Objective To evaluate proton MR spectroscopy (1H-MRS) for detection of the motor cortex and adjacent brain in amyotrophic lateralsclerosis (ALS) patients with apparent upper motor neuron involvement after olfactory ensheathing cells(OECs) transplantation. Methods From December 2004 to February 2005, 7 patients with clinically definite ALS who could safely undergo MRS were admitted into the perspective study. The neurological status, ALS functional rating scale (ALSFRS), EMG, and 1H-MRS taken before and 2 weeks after operationswere carefully analyzed. The NAA/Cr and Cho/Cr ratios were measured in the cerebral peduncle,genu and posterior limb of the internal capsule, corona radiata and precentral gyrus. Results The ALSFRS in 2 cases mproved obviously whose ALSFRS increased from 30 to 33 and from 29 to 34 respectively. And 5 cases remained stable 2 weeks after OECs transplantation. Statistical analyses for all seven cases showed both theNAA/Cr and Cho/Cr ratios decreased, but in the two cases with ALSFRS improvement the NAA/Cr increased in the certain anatomic position which confirmed the neurological and EMG findings. Conclusion The proton MR spectroscopy is a suitablenoninvasive measure for ALS evaluation. The preliminary study suggests that twoof the seven ALS cases improved apparently shortterm after OECs transplantation. More patients are required for the clinical study and longer followup duration is needed for future research.
Objective To introduce a new functional self-assessment scale of amyotrophic lateral sclerosis (ALS). Methods By comparing current different ALS functional scales and combining relative cl inical experience and numeric pain intensity scale, ALS self-assessment scale was set down by International Association of Neural Restoration. Results ALS self-assessment scale included 3 categories with 18 items, adopting 10 points grading system, namely 10 was defined as the normal, 0 as the worst, and the total scores was 180. This scale included: ① Bulbus medullae function: speech, swallowing, sal ivation, and tongue extension. ② Limbs function: left arm movement, left hand movement, right arm movement, right hand movement, left leg movement, right leg movement, trunk movement, head-up, walking, and cl imbing stairs. ③ Others: breathing, muscular tone, pain, and muscle discomfort. Conclusion ALS self-assessment scale is specifically designed for ASL patients. It can evaluate patient’s function comprehensively and is simple and convenient, consuming less time.
Objective To investigate the effect of exogenous erythropoietin (EPO) on the denervated muscle atrophy. Methods Twenty-four SD male rats, weighting 200-220 g were made the models of denervated gastrocnemius muscle after sciatic nerves were transected under the piriform muscle at the right lower leg, and were randomly divided into two groups (n=12). rhEPO (2 500 U/kg) was injected daily into the denervated gastrocnemius muscle in EPO group, and normal sal ine was injected into the denervated gastrocnemius muscle in control group. To observe the general state of health of the experimental animal, the muscle wet weight, the muscle cell diameter, the cross section area, the protein amount, thepercentage of the apoptotic muscle cells, and the Na+-K+-ATPase and Ca2+-ATPase activities were measured 2 and 4 weeks after operation. Results All experimental animals were survived during experiment without cut infection, and all animals could walk with pull ing the right knee. At 4 weeks after operation, 7 cases showed ulcer in the right heel, inculding 5 in the control group and 2 in the EPO group. At 2 and 4 weeks after operation, the muscle wet weight in EPO group was (885.59 ± 112.35) and (697.62 ± 94.74) g, respectively; in control group, it was (760.63 ± 109.05) and (458.71 ± 58.76) g, respectively; indicating significant differences between two groups (P lt; 0.01). The protein amount in EPO group was (77.37 ± 5.24) and (66.37 ± 4.87) mg/mL, respectivly；in control group, it was (65.39 ± 4.97) and (54.62 ± 6.32) mg/mL；indicating significant differences between two groups (P lt; 0.01). At 2 and 4 weeks after operation, the myofibrillar shapes were nearly normal in EPO group while there were muscle fiber atrophy, some collapse and obviously hyperblastosis between muscle bundle. There were significant differences in the muscle cell diameter and the cross section between two groups (P lt; 0.01). However, the percentage of the apoptotic muscle cells was 11.80% ± 1.74% and 28.47% ± 1.81% in control group, respectively, which was significantly smaller than that in EPO group (21.48% ± 2.21% and 55.89% ± 2.88%, P lt; 0.01). At 2 and 4 weeks after operation, Na+-K+-ATPaseand Ca2+-ATPase activities in EPO group were higher than those in control group (P lt; 0.01). Conclusion EPO can delay the denervated muscle atrophy.
Duchenne muscular dystrophy is an X-linked inherited progressive degenerative muscle disease caused by mutations in the dystrophin gene, and is one of the most common progressive muscular dystrophies. We will review the selection of genetic diagnosis methods for Duchenne muscular dystrophy, the selection of experimental animal models, and treatment for the primary cause (including gene replacement therapy, exon skipping therapy, genome editing, stop codon read-through therapy, and stem cell therapy), the treatment of secondary pathological reactions and methods of assessing disease progression. The purpose is to enrich clinicians’ knowledge of the disease and provide a reference and help for the clinical diagnosis and treatment of Duchenne muscular dystrophy.
The translation and translation regulation of RNA in eukaryotic cells have a significant impact on cellular gene expression and maintenance of proteomic homeostasis. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper and lower motor neurons and leads to muscle weakness and atrophy. More and more studies have found RNA translation abnormalities in ALS. This article provides an overview of RNA translation and regulation in eukaryotic cells under physiological and stress conditions, and explores the relationship between four different ALS-related genes and translation abnormalities, providing new ideas for the treatment of ALS.
Objective To determine whether transplanting olfactory ensheathing cells (OECs) is effective in controlling or reversing the deterioration caused by amyotrophic lateral sclerosis (ALS). Methods Between February 2003 and April 2006, 327 patients (241 males and 86 females) with probable or definite ALS (diagnosed according to the El Escorial criteria) received the OECs transplantation. Their ages ranged from 20 to 84 years (51.6±11.1 years). The duration of symptoms before surgical treatment was 4-8 months to 13 years (2.9±2.0 years). OECs were cultured and injected into pathological regions of the spinal cord and/or bilateral corona radiata of the brain; the patients were divided into three groups, group A (cord only,n=29), group B (cord and brain,n=6), and group C (brain only,n=292) based on the transplant sites. Results The patient’s neurological function was assessed both before and at 4 weeks after transplantation by using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) of the ALS CNTF Treatment Study (ACTS). The scores were increased from 17.2±8.6 preoperation to 20.1±9.7 postoperation in group A (P＜0.05),from 24.2±6.8to 25.7±6.6 (P＞0.05) in group B, and from 20.3±8.6 to 22.0±9.4 (P＜0.001) in group C.There were no significant difference in increased ALSFRS scores among the threegroups (P＞0.05). The total improvement rate of neurological function was 77.1% (252/327). The result of electromyographic examination showed that spontaneouspotential diminished and/or disappeared, the amplitude of the motor unit actionpotential decreased remarkably and the numbers of motor unit action potential greatly increased in 261 cases (79.8%). Sixteen patients (4.9%) experienced thevarious complications including headache, shortterm fever, seizure attack, central nerve system infection, pneumonia, respiratory failure, urinary tract infection, heart failure, and possible pulmonary embolism; of them, there were 4 deaths(1.2%). Conclusion These preliminary results suggest that the OECs transplantation is effective in controlling or reversing the physiological deterioration caused by ALS.
Objective To investigate the preventive and therapeutic effects and the mechanisms of pyrrol idine dithiocarbamate (PDTC) on the atrophy of denervated skeletal muscle. Methods Thirty adult Wistar rats of either gender, weighing (200 ± 10) g were randomly divided into 3 groups: group A (n=6, control group), group B (n=12, denervation group), and group C (n=12, PDTC treatment group). The sciatic nerves of the rats were only exposed without cutting off in group A, and the rats were made denervated gastrocnemius models in groups B and C. PDTC of 100 mg/(kg•d) was injected peritoneally in group C and an intraperitoneal injection of the same amount normal sal ine was given in group B. After 14 and 28 days, the gastrocnemius was harvested to measure the ratio of muscle wet weight; the levels of nuclear factor of κB (NF-κB)p65 protein and the opening of the mitochondrial permeabil ity transition pore (MPTP) in the gastrocnemius were detectedrespectively by Western blot and laser confocal scanning microscope; and the apoptotic cells in atrophic muscle were measured with TUNEL. Results The ratio of muscle wet weight in group A was 1.039 ± 0.115, and it significantly decreased in groups B and C (P lt; 0.05); after 14 and 28 days of operation, the ratio of muscle wet weight in group C significantly increased when compared with those in group B (P lt; 0.05). The expression of NF-κB p65 protein in group A was 0.224 ± 0.041; the expressions of NF-κB p65 in groups B and C significantly increased when compared with that in group A (P lt; 0.05); however, the expression of NF-κB p65 in group C was significantly lower than that in group B (P lt; 0.05). The MPTP fluorescence intensity in group A was 31.582 ± 1.754; the MPTP fluorescence intensity was significantly lower in groups B and C than in group A (P lt; 0.05), and the MPTP fluorescence intensity in group C was significantly higher than that in group B (P lt; 0.05). The rate of apoptosis in group A was 4.542% ± 0.722%; after 14 and 28 days of operation, the rates of apoptosis significantly increased when compared groups B and C with group A, and signiticantly decreased when compared group C with group B (P lt; 0.05). Conclusion PDTC can retard denervated skeletal muscle atrophy, and the effect may have a relationship with its inhibition on NF-κB, the opening of the MPTP, and the ratio of apoptosis.
Objective To study the effect of the competitive inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (LNAME) on thedenervated muscle atrophy. Methods A model of the denervated gastrocnemius atthe right lower limb was established in 36 SD adult rats. The rats were randomly divided into two groups: the L-NAMEgroup (Group A) and the control group(Group B). L-NAME 10 mg/ kg daily was injected into the denervated gastrocnemius inGroup A, and normal saline was injected into the denervated gastrocnemius in Group B. At 2, 4 and 8 weeks after operation, the rate of the muscle wet weight preservation, the cross section area of the myocyte, the protein amount, and the percentage of the apoptotic muscle cells were measured respectively and the ultramicrostructure of the myocyte was observed. Results At 2 and 4 weeks after operation, the rate of the muscle wet weight preservation, the cross section area of themyocyte, and the protein amount were significantly greater in Group A than in Group B; however, the percentage of the apoptotic muscle cells was significantly smaller in Group A than in Group B. The observation of the ultramicrostructure of themyocyte showed that an injection of L-NAME could protect the ultramicrostructure of themyocyte. At 8 weeks after operation, there was no significant difference between the two groups in the abovementioned parameters. Conclusion The nitric oxide synthase inhibition can delay the denervated muscle atrophy.
Objective To investigate the effect of the neuromuscular pedicle transplantation in prevention against atrophy in the denervated muscle. Methods Fortyeight SD rats were used to establish the right side tibialis anterior muscle denervation model. The long peroneal muscle neuromuscular pedicle was made as a treatment in 12 rats (Group A); the nerve shaft embedding was used in 12 rats (Group B); no treatment was used in 12 rats(Group C); the remaining 12 rats were used as normal controls (Group D). The gait analysis, electromyogram，muscle wet weight, and muscle fiber crosssectional area were used to determine and compare the effect of the operation at 6 and 12 weeks postoperatively. ResultsAt 6 weeks postoperatively, the parameters tested in Group A about the gait analysis (peroneal function index, PFI, －47.20±12.30), electromyogram, muscle wet weight (0.384 0±0.024 6 g)and muscle fiber cross-sectional area (1 040.98±120.54 μm2) were significantly better than those in Group C (PFI, -114.40±14.84; muscle wet weight, 0.173 0±0.019 1 g; muscle fiber cross-sectional area, 585.08±182.93 μm2,Plt;0.05), and the final two parameters were significantly better than those in Group B (0.294 0±0.056 4 g,763.92±82.68 μm2,Plt;0.05). At 12 weeks postoperatively, the musclefiber crosssectional area in Group A(1 360.10±261.45 μm2) had no significant difference from that in Group D (1 544.57±266.92 μm2，Pgt;0.05)，and most of the parameters tested in Group A were better than those in Groups B and C. Conclusion Neuromuscular pedicle transplantation has an excellent effect in prevention against atrophy in the denervated muscle, and the effect of neuromuscular pedicle transplantation is better than that of the nerve shaft embedding.