查看更多>>摘要：Background:Hand,foot and mouth disease(HFMD)is a common infectious disease caused by viral infection by a variety of enteroviruses,with coxsackievirus A 10(CA10)having become more prevalent in recent years.Methods:In this study,models of CA10 infection were established in 7-day-old Institute of Cancer Research(ICR)mice by intraperitoneal injection to analyze the pathogenicity of the virus.RNA sequencing analysis was used to screen the differentially expressed genes(DEGs)after CA10 infection.Coxsackievirus A 16(CA16)and enterovirus 71(EV71)infections were also compared with CA10.Results:After CA10 virus infection,the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection.We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle.The RNA-sequencing analysis showed that the DEGs in blood,muscle,thymus and spleen showed heterogeneity after CA10 infection and the most up-regulated DEGs in muscle were enriched in immune-related pathways.Compared with CA16 and EV71 infection,CA10 may have an inhibitory effect on T helper(Th)cell differentiation and cell growth.Additionally,the common DEGs in the three viruses were most enriched in the immune system response,including the Toll-like receptor pathway and the nucleotide-binding and oligomerization domain(NOD)-like pathway.Conclusions:Our findings revealed a group of genes that coordinate in response to CA10 infection,which increases our understanding of the pathological mechanism of HFMD.
查看更多>>摘要：Background:Paraplegia after spinal cord ischemia is a devastating condition in the clinic.Here,we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury.Methods:A total of 47 male rabbits were involved in the present study.Transient spi-nal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures.To find the optimal conditions for devel-oping delayed paraplegia,hindlimb motor function after ischemia was evaluated be-tween experiments.Results:The onset and magnitude of ischemic injury varied with the ambient tem-perature maintained during the peri-ischemia period.More serious spinal cord injury occurred when ischemia was induced at higher temperatures.At 18℃,25-minute ischemia resulted in 74％of rabbits developing delayed paraplegia.At a temperature of 28℃ or higher,most of the animals developed acute paraplegia immediately.While at 13℃,rabbits usually regained normal motor function without paraplegia.Conclusion:This awake rabbit model is highly reproducible and will be helpful in fu-ture studies of delayed paraplegia after spinal cord ischemia.The ambient tempera-ture must be considered while using this model during investigation of therapeutic interventions.
查看更多>>摘要：Background:Blocking the RhoA/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2)signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke,cerebral ischemia,and suba-rachnoid hemorrhage.Nevertheless,it is not clear whether and how disrupting the RhoA/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier(BBB)after intracerebral hemorrhage(ICH).The present inves-tigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH.Methods:Scalp acupuncture(SA)therapy was performed on rats with ICH at the acu-puncture point"Baihui"-penetrating"Qubin,"and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK Ⅱ/MLC 2 signaling pathway.Post-assessments included neurological deficits,brain edema,Evans blue extravasation,Western blot,quantitative polymer-ase chain reaction,and transmission electron microscope imaging.Results:We found that ROCK Ⅱ acts as a promoter of the RhoA/ROCK Ⅱ/MLC 2 signaling pathway,and its expression increased at 6h after ICH,peaked at 3 days,and then decreased at 7days after ICH,but was still higher than the pre-intervention level.According to some experimental results,although 3 days is the peak,7 days is the best time point for acupuncture treatment.Starting from 6h after ICH,the neurovascular structure and endothelial cell morphology around the hematoma began to change.Based on the changes in the promoter ROCK Ⅱ,a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment.The results of this experiment showed that both SA at"Baihui"-penetrating"Qubin"and treatment with fasudil could improve the ex-pression of endothelial-related proteins by inhibiting the RhoA/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction,brain edema,and BBB per-meability in rats.Conclusion:This study found that these experimental data indicated that SA at"Baihui"-penetrating"Qubin"could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.
查看更多>>摘要：Background:Spinal cord injury presents a significant burden globally,with traumatic spinal cord injury being the predominant cause historically.However,nontraumatic spinal cord injury(NTSCI)is emerging as a significant contributor,particularly in devel-oped nations,yet it remains poorly understood due to underreporting and misclassifi-cation.NTSCI,spanning various etiologies such as bony growths,vascular conditions,infections,neoplastic conditions,and immune disorders,poses unique challenges in diagnosis and treatment,often resulting in lifelong morbidity.This study addresses the lack of suitable animal models for NTSCI research,especially in neonatal animals.Methods:Utilizing a solid spacer approach,we developed a compression NTSCI model applicable to both neonatal and adult Sprague-Dawley rats.Results:Through anatomical measurements and in vivo experiments,we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects.Conclusion:The versatility of this model lies in its adaptability to different ages of rats,offering a cost-effective and reproducible means to induce graded injuries.Moreover,behavioral assessments demonstrated observable hindlimb function,validating the model's utility for studying functional outcomes.Although challenges persist,par-ticularly in accounting for spinal column growth in neonatal animals,this model fills a crucial gap in pediatric NTSCI research.By providing a platform to investigate patho-physiological mechanisms and test potential treatments,it offers promising avenues for advancing our understanding and management of pediatric NTSCI.
查看更多>>摘要：Background:An increase in epidural pressure around the stenosis has been observed in patients with lumbar spinal stenosis(LSS)with positive signs of sedimentation or redundant nerve roots.Further analysis of the pressure conditions in the stenotic area would be of great interest.We hypothesized that it would be possible to determine the physiological parameters of the epidural pulse wave and its course in pathological stenosis as a basis for objective identification of LSS based on pressure using a new measuring method with continuous spatial and temporal resolution.Methods:We performed a single-case proof-of-principle in vivo animal trial and used a newly developed hybrid pressure-measurement probe with a fiber-tip Fabry-Pérot interferometer and several fiber Bragg gratings(FBG).Results:With reproducible precision,we determined the mean epidural pressure to be 7.5 mmHg and the peak-to-peak value to be 4-5 mmHg.When analyzing the pres-sure measured by an FBG array,both the heart and respiratory rates can be precisely determined.This study was the first to measure the pulse wave velocity of the cer-ebrospinal fluid pressure wave as 0.97 m/s using the newly developed pressure probe.A simulated LSS was detected in real time and located exactly.Conclusions:The developed fiber-optic pressure sensor probe enables a new objec-tive measurement of epidural pressure.We confirmed our hypothesis that physiologi-cal parameters of the epidural pulse wave can be determined and that it is possible to identify an LSS.
查看更多>>摘要：Streptozotocin(STZ)-induced type Ⅰ diabetes mellitus(DM)models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglyce-mia akin to human type Ⅰ diabetes.However,these models often suffer from poor induction rates and low survival post-STZ induction,especially in long-term experi-ments,necessitating insulin supplementation,which introduces additional variables to experiments.To address this,we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplemen-tation.Our method involves non-fasting,low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer,administered over 5 days.We observed hyperglycemia induction in 94.28％of mice within a week post-injection,with stable high blood glucose levels,stable body weight,and minimal mortality up to 21 weeks.Notably,omitting 10％sucrose in water and fasting did not affect hyperglycemia induction.Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers,but reduces animal stress and mortality,thus enhancing experimental outcomes and animal welfare.By opti-mizing the STZ-induced DM model in C57BL/6J mice,our study provides a valuable resource for researchers aiming to study diabetes and its complications while mini-mizing experimental variability and animal usage.
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