Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the micros...Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T_(10) spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord(R = 0.919, P = 0.027), white matter(R = 0.932, P = 0.021), and gray matter(R = 0.882, P = 0.048). Additionally, the other parameters had almost no correlation with the score(P 〉 0.05). In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.展开更多
Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cle...Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.展开更多
Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Seleniu...Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.展开更多
OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China...OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms(the Medical Subject Headings) such as "myelotomy", "spinal cord injuries", "rats", "randomized controlled trial" and all related entry terms were searched. DATA SELECTION: Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software(version 5.3) was used for data processing. The χ^2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES: Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS: Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees(moderate or severe). The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group(weighted mean difference(WMD) = 0.60; 95% confidence interval(CI): 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI: 1.56–2.64; P 〈 0.001; WMD = 2.65; 95% CI: 1.73–3.57; P 〈 0.001; WMD = 1.66; 95% CI: 0.80–2.52; P 〈 0.001; WMD = 2.09; 95% CI: 0.92–3.26, P 〈 0.001; WMD = 2.25; 95% CI: 1.06–3.44, P 〈 0.001). The overall heterogeneity was high(I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%). The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group(WMD = 0.91, 95% CI: 0.52–1.3, P 〈 0.001; WMD = 2.10; 95% CI: 1.56–2.64, P 〈 0.001; WMD = 2.65; 95% CI: 1.73–3.57, P 〈 0.001; WMD = 2.50, 95% CI: 1.72–3.28, P 〈 0.001; WMD = 3.29, 95% CI: 2.21–4.38, P 〈 0.001; WMD = 3.27; 95% CI: 2.31–4.23, P 〈 0.001). The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury(P = 0.75; P = 0.92). CONCLUSION: To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.展开更多
Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure ...Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I(steep rise) 1–7 hours, stage Ⅱ(steady rise) 8–38 hours, and stage Ⅲ(descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages Ⅱ and Ⅲ of spinal cord injury.展开更多
With the popularity of urine flow dynamic monitoring and indwelling catheter technologies in animal experiments,the urethral catheterization has become a common technique in scientific research.The miniature pig is co...With the popularity of urine flow dynamic monitoring and indwelling catheter technologies in animal experiments,the urethral catheterization has become a common technique in scientific research.The miniature pig is considered as one of the major animal species used in scientific research and is increasingly being used as an alternative to a dog or monkey as the nonrodent species of choice in the preclinical toxicological testing of pharmaceuticals.[1] Since there are three acute angles bending in the urethra of the male miniature pig,and the end of the penis head is cork-screw shaped,it is difficult to implement routine urethral catheterization in male miniature pigs.Currently,researchers usually implement bladder colostomies or dissections in male miniature pigs,while transurethral urethral catheterization can be implemented in female miniature pigs.According to the existing reports,implementing transurethral urethral catheterization in female miniature pigs is seldom seen.[2] We chose 3-month-old female Bama miniature pigs in our experiments and employ the following methods:first,use a "V"-shaped platform with an angle of about 30° to the horizontal plane;second,utilize a pediatric laryngoscope for deep lighting;third,bend the lower limbs and press down to the ventral side.Satisfactory results through transurethral urethral catheterization were achieved in the end.展开更多
基金supported by the National Natural Science Foundation of China,No.81272164the Special Fund for Basic Scientific Research of Central Public Research Institutes in China,No.2015CZ-6,2016CZ-4+2 种基金the Beijing Institute for Brain Disorders in China,No.201601,0000-100031the Supporting Program of the “Twelve Five-year Plan” for Science&Technology Research of China,No.2012BAI34B02a grant from the Ministry of Science and Technology of China,No.2015CB351701
文摘Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T_(10) spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord(R = 0.919, P = 0.027), white matter(R = 0.932, P = 0.021), and gray matter(R = 0.882, P = 0.048). Additionally, the other parameters had almost no correlation with the score(P 〉 0.05). In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81870979(to JJL),No.81271366(to MLY)the National Key R&D Program of China,No.2018YFF0301104(to JJL)+4 种基金the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2018CZ-1(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2018ZX-30(to FG)the Scientific Research Foundation of CRRC,No.2012C-1(to JJL)the Major Science and Technology Project of Beijing of China,No.D161100002816004(to JJL)the Special Capital Health Research and Development of China,No.2018-1-6011(to JJL)
文摘Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.
基金supported by the National Natural Science Foundation of China, No.81870979(to JJL)the Scientific Research Foundation of China Rehabilitation Research Center, No.2020-02(to JJL)the Natural Science Foundation of Changsha, No.kq2014285(to YXC)
文摘Ferroptosis is a recently discovered form of iron-dependent cell death,which occurs during the pathological process of various central nervous system diseases or injuries,including secondary spinal cord injury.Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis.However,whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood.In this study,we injected sodium selenite(3μL,2.5μM)into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling.We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal.Furthermore,sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4,promoted the survival of neurons and oligodendrocytes,inhibited the proliferation of astrocytes,and promoted the recovery of locomotive function of rats with spinal cord injury.These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.
基金supported by the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2015CZ-6,2016CZ-4a grant from the Beijing Institute for Brain Disorders,No.201601
文摘OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms(the Medical Subject Headings) such as "myelotomy", "spinal cord injuries", "rats", "randomized controlled trial" and all related entry terms were searched. DATA SELECTION: Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software(version 5.3) was used for data processing. The χ^2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES: Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS: Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees(moderate or severe). The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group(weighted mean difference(WMD) = 0.60; 95% confidence interval(CI): 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI: 1.56–2.64; P 〈 0.001; WMD = 2.65; 95% CI: 1.73–3.57; P 〈 0.001; WMD = 1.66; 95% CI: 0.80–2.52; P 〈 0.001; WMD = 2.09; 95% CI: 0.92–3.26, P 〈 0.001; WMD = 2.25; 95% CI: 1.06–3.44, P 〈 0.001). The overall heterogeneity was high(I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%). The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group(WMD = 0.91, 95% CI: 0.52–1.3, P 〈 0.001; WMD = 2.10; 95% CI: 1.56–2.64, P 〈 0.001; WMD = 2.65; 95% CI: 1.73–3.57, P 〈 0.001; WMD = 2.50, 95% CI: 1.72–3.28, P 〈 0.001; WMD = 3.29, 95% CI: 2.21–4.38, P 〈 0.001; WMD = 3.27; 95% CI: 2.31–4.23, P 〈 0.001). The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury(P = 0.75; P = 0.92). CONCLUSION: To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.
基金supported by the National Natural Science Foundation of China,No.81272164(to JJL)the Special Fund for Basic Scientific Research of Central Public Research Institutes in China,No.2016CZ-4(to JJL),2018CZ-1(to JJL)+1 种基金the Beijing Institute for Brain Disorders in China,No.0000-100031(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2017ZX-22,2017ZX-20(to JJL)
文摘Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I(steep rise) 1–7 hours, stage Ⅱ(steady rise) 8–38 hours, and stage Ⅲ(descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages Ⅱ and Ⅲ of spinal cord injury.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 81271366).
文摘With the popularity of urine flow dynamic monitoring and indwelling catheter technologies in animal experiments,the urethral catheterization has become a common technique in scientific research.The miniature pig is considered as one of the major animal species used in scientific research and is increasingly being used as an alternative to a dog or monkey as the nonrodent species of choice in the preclinical toxicological testing of pharmaceuticals.[1] Since there are three acute angles bending in the urethra of the male miniature pig,and the end of the penis head is cork-screw shaped,it is difficult to implement routine urethral catheterization in male miniature pigs.Currently,researchers usually implement bladder colostomies or dissections in male miniature pigs,while transurethral urethral catheterization can be implemented in female miniature pigs.According to the existing reports,implementing transurethral urethral catheterization in female miniature pigs is seldom seen.[2] We chose 3-month-old female Bama miniature pigs in our experiments and employ the following methods:first,use a "V"-shaped platform with an angle of about 30° to the horizontal plane;second,utilize a pediatric laryngoscope for deep lighting;third,bend the lower limbs and press down to the ventral side.Satisfactory results through transurethral urethral catheterization were achieved in the end.