining and immunolistochemistry with a specific antibody to neurofilament proteins. Result: In diabetic rabbits, the amount of large pyramidal neuron was significantly reduced, and neuronal neurites became swollen, whorled, disrupted and changed in caliber. In hippocampus CA1 region neurofilament staining was very weak. Conclusion: Neurotoxicity of chronic hyperglycemia might be relevant to vascular chronic complications, which affected the expression of NF and led to neurophysiological and structural changes in the brain of rabbits with type Ⅱ diabetes.
基金supported by the National Natural Science Foundation of China, No. 30872609
文摘Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.
基金supported by grants from the National Natural Science Foundation of China,No.31300812 and No.31371218
文摘Cytoskeletal proteins are involved in neuronal survival.Brain-derived neurotrophic factor can increase expression of cytoskeletal proteins during regeneration after axonal injury.However,the effect of neural stem cells genetically modified by brain-derived neurotrophic factor transplantation on neuronal survival in the injury site still remains unclear.To examine this,we established a rat model of traumatic brain injury by controlled cortical impact.At 72 hours after injury,2 × 10~7 cells/m L neural stem cells overexpressing brain-derived neurotrophic factor or naive neural stem cells（3 m L） were injected into the injured cortex.At 1–3 weeks after transplantation,expression of neurofilament 200,microtubule-associated protein 2,actin,calmodulin,and beta-catenin were remarkably increased in the injury sites.These findings confirm that brain-derived neurotrophic factor-transfected neural stem cells contribute to neuronal survival,growth,and differentiation in the injury sites.The underlying mechanisms may be associated with increased expression of cytoskeletal proteins and the Wnt/β-catenin signaling pathway.
基金supported by the National Natural Science Foundation of China,No.81403278(to QZ)the Natural Science Foundation of Shaanxi Province of China,No.2017JM8058(to QZ)the Shaanxi Administration of Traditional Chinese Medicine in China,No.15-ZY038(to QZ)
文摘Flavonoids from Huangqin（dried roots of Scutellaria baicalensis Georgi） have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9-10 spinal cord segments of rats were damaged using Allen＇s method to establish a rat spinal cord injury model. Before model establishment, Huangqin flavonoid extraction（12.5 g/kg） was administered intragastrically for 1 week until 28 days after model establishment. Methylprednisolone（30 mg/kg） was injected into the tail vein at 30 minutes after model establishment as a positive control. Basso, Beattie, and Bresnahan locomotor scale scores were used to assess hind limb motor function. Hematoxylin-eosin staining was used to detect pathological changes in the injured spinal cord. Immunofluorescence and western blot assays were performed to measure immunoreactivity and expression levels of brain-derived neurotrophic factor, neuronal marker neurofilament protein, microglial marker CD11 b and astrocyte marker glial fibrillary acidic protein in the injured spinal cord. Huangqin flavonoid extraction markedly reduced spinal cord hematoma, inflammatory cell infiltration and cavities and scars, and increased the Basso, Beattie, and Bresnahan locomotor scale scores; these effects were identical to those of methylprednisolone. Huangqin flavonoid extraction also increased immunoreactivity and expression levels of brain-derived neurotrophic factor and neurofilament protein, and reduced immunoreactivity and expression levels of CD11 b and glial fibrillary acidic protein, in the injured spinal cord. Overall, these data suggest that Huangqin flavonoid extraction can promote recovery of spinal cord injury by inducing brain-derived neurotrophic factor and neurofilament protein expression, reducing microglia activation and regulating reactive astrocytes.
文摘BACKGROUND： Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused on normal, not pathological, cutaneous nerves. However, laser scanning confocal microscopy results in a three-dimensional structure of the nerve fibers. OBJECTIVE： To observe quantitative and morphological differences in nerve fibers from the proliferative and mature stage in hypertrophic scars using fluorescent and confocal microscopy. DESIGN, TIME AND SETTING： Neuropathological, comparison study was conducted at the Provincial Hospital Affiliated to Shandong University, China from June 2006 to July 2007. PARTICIPANTS： Specimens were selected from 30 patients undergoing scar restoration at the Provincial Hospital Affiliated to Shandong University of China at 1 month to 23 years following wound healing. The study comprised 20 males and 10 females. The scars were fibrous lesions, erythematous, tough, confined to skin lesions, did not exhibit ulceration or infection, exhibited telangiectasia, with or without itching and pain, and were not locally treated. Samples were equally assigned to two groups according to course of disease： proliferative group （〈 6 months） and mature group （6-24 months）. Control samples were collected from full-thickness skin from donor sites （n = 10）. METHODS： Nerve fiber morphology was observed using fluorescent and confocal microscopy following immunofluorescence of the skin specimens. The microscopic images were semi-quantitatively analyzed to acquire a positive area ratio of neurofilament protein-positive nerve fibers. MAIN OUTCOME MEASURES： Morphology and positive area ratio of neurofilament protein/positive nerve fibers was measured. RESULTS： The positive area ratio of neurofilament protein-positive nerve fibers was significantly greater in the proliferative group compared to the normal control group （P 〈 0.05）. Nerve fibers were irregularly distributed and exhibited local swelling, twisting, and disconnection. However, the positive area ratio of neurofilament protein-positive nerve fibers was significantly less in the mature group compared with the normal control group （P 〈 0.05）. The nerve fibers were arranged in an orderly manner, with intact inner and stereoscopic structures similar to normal skin. CONCLUSION： Compared with mature scars, hypertrophic scars exhibited a greater number of nerve fibers, with more serious pathologies.
基金supported by the Xinjiang Production and Construction Corps Doctoral Fund of China,No.2014BB020
文摘After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.
基金financially supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HM046(to ZCZ),ZR2015HL113(to XJD),and ZR2014HL101(to XYW)the Science and Technology Development Project of Taian City of China,No.2015NS2183(to XJD)
文摘P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.
基金supported by research funds from Dong-A University,South Korea
文摘Even though many studies have identified roles of proteasomes in axonal degeneration, the mo- lecular mechanisms by which axonal injury regulates proteasome activity are still unclear. In the present study, we found evidence indicating that extracellular calcium influx is an upstream regulator of proteasome activity during axonal degeneration in injured peripheral nerves. In degenerating axons, the increase in proteasome activity and the degradation of ubiquitinated proteins were sig- nificantly suppressed by extracellular calcium chelation. In addition, electron microscopic findings revealed selective inhibition of neurofilament degradation, but not microtubule depolymerization or mitochondrial swelling, by the inhibition of calpain and proteasomes. Taken together, our findings suggest that calcium increase and subsequent proteasome activation are an essential initiator of neurofilament degradation in Wallerian degeneration.
基金supported by the Natural Science Foundation of Guangdong Province of China,No.S2011010004843the National Natural Science Foundation of China,No.30770679,31070941,30570572the Major Basic Research of Ministry of Science and Technology of China(973 Project),No.2010CB530004
文摘Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy poly- urethane material was implanted in the rat C^-s epidural space to establish a rat model of chronic cervical spondylotic myelopathy. Diffusion tensor data were used to predict pathological changes. Results revealed that the fractional anisotropy value gradually decreased at 4, 24, and 72 hours and 1 week after injury in rat spinal cord, showing a time-dependent manner. Average diffusion coeffi- cient increased at 72 hours and 1 week after implantation. Hematoxylin-eosin staining and Luxol-fast-blue staining exhibited that the number of neurons in the anterior horn of the spinal cord gray matter and the nerve fiber density of the white matter gradually reduced with prolonged com- pression time. Neuronal loss was most significant at 1 week after injury. Results verified that the fractional anisotropy value and average diffusion coefficient reflected the degree of pathological change in the site of compression in rat models at various time points after chronic spinal cord compression injury, which potentially has a reference value in the early diagnosis of chronic cervical spondylotic myelopathy.
基金supported by a grant from the Science and Technology Development Program of Jilin Province of China,No.2011084
文摘Previous studies have shown that the neurite growth inhibitor Nogo-A can cause secondary neural damage by activating Rho A. In the present study, we hypothesized that electroacupuncture promotes neurological functional recovery after spinal cord injury by inhibiting Rho A expression. We established a rat model of acute spinal cord injury using a modification of Allen＇s method. The rats were given electroacupuncture treatment at Dazhui（Du14）, Mingmen（Du4）, Sanyinjiao（SP6）, Huantiao（GB30）, Zusanli（ST36） and Kunlun（BL60） acupoints with a sparsedense wave at a frequency of 4 Hz for 30 minutes, once a day, for a total of 7 days. Seven days after injury, the Basso, Beattie and Bresnahan（BBB） locomotor scale and inclined plane test scores were significantly increased, the number of apoptotic cells in the spinal cord tissue was significantly reduced, and Rho A and Nogo-A m RNA and protein expression levels were decreased in rats given electroacupuncture compared with rats not given electroacupuncture. Four weeks after injury, pathological tissue damage in the spinal cord at the site of injury was alleviated, the numbers of glial fibrillary acidic protein- and neurofilament 200-positive fibers were increased, the latencies of somatosensory-evoked and motor-evoked potentials were shortened, and their amplitudes were increased in rats given electroacupuncture. These findings suggest that electroacupuncture treatment reduces neuronal apoptosis and decreases Rho A and Nogo-A m RNA and protein expression at the site of spinal cord injury, thereby promoting tissue repair and neurological functional recovery.
文摘Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by consecutive intraperitoneal injections of low-dose （25 mg/kg） streptozotocin. After intragastrical perfusion of sericin for 35 days, blood glucose levels significantly declined, and the expression of neurofilament protein in the sciatic nerve and nerve growth factor in L4-6 spinal ganglion and anterior horn cells significantly increased. However, the expression of neuropeptide Y in spinal ganglion and anterior horn cells significantly decreased in model rats. These findings indicate that sericin protected the sciatic nerve and related nerve cells against injury in a rat type 2 diabetic model by upregulating the expression of neurofilament protein in the sciatic nerve and nerve growth factor in spinal ganglion and anterior horn cells, and downregulating the expression of neuropeptide Y in spinal ganglion and anterior horn cells.
