The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was...The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.展开更多
The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth...The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.展开更多
For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein th...For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.展开更多
Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-met...Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
Metformin,a first-line drug for type-2 diabetes,has been shown to improve locomotor recovery after spinal cord injury.However,there are studies reporting no beneficial effect.Recently,we found that high dose of metfor...Metformin,a first-line drug for type-2 diabetes,has been shown to improve locomotor recovery after spinal cord injury.However,there are studies reporting no beneficial effect.Recently,we found that high dose of metformin(200 mg/kg,intraperitoneal)and acute phase administration(immediately after injury)led to increased mortality and limited locomotor function recovery.Consequently,we used a lower dose(100 mg/kg,i.p.)metformin in mice,and compared the effect of immediate administration after spinal cord injury(acute phase)with that of administration at 3 days post-injury(subacute phase).Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale(BMS)scoring.Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site.Furthermore,metformin treatment at the subacute phase reduced neutrophil infiltration.These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin.These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection.This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch(approval No.1008041C)in 2010.展开更多
Tail autotomy is a defense mechanism used by many lizards to evade predators, but it entails costs. We used the oriental leaf-toed gecko Hemidactylus bowringii as a model animal to evaluate locomotor costs of tail aut...Tail autotomy is a defense mechanism used by many lizards to evade predators, but it entails costs. We used the oriental leaf-toed gecko Hemidactylus bowringii as a model animal to evaluate locomotor costs of tail autotomy. We removed the tail about 5 mm from the tail base from each of the experimental geckos(adult males) initially having intact tails. Tailless experimental geckos and tailed control geckos were measured for overall speed and sprint speed in both vertical and horizontal directions. Overall speed and sprint speed did not differ between tailless and tailed geckos. The influence of locomotor direction on both overall speed and sprint speed was significant, with horizontal speed being greater than vertical speed. The interaction between tail condition and locomotor direction was not significant in overall speed, but was significant in sprint speed. Tailless geckos had faster vertical sprint speed than the tailed individuals. Of the 130 field-caught adults, 59 had previously lost their tails, with most(about 61%) of them shedding their tails near the tail base. Neither the proportion of geckos with tail autotomy nor the frequency distribution of locations of the tail break differed between the sexes. Our data show that tail loss of H. bowringii occurs frequently in nature. However, tail loss does not incur locomotor costs in this gecko.展开更多
The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological condition...The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4- chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nudeotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.展开更多
We studied the locomotor behaviour of white-headed langurs Trachypithecus leucocephalus and Francois' langurs T.francoisi to test two hypotheses: (1) these monkeys have evolved locomotor ability to support their a...We studied the locomotor behaviour of white-headed langurs Trachypithecus leucocephalus and Francois' langurs T.francoisi to test two hypotheses: (1) these monkeys have evolved locomotor ability to support their activities on limestone hills, and (2) Francois' langurs have evolved more diverse locomotor skills than white-headed langurs. Data were collected from 1996 - 1998 and in 2005 in Fusui Nature Reserve, Guangxi, and showed that the two species had similar locomotor types, but Francois' langurs had more locomotor modes (26) than white-headed langurs (12). Quadrupedal walking and leaping were two major types, and white-headed langurs were more arboreal than Francois' langurs. We suggest that, while keeping their ancestral locomotor types, the two species have evolved new types allowing them to live on limestone cliffs. Compared to white-headed langurs, Francois' langurs have more diverse locomotor modes that probably have allowed them to live in more habitat types. As an evolutionary outcome, Francois' langurs have a larger distribution range .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
Objective:To evaluate the neuroprotective effects of the organic components of scallop shells(scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibe...Objective:To evaluate the neuroprotective effects of the organic components of scallop shells(scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5,10-imine(MK801).Methods:Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test,the Morris water maze test,and the open field test.Results:Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test.Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex.Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine.Scallop shell extract also suppressed the increase in locomotor activity induced by MK801.Conclusions:Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion.展开更多
Animals have evolved a variety of behavior patterns to adapt to the environment. Motion-capture technology is utilized to quantify and characterize locomotor behaviors to reveal the mechanisms of animal motion. In the...Animals have evolved a variety of behavior patterns to adapt to the environment. Motion-capture technology is utilized to quantify and characterize locomotor behaviors to reveal the mechanisms of animal motion. In the capture of flexible, small animals with complex locomotor behaviors, the markers interfere with each other easily, and the motion forms(bending, twisting) of the moving parts are obviously different;thus, it is a great challenge to realize accurate quantitative characterization of complex locomotor behaviors. The correlation between the marker properties, including the size and space length, and the precision of the system are revealed in this paper, and the effects of diverse marker shapes on the capturing accuracy of the captured objects in different motion forms were tested. Results showed that the precision of system is significantly improved when the ratio of the space length to the diameter of the markers is larger than four;for the capture of the spatial twisting motion of the flexible object, the hexagon markers had the lowest spatial lost-marker rate relative to the circle, triangle, and square. Customized markers were used to capture the locomotor behavior of the gecko-inspired robot(rigid connection) and the gecko(flexible connection). The results showed that this marking technology can achieve high accuracy of motion capture for geckos(the average deviation was approximately 0.32 mm, and the average deviation’s variation rate was approximately 0.96%). In this paper, the marking technology for the motion capture of flexible, small animals with complex motion is proposed;it can effectively improve the system precision as well as the capture accuracy, and realize the quantitative characterization of the complex motion of flexible, small objects. It provides a reliable technical means to deeply study the evolution of the motion function of small animals and advance systematic research of motion-capture technology.展开更多
This study sought to elucidate the changes of nuclear factor kappa B (NF-KB) expression and locomotor function of hind limb after subdural injection of BMS-345541 was applied in rats with acute spinal cord injury. T...This study sought to elucidate the changes of nuclear factor kappa B (NF-KB) expression and locomotor function of hind limb after subdural injection of BMS-345541 was applied in rats with acute spinal cord injury. The results indicated that BMS-345541 treatment reduced the expression of NF-kB at 24 hours after injury, compared with normal saline-treated rats. This treatment also led to a significant improvement in locomotor functional recovery at 14 days after injury. Overall, the findings demonstrated that BMS-345541 significantly ameliorated spinal cord injury-induced hind limb dysfunction by inhibiting the expression of NF-kB after spinal cord injury.展开更多
Oscillating field stimulation(OFS)is a potential method for treating spinal cord injury.Although it has been used in spinal cord injury(SCI)therapy in basic and clinical studies,its underlying mechanism and the correl...Oscillating field stimulation(OFS)is a potential method for treating spinal cord injury.Although it has been used in spinal cord injury(SCI)therapy in basic and clinical studies,its underlying mechanism and the correlation between its duration and nerve injury repair remain poorly understood.In this study,we established rat models of spinal cord contusion at T10 and then administered 12 weeks of OFS.The results revealed that effectively promotes the recovery of motor function required continuous OFS for more than 6 weeks.The underlying mechanism may be related to the effects of OFS on promoting axon regeneration,inhibiting astrocyte proliferation,and improving the linear arrangement of astrocytes.This study was approved by the Animal Experiments and Experimental Animal Welfare Committee of Capital Medical University(supplemental approval No.AEEI-2021-204)on July 26,2021.展开更多
Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic ...Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates:a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.展开更多
There are no reports on the effect of amphetamine on female WKY circadian activity pattern. The objective of this study is to investigate whether repeated daily exposure to the psychostimulant amphetamine alters the l...There are no reports on the effect of amphetamine on female WKY circadian activity pattern. The objective of this study is to investigate whether repeated daily exposure to the psychostimulant amphetamine alters the locomotor circadian rhythm activity patterns of female adult Wistar-Kyoto (WKY) rats. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12 h light/dark cycle in an open field cage. After 5 to 7 days of acclimation, 11 days of consecutive non-stop recordings began. On experimental day 1, all groups were given an injection of saline. On experimental days 2 to 7, the experimental group was injected with 0.6 mg/kg amphetamine and the control group with saline followed by a washout phase from experimental day 8 to 10, and amphetamine re-challenge or saline on experimental day 11 similar to experimental day 2. Locomotor movements were determined using a computerized animal activity monitoring system, and cosine statistical analysis was used to fit a24-hour curve to the activity pattern. The horizontal activity (HA), total distance (TD), number of stereotypy (NOS), and stereotypical movements (SM) were analyzed for alterations in the circadian rhythm activity patterns. The data demonstrated that chronic amphetamine administration alters the mesor parameter of the circadian rhythm activity patterns, indicating that chronic amphetamine treatment exerts long term effects on these rats.展开更多
Previous social experience may affect subsequent behavior. It was shown by other authors that Drosophila melanogaster males kept individually are more aggressive and sexually active than males kept in a group. In the ...Previous social experience may affect subsequent behavior. It was shown by other authors that Drosophila melanogaster males kept individually are more aggressive and sexually active than males kept in a group. In the present study, we tested the locomotor activity of individual males and females previously reared either individually, or in a group. We found that keeping 20 young males for three days together led to a strong long-term (up to 5 days) reduction in their further locomotor activity as individuals. Rearing of young males in groups of other sizes (2, 5, 10, and 30) produced a smaller or no after-effect. At the same time, we have not found any difference in subsequent behavior of individual females previously kept either individually, or in a group. We suppose that in a group, flies learned to suppress their locomotor activity to prevent unpleasant contacts with other animals (operant learning). It seems that in males this learning is more efficient because of the higher level of aggression producing the stronger negative reinforcement.展开更多
Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indi...Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg;animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.展开更多
BACKGROUND Globally,complete neurological recovery of spinal cord injury(SCI)is still less than 1%,and 90%experience permanent disability.The key issue is that a pharmacological neuroprotective-neuroregenerative agent...BACKGROUND Globally,complete neurological recovery of spinal cord injury(SCI)is still less than 1%,and 90%experience permanent disability.The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found.The secretomes of stem cell are an emerging neurotrophic agent,but the effect of human neural stem cells(HNSCs)secretome on SCI is still unclear.AIM To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats.METHODS An experimental study was conducted with 45 Rattus norvegicus,divided into 15 normal,15 control(10 mL physiologic saline),and 15 treatment(30μL HNSCssecretome,intrathecal T10,three days post-traumatic).Locomotor function was evaluated weekly by blinded evaluators.Fifty-six days post-injury,specimens were collected,and spinal cord lesion,free radical oxidative stress(F2-Isoprostanes),nuclear factor-kappa B(NF-κB),matrix metallopeptidase 9(MMP9),tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor(VEGF),B cell lymphoma-2(Bcl-2),nestin,brain-derived neurotrophic factor(BDNF),glial cell line-derived neurotrophic factor(GDNF)were analyzed.The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling(PLS SEM).RESULTS HNSCs-secretome significantly improved locomotor recovery according to Basso,Beattie,Bresnahan(BBB)scores and increased neurogenesis(nestin,BDNF,and GDNF),neuroangiogenesis(VEGF),anti-apoptotic(Bcl-2),anti-inflammatory(IL-10 and TGF-β),but decreased proinflammatory(NF-κB,MMP9,TNF-α),F2-Isoprostanes,and spinal cord lesion size.The SCI regeneration mechanism is valid by analyzed outer model,inner model,and hypothesis testing in PLS SEM,started with pro-inflammation followed by anti-inflammation,anti-apoptotic,neuroangiogenesis,neurogenesis,and locomotor function.CONCLUSION HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.展开更多
基金Startup Fund for scientific research,Fujian Medical University,Grant/Award Number:2020QH1039Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2020Y9114 and 2020Y9119。
文摘The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.
基金supported by the National Natural Science Foundation of China,No.82272484(to XC).
文摘The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.
基金supported by Hong Kong Spinal Cord Injury Fund (HKSCIF),China (to HZ)。
文摘For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.
基金supported by the National Natural Science Foundation of China,Nos.82030071 (to JH),82272495 (to YC)Science and Technology Major Project of Changsha,No.kh2103008 (to JH)Graduate Students’ Independent Innovative Projects of Hunan Province,No.CX20230311 (to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
基金supported by a grant from The Institute for Rehabilitation and Research Foundation,No.MC018-112(to PW)John S.Dunn Foundation,No.18168(to PW)+2 种基金the National Natural Science foundation of China,Nos.81620108018(to SQF),81930070(to SQF),82072439(to GZN)Tianjin Key Research and Development Plan,Key Projects For Science and Technology Support of China,No.19YFZCSY00660(to SQF)the National Key R&D Program of China,No.2019YFA0112100(to SQF).
文摘Metformin,a first-line drug for type-2 diabetes,has been shown to improve locomotor recovery after spinal cord injury.However,there are studies reporting no beneficial effect.Recently,we found that high dose of metformin(200 mg/kg,intraperitoneal)and acute phase administration(immediately after injury)led to increased mortality and limited locomotor function recovery.Consequently,we used a lower dose(100 mg/kg,i.p.)metformin in mice,and compared the effect of immediate administration after spinal cord injury(acute phase)with that of administration at 3 days post-injury(subacute phase).Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale(BMS)scoring.Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site.Furthermore,metformin treatment at the subacute phase reduced neutrophil infiltration.These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin.These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection.This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch(approval No.1008041C)in 2010.
基金supported by grants from Innovative Team Project of Nanjing Normal University(Project No.0319PM0902)Priority Academic Program Development of Jiangsu Higher Education Institutions(CXLX11_0885)to Xiang JI
文摘Tail autotomy is a defense mechanism used by many lizards to evade predators, but it entails costs. We used the oriental leaf-toed gecko Hemidactylus bowringii as a model animal to evaluate locomotor costs of tail autotomy. We removed the tail about 5 mm from the tail base from each of the experimental geckos(adult males) initially having intact tails. Tailless experimental geckos and tailed control geckos were measured for overall speed and sprint speed in both vertical and horizontal directions. Overall speed and sprint speed did not differ between tailless and tailed geckos. The influence of locomotor direction on both overall speed and sprint speed was significant, with horizontal speed being greater than vertical speed. The interaction between tail condition and locomotor direction was not significant in overall speed, but was significant in sprint speed. Tailless geckos had faster vertical sprint speed than the tailed individuals. Of the 130 field-caught adults, 59 had previously lost their tails, with most(about 61%) of them shedding their tails near the tail base. Neither the proportion of geckos with tail autotomy nor the frequency distribution of locations of the tail break differed between the sexes. Our data show that tail loss of H. bowringii occurs frequently in nature. However, tail loss does not incur locomotor costs in this gecko.
基金partially supported by the MBRS-RISE Program(R25 GM061838)MBRS-SCORE(SO6-GM08224)+2 种基金COBRE(5P20-GM103642)SNRP(NS39405)RCMI(8G12MD007600)
文摘The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4- chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nudeotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.
文摘We studied the locomotor behaviour of white-headed langurs Trachypithecus leucocephalus and Francois' langurs T.francoisi to test two hypotheses: (1) these monkeys have evolved locomotor ability to support their activities on limestone hills, and (2) Francois' langurs have evolved more diverse locomotor skills than white-headed langurs. Data were collected from 1996 - 1998 and in 2005 in Fusui Nature Reserve, Guangxi, and showed that the two species had similar locomotor types, but Francois' langurs had more locomotor modes (26) than white-headed langurs (12). Quadrupedal walking and leaping were two major types, and white-headed langurs were more arboreal than Francois' langurs. We suggest that, while keeping their ancestral locomotor types, the two species have evolved new types allowing them to live on limestone cliffs. Compared to white-headed langurs, Francois' langurs have more diverse locomotor modes that probably have allowed them to live in more habitat types. As an evolutionary outcome, Francois' langurs have a larger distribution range .
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.
文摘Objective:To evaluate the neuroprotective effects of the organic components of scallop shells(scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5,10-imine(MK801).Methods:Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test,the Morris water maze test,and the open field test.Results:Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test.Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex.Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine.Scallop shell extract also suppressed the increase in locomotor activity induced by MK801.Conclusions:Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion.
基金funded by the National Natural Science Foundation of China (Grant Nos. 31601870 and 51435008)Natural Science Foundation of Jiangsu Province, China (Grant No. SBK20160800 to Zhouyi WANG)Jiangsu Provincial Key Laboratory of Bionic Functional Materials
文摘Animals have evolved a variety of behavior patterns to adapt to the environment. Motion-capture technology is utilized to quantify and characterize locomotor behaviors to reveal the mechanisms of animal motion. In the capture of flexible, small animals with complex locomotor behaviors, the markers interfere with each other easily, and the motion forms(bending, twisting) of the moving parts are obviously different;thus, it is a great challenge to realize accurate quantitative characterization of complex locomotor behaviors. The correlation between the marker properties, including the size and space length, and the precision of the system are revealed in this paper, and the effects of diverse marker shapes on the capturing accuracy of the captured objects in different motion forms were tested. Results showed that the precision of system is significantly improved when the ratio of the space length to the diameter of the markers is larger than four;for the capture of the spatial twisting motion of the flexible object, the hexagon markers had the lowest spatial lost-marker rate relative to the circle, triangle, and square. Customized markers were used to capture the locomotor behavior of the gecko-inspired robot(rigid connection) and the gecko(flexible connection). The results showed that this marking technology can achieve high accuracy of motion capture for geckos(the average deviation was approximately 0.32 mm, and the average deviation’s variation rate was approximately 0.96%). In this paper, the marking technology for the motion capture of flexible, small animals with complex motion is proposed;it can effectively improve the system precision as well as the capture accuracy, and realize the quantitative characterization of the complex motion of flexible, small objects. It provides a reliable technical means to deeply study the evolution of the motion function of small animals and advance systematic research of motion-capture technology.
文摘This study sought to elucidate the changes of nuclear factor kappa B (NF-KB) expression and locomotor function of hind limb after subdural injection of BMS-345541 was applied in rats with acute spinal cord injury. The results indicated that BMS-345541 treatment reduced the expression of NF-kB at 24 hours after injury, compared with normal saline-treated rats. This treatment also led to a significant improvement in locomotor functional recovery at 14 days after injury. Overall, the findings demonstrated that BMS-345541 significantly ameliorated spinal cord injury-induced hind limb dysfunction by inhibiting the expression of NF-kB after spinal cord injury.
基金the National Natural Science Foundation of China,No.30801222(to JZB).
文摘Oscillating field stimulation(OFS)is a potential method for treating spinal cord injury.Although it has been used in spinal cord injury(SCI)therapy in basic and clinical studies,its underlying mechanism and the correlation between its duration and nerve injury repair remain poorly understood.In this study,we established rat models of spinal cord contusion at T10 and then administered 12 weeks of OFS.The results revealed that effectively promotes the recovery of motor function required continuous OFS for more than 6 weeks.The underlying mechanism may be related to the effects of OFS on promoting axon regeneration,inhibiting astrocyte proliferation,and improving the linear arrangement of astrocytes.This study was approved by the Animal Experiments and Experimental Animal Welfare Committee of Capital Medical University(supplemental approval No.AEEI-2021-204)on July 26,2021.
基金supported by a grant from National Institute of Health(NIH)Grant No.NS040433
文摘Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival.Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression.Use of the m SOD1 G93 A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients,while investigating underlying disease-induced changes.In the present study,we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom,resembling the common gait abnormality foot drop,along with an accompanying forelimb compensatory mechanism in the m SOD1 G93 A mouse.Following these initial changes,m SOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait.As the disease progressed,these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared.We next applied these initial findings to investigate the inherent variability in B6 SJL m SOD1 G93 A survival.We identified four behavioral variables that,when combined in a cluster analysis,identified two subpopulations with different disease progression rates:a fast progression group and a slow progression group.This behavioral assessment paradigm,with its analytical approaches,provides a method for monitoring disease progression and detecting m SOD1 subgroups with different disease severities.This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression.Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.
文摘There are no reports on the effect of amphetamine on female WKY circadian activity pattern. The objective of this study is to investigate whether repeated daily exposure to the psychostimulant amphetamine alters the locomotor circadian rhythm activity patterns of female adult Wistar-Kyoto (WKY) rats. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12 h light/dark cycle in an open field cage. After 5 to 7 days of acclimation, 11 days of consecutive non-stop recordings began. On experimental day 1, all groups were given an injection of saline. On experimental days 2 to 7, the experimental group was injected with 0.6 mg/kg amphetamine and the control group with saline followed by a washout phase from experimental day 8 to 10, and amphetamine re-challenge or saline on experimental day 11 similar to experimental day 2. Locomotor movements were determined using a computerized animal activity monitoring system, and cosine statistical analysis was used to fit a24-hour curve to the activity pattern. The horizontal activity (HA), total distance (TD), number of stereotypy (NOS), and stereotypical movements (SM) were analyzed for alterations in the circadian rhythm activity patterns. The data demonstrated that chronic amphetamine administration alters the mesor parameter of the circadian rhythm activity patterns, indicating that chronic amphetamine treatment exerts long term effects on these rats.
文摘Previous social experience may affect subsequent behavior. It was shown by other authors that Drosophila melanogaster males kept individually are more aggressive and sexually active than males kept in a group. In the present study, we tested the locomotor activity of individual males and females previously reared either individually, or in a group. We found that keeping 20 young males for three days together led to a strong long-term (up to 5 days) reduction in their further locomotor activity as individuals. Rearing of young males in groups of other sizes (2, 5, 10, and 30) produced a smaller or no after-effect. At the same time, we have not found any difference in subsequent behavior of individual females previously kept either individually, or in a group. We suppose that in a group, flies learned to suppress their locomotor activity to prevent unpleasant contacts with other animals (operant learning). It seems that in males this learning is more efficient because of the higher level of aggression producing the stronger negative reinforcement.
文摘Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg;animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.
文摘BACKGROUND Globally,complete neurological recovery of spinal cord injury(SCI)is still less than 1%,and 90%experience permanent disability.The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found.The secretomes of stem cell are an emerging neurotrophic agent,but the effect of human neural stem cells(HNSCs)secretome on SCI is still unclear.AIM To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats.METHODS An experimental study was conducted with 45 Rattus norvegicus,divided into 15 normal,15 control(10 mL physiologic saline),and 15 treatment(30μL HNSCssecretome,intrathecal T10,three days post-traumatic).Locomotor function was evaluated weekly by blinded evaluators.Fifty-six days post-injury,specimens were collected,and spinal cord lesion,free radical oxidative stress(F2-Isoprostanes),nuclear factor-kappa B(NF-κB),matrix metallopeptidase 9(MMP9),tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor(VEGF),B cell lymphoma-2(Bcl-2),nestin,brain-derived neurotrophic factor(BDNF),glial cell line-derived neurotrophic factor(GDNF)were analyzed.The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling(PLS SEM).RESULTS HNSCs-secretome significantly improved locomotor recovery according to Basso,Beattie,Bresnahan(BBB)scores and increased neurogenesis(nestin,BDNF,and GDNF),neuroangiogenesis(VEGF),anti-apoptotic(Bcl-2),anti-inflammatory(IL-10 and TGF-β),but decreased proinflammatory(NF-κB,MMP9,TNF-α),F2-Isoprostanes,and spinal cord lesion size.The SCI regeneration mechanism is valid by analyzed outer model,inner model,and hypothesis testing in PLS SEM,started with pro-inflammation followed by anti-inflammation,anti-apoptotic,neuroangiogenesis,neurogenesis,and locomotor function.CONCLUSION HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.