Cholesterol crystal embolism leading to perforation of the gallbladder

BACKGROUND: Cholesterol crystal embolism (CCE) from atherosclerotic arterial disease leading to perforation of the gallbladder is rare. We describe our experience of managing a patient with perforation of gallbladder caused by CCE. METHODS: A 64-year-old man was admitted to this hospital because of acute abdominal pain with clinical features suggestive of peritonitis. He was known to suffer from atherosclerotic peripheral arterial disease and had undergone aortobifemoral bypass 17 years ago. A CT scan showed a collection of peri-hepatic fluid. The gallbladder was normal in appearance but contained multiple calculi. At laparotomy, free bile was observed in the peritoneal cavity, leaking from a pin-hole size peroration of the fundus of the gallbladder. Hence cholecystectomy was performed. RESULTS: The patient made an uneventful recovery. Histological study of the gallbladder showed chronic cholecystitis and obliteration of the lumen of the mural arteries with cholesterol crystals within, indicating CCE. CONCLUSIONS: Although perforation of the gallbladder following CCE of its mural arteries is rare, the diagnosis should be considered in patients with abdominal pain and known atherosclerotic arterial disease. Management should include an early recognition of this condition, prompt institution of treatment, prevention of further insults by discontinuing or avoiding predisposing factors, and modification of cardiovascular risk factors.

Idiopathic cholesterol crystal embolism with atheroembolic renal disease and blue toes syndrome:A case report

BACKGROUND Cholesterol crystal embolization(CCE)is a multisystemic and fatal disease with multiple clinical manifestations;however,there are few cases of idiopathic CCE.Here we report a patient with idiopathic CCE accompanied by atheroembolic renal disease and blue toes who had a relatively good prognosis in the short-term due to early treatment with corticosteroids and statins.CASE SUMMARY A 76-year-old man complained of coldness,numbness and purple color change in his left foot for 7 d.He had a feeling of fatigue,constipation,foamy urine,poor appetite and sleep.He had a lacunar infarction for 5 years and hypertension for 9 mo.Laboratory results showed elevated eosinophils,cholesterol,uric acid,serum creatinine,urea and 24 h urine analysis revealed proteinuria.A renal biopsy revealed atheroembolic renal disease.Taken together,these findings strongly supported the diagnosis of idiopathic CCE and atheroembolic renal disease.CONCLUSION Atheroembolic renal disease and blue toes syndrome can be caused by idiopathic CCE,and early treatment with corticosteroids is effective but requires further investigation.

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

Cronkhite-Canada syndrome complicated with pulmonary embolism:A case report

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare disease,that causes gastrointestinal polyps,ectodermal abnormalities,and gastrointestinal symptoms.CCS is prone to thromboembolism,but clinical workers have not yet established a clinical consciousness of preventing thromboembolism.The present case illustrates pulmonary embolism(PE)complicated by CCS.CASE SUMMARY A 46-year-old male patient presented with mucus,purulent,and bloody stool.Ectodermal changes included skin pigmentation,alopecia,and nail dystrophy.Colonoscopy revealed the presence of multiple polyps.After a comprehensive evaluation,the patient was diagnosed with CCS.During the disease,he was also diagnosed with pulmonary embolism,Riehl's melanosis,and intestinal flora imbalance.After symptomatic treatment with omeprazole,mesalazine,rivaroxaban,nutritional support,and regulation of intestinal flora,the patient’s symptoms were significantly relieved.CONCLUSION CCS complicated with PE was reported for the first time in China in this study.Despite the fact that CCS is extremely rare,patients with CCS should be classified as a high-risk venous thromboembolism(VTE)population,and emphasis should be placed on venous thromboembolism risk assessment and stratification,deep venous thromboembolism screening,prevention of VTE,and careful long-term follow-up.

Pulmonary embolism secondary to acute anterior ST-elevation myocardial infarction:a case report

Thrombophilia denotes a condition,whether acquired or hereditary,characterized by increased susceptibility to hypercoagulation.[1]This condition was first described in 1965,coinciding with the discovery of an inherited predisposition to venous thromboembolism(VTE)in patients deficient in antithrombin III.[2]While arterial and venous thromboses are common in hospitalized patients,acute myocardial infarction(AMI)and pulmonary embolism(PE)stand out as lifethreateningconditions.However,theoccurrenceof AMI complicated by PE is exceedingly rare,especially when considering cases where paradoxical embolism originating from a patent foramen ovale is absent.This report presents a case of AMI complicated with PE.A comprehensive understanding of the pathophysiology of this rare yet critical condition is important for ensuring prompt diagnosis and treatment.

Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

Cholesterol and Sericin as First Aid for Damaged Cells

Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.

Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Inhibitory effect of procyanidin B2 and tannin acid on cholesterol esterase and their synergistic effect with orlistat

This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.

Research progress on the clinical diagnosis and treatment of COPD with pulmonary embolism

Chronic obstructive pulmonary disease(COPD)is one of the most common and important diseases leading to the death of elderly patients in the world at present.It is characterized by continuous airflow restriction and irreversible chronic airway obstruction,which can easily lead to a variety of complications and accompanying symptoms,greatly affecting the quality of life of individuals and increasing the economic burden of families and society.Pulmonary embolism(PE)is one of the complications of COPD,which can lead to pulmonary blood circulation and respiratory failure,with a high risk of death.However,because its clinical symptoms overlap with the symptoms of acute exacerbation of COPD and lack of specific clinical manifestations and laboratory tests,it is easy to be misdiagnosed and ignored,thus delaying the treatment of patients and affecting the prognosis.This article will elaborate on the clinical diagnosis and treatment of chronic obstructive pulmonary disease combined with pulmonary embolism,providing certain value for early identification of COPD combined with PE patients and the severity of the condition.

Associations between remnant cholesterol levels and mortality in patients with diabetes

BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.

Veno-arterial extracorporeal membrane oxygenation for the treatment of obstructive shock caused by venous air embolism:A case report

BACKGROUND Venous air embolism(VAE)is a potentially lethal condition,with a reported incidence rate of about 0.13%,and the true incidence may be higher since many VAE are asymptomatic.The current treatments for VAE include Durant's maneuver,aspiration and removal of air through venous catheters,and hyperbaric oxygen therapy.For critically ill patients,use of cardiotonic drugs and chest compressions remain useful strategies.The wider availability of extracorporeal membrane oxygenation(ECMO)has brought a new option for VAE patients.CASE SUMMARY A 53-year-old female patient with VAE presented to the emergency clinic due to abdominal pain with fever for 1 d and unconsciousness for 2 h.One day ago,the patient suffered from abdominal pain,fever,and diarrhea.She suddenly became unconscious after going to the toilet during the intravenous infusion of ciprofloxacin 2 h ago,accompanied by nausea and vomiting,during which a small amount of gastric contents were discharged.She was immediately sent to a local hospital,where cranial and chest computed tomography showed bilateral pneumonia as well as accumulated air visible in the right ventricle and pulmonary artery.The condition deteriorated despite endotracheal intubation,rehydration,and other treatments,and the patient was then transferred to our hospital.Veno-arterial ECMO was applied in our hospital,and the patient's condition gradually improved.The patient was successfully weaned from ECMO and extubated after two days.CONCLUSION ECMO may be an important treatment for patients with VAE in critical condition.

Multiple paradoxical embolisms caused by central venous catheter thrombus passing through a patent foramen ovale: A case report

BACKGROUND To date,this is the first case of a paradoxical embolism(PDE)that concurrently manifested in the coronary and lower limb arteries and was secondary to a central venous catheter(CVC)thrombus via a patent foramen ovale(PFO).CASE SUMMARY Here,we report a case of simultaneous coronary and lower limb artery embolism in a PFO patient carrier of a CVC.The patient presented to the hospital with acute chest pain and lower limb fatigue.Doppler ultrasound showed a large thrombus in the right internal jugular vein,precisely at the tip of the CVC.Transthoracic and transesophageal echocardiography confirmed the existence of a PFO,with inducible right-to-left shunting by the Valsalva maneuver.The patient was administered an extended course of anticoagulation therapy,and then the CVC was successfully removed.Percutaneous PFO closure was not undertaken.There was no recurrence during follow-up.CONCLUSION Thus,CVC-associated thrombosis is a potential source for multiple PDE in PFO patients.

Left ventricular thrombosis caused cerebral embolism during venoarterial extracorporeal membrane oxygenation support: A case report

BACKGROUND Venoarterial(VA)extracorporeal membrane oxygenation(ECMO),an effective short-term circulatory support method for refractory cardiogenic shock,is widely applied.However,retrospective analyses have shown that VA-ECMO-assisted cases were associated with a relatively high mortality rate of approximately 60%.Embolization in important organs caused by complications of left ventricular thrombosis(LVT)during VA-ECMO is also an important reason.Although the incidence of LVT during VA-ECMO is not high,the consequences of embolization are disastrous.CASE SUMMARY A 37-year-old female patient was admitted to hospital because of fever for 4 d and palpitations for 3 d.After excluding the diagnosis of coronary heart disease,we established a diagnosis of“clinically explosive myocarditis”.The patient still had unstable hemodynamics after drug treatment supported by VA-ECMO,with heparin for anticoagulation.On day 4 of ECMO support,a left ventricular thro-mbus attached to the papillary muscle root of the mitral valve was found by transthoracic echocardiography.Left ventricular decompression was performed and ECMO was successfully removed,but the patient eventually died of multiple cerebral embolism.CONCLUSION LVT with high mobility during VA-ECMO may cause embolism in important organs.Therefore,a"wait and see"strategy should be avoided.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Causal associations between intermediate very-low-density lipoprotein cholesterol-to-total lipids ratio and peptic ulcer:A bidirectional Mendelian randomization study

BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

The Value of MLPR,NLR,and RDW in the Assessment of Combined Pulmonary Embolism in Elderly Patients with AECOPD

Objective:To investigate the diagnostic value of the monocyte-to-large-platelet ratio(MLPR),neutrophil-to-lymphocyte ratio(NLR),and red blood cell distribution width(RDW)for pulmonary embolism(PE)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 60 elderly AECOPD patients were enrolled and divided into embolus group(12 cases)and thrombus group(48 cases)according to whether they were combined with pulmonary embolism and the MLPR,NLR,and RDW values of the two groups were determined respectively.Results:The patients in the two groups had different degrees of vascular structural and functional abnormalities,and the MLPR,NLR,and RDW in the embolus group were significantly higher than those in the thrombus group(P<0.05);while the differences in NLR and RDW between the two groups were not significant.Conclusion:MLPR,NLR,and RDW can provide an objective basis for assessing PE in elderly AECOPD patients.

Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.