Establishment and evaluation of animal models of sepsis-associated encephalopathy

BACKGROUND:Sepsis-associated encephalopathy(SAE) is a critical disease caused by sepsis.In addition to high mortality,SAE can also adversely aff ect life quality and lead to significant socioeconomic costs.This review aims to explore the development of evaluation animal models of SAE,giving insight into the direction of future research in terms of its pathophysiology and therapy.METHODS:We performed a literature search from January 1,2000,to December 31,2022,in MEDLINE,PubMed,EMBASE,and Web of Science using related keywords.Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies.RESULTS:The animal models for sepsis are commonly induced through cecal ligation and puncture(CLP) or lipopolysaccharide(LPS) injection.SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase,or through Morris water maze(MWM),openfield test,fear condition(FC) test,inhibitory avoidance,and other tests during the late phase.CONCLUSION:CLP and LPS injection are the most common methods for establishing SAE animal models.Nervous reflexs cores,MWM,FC test,and inhibitory avoidance are widely used in SAE model analysis.Future research should focus on establishing a standardized system for SAE development and analysis.

Risk factors for sepsis-associated encephalopathy

Sepsis-associated encephalopathy （SAE） is a diffuse and acute cerebral dysfunction caused by sepsis. Many sepsis patients exhibit acute deterioration in mental status during the early stage of disease, and central nervous system dysfunction has been shown to increase patient mortality. The present study selected 284 sepsis patients who were admitted to the Intensive Care Unit of Beijing Friendship Hospital, Capital Medical University, from January to December 2009. The patients were assigned to SAE and non-SAE patient groups according to SAE occurrence. SAE incidence was 37.68%, and mortality was significantly greater in SAE patients compared with non-SAE patients （41.12% vs. 17.51%, P 〈 0.01）. Univariate analysis and multivariate logistic regression analysis indicated lower arterial partial pressure of oxygen and greater alanine aminotransferase and Acute Physiology and Chronic Health Evaluation II scores in the SAE group compared with the non-SAE group. Arterial partial pressure of oxygen, alanine aminotransferase, and Acute Physiology and Chronic Health Evaluation II scores were determined to be potential risk factors for SAE.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial

BACKGROUND:Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy(SAE)is a major complication.Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions.Our study aimed to explore the potential protective function of rosuvastatin against SAE.METHODS:Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the“Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome”study(SAILS trial,ClinicalTrials.gov number:NCT00979121).Patients were divided into rosuvastatin and placebo groups.This is a secondary analysis of the SAILS dataset.Baseline characteristics,therapy outcomes,and adverse drug events were compared between groups.RESULTS:A total of 86 patients were eligible for our study.Of these patients,51 were treated with rosuvastatin.There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group(32.1%vs.57.1%,P=0.028).However,creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group(233[22-689]U/L vs.79[12-206]U/L,P=0.034).CONCLUSION:Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Effects of Hydrogen Sulfide on a Rat Model of Sepsis-associated Encephalopathy

To investigate the interaction and involvement of sodium hydrosulfide （NaHS）, a H2S donor, on hippocampus of rats suffering from sepsis-associated encephalopathy, rats were subjected to cecal ligation and puncture （CLP）-induced sepsis. Adult male Sprague-Dawley rats were randomly divided into four groups： Sham group, CLP group, CLP＋NaHS group and CLP＋aminooxyacetic acid （AOAA, an inhibitor of H2S formation） group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H2S synthesis and the expression of cystathionine-β-synthetase （CBS）, a major enzyme involved in the H2S synthesis in hippocampus. CBS expression was detected by reverse transcription polymerase chain reaction （RT-PCR）. The concentrations of inflammatory cytokines （TNF-α, IL-1β） were determined in hippocampus by using enzyme-linked immunosorbent assay （ELISA）. Neuronal damage was studied by histological examination of hippocampus. In CLP group, H2S synthesis was significantly increased in hippocampus compared with sham group and it peaked 3 h after CLP （P〈0.05）. Sepsis also resulted in a significantly upregulated CBS mRNA in hippocampus. The levels of TNF-α and IL-1β in the hippocampus were substantially elevated at each time point of measurement （P〈0.05）, and they also reached a peak value at about 3 h. Administration of NaHS significantly aggravated sepsis-associated hippocampus inflammation, as evidenced by TNF-α and IL-1β activity and histological changes in hippocampus. In septic rats pretreated with AOAA, sepsis-associated hippocampus inflammation was reduced. It is concluded that the rats subjected to sepsis may suffer from brain injury and elevated pro-inflammatory cytokines are responsible for the process. Furthermore, administration of H2S can increase injurious effects and treatment with AOAA can protect the brain from injury.

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients： 2008-2011

Background Encephalopathy is a common complication of sepsis, and its onset can occur at any stage of sepsis and implies worse prognosis. However, the incidence, epidemiology, and pathogenesis of sepsis-associated encephalopathy remain controversial. The purpose of this study was to investigate the epidemiological features and risk factors for sepsis-associated encephalopathy.

Diagnostic and Predictive Levels of Calcium-binding Protein A8 and Tumor Necrosis Factor Receptor-associated Factor 6 in Sepsis-associated Encephalopathy： A Prospective Observational Study

Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% specificity and 68.40% sensitivity, and the area under the curve was 0.77. Compared with TRAF6, the specificity of serum S 100A8 in diagnosing SAE and predicting mortality was higher, although the sensitivity was low. In contrast, the TRAF6 had higher sensitivity for diagnosis. Conclusions： Peripheral blood levels of S 100A8 and TRAF6 in SAE patients were elevated and might be related to the severity of SAE and predict the outcome of SAE. The efficacy and specificity of S 100A8 for SAE diagnosis were superior, despite its weak sensitivity. S100A8 might be a better biomarker for diagnosis of SAE and predicting prognosis.

Basic research and clinical progress of sepsis-associated encephalopathy

Sepsis-associated encephalopathy(SAE),a major cerebral complication of sepsis,occurs in 70%of patients admitted to the intensive care unit(ICU).This condition can cause serious impairment of consciousness and is associated with a high mortality rate.Thus far,several experimental screenings and radiological techniques(e.g.,electroencephalography)have been used for the non-invasive assessment of the structure and function of the brain in patients with SAE.Nevertheless,the pathogenesis of SAE is complicated and remains unclear.In the present article,we reviewed the currently available literature on the epidemiology,clinical manifestations,pathology,diagnosis,and management of SAE.However,currently,there is no ideal pharmacological treatment for SAE.Treatment targeting mitochondrial dysfunction may be useful in the management of SAE.

Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury

BACKGROUND:To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor(MANF) in regulating sepsis-associated acute kidney injury(S-AKI).METHODS:A total of 96 mice were randomly divided into the control group,control+MANF group,S-AKI group,and S-AKI+MANF group.The S-AKI model was established by injecting lipopolysaccharide(LPS) at 10 mg/kg intraperitoneally.MANF(200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups.An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups.Serum and kidney tissue samples were obtained for biochemical analysis.Western blotting was used to detect the protein expression of MANF in the kidney,and enzyme-linked immunosorbent assay(ELISA) was used to determine expression of MANF in the serum,pro-inflammatory cytokines(tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]).Serum creatinine(SCr),and blood urea nitrogen(BUN)were examined using an automatic biochemical analyzer.In addition,the kidney tissue was observed for pathological changes by hematoxylin-eosin staining.The comparison between two groups was performed by unpaired Student’s t-test,and statistics among multiple groups were carried out using Tukey’s post hoc test following one-way analysis of variance(ANOVA).A P-value <0.05 was considered statistically significant.RESULTS:At the early stage of S-AKI,MANF in the kidney tissue was up-regulated,but with the development of the disease,it was down-regulated.Renal function was worsened in the S-AKI group,and TNF-α and IL-6 were elevated.The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney.The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group.CONCLUSION:MANF treatment may significantly alleviate renal injury,reduce the inflammatory response,and alleviate or reverse kidney tissue damage.MANF may have a protective effect on S-AKI,suggesting a potential treatment for S-AKI.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.

Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.

Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

Magnetic resonance imaging scanning susceptibility weighted imaging sequences in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE).AIM To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.METHODS The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August,2021 to December,2023.The results of clinical judgment were compared with the results of computed tomography(CT)and MRI examinations.RESULTS The degree of cerebral edema(more than moderate),the number of damaged brain regions(>2),the number of cerebral hemorrhages(>2),and the percentage of small venous dilatation detected were higher in MRI than in CT examination,and the differences were statistically significant(P<0.05).The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination(P<0.01).Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis,and the difference was statistically significant(P<0.05).The difference in the specificity of the two modes of diagnosis was not significant(P>0.05).CONCLUSION The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Subdural effusion associated with COVID-19 encephalopathy: A case report

BACKGROUND The precise mechanism by which severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)impacts the central nervous system remains unclear,with manifestations spanning from mild symptoms(e.g.,olfactory and gustatory deficits,hallucinations,and headache)to severe complications(e.g.,stroke,seizures,encephalitis,and neurally demyelinating lesions).The occurrence of single-pass subdural effusion,as described below,is extremely rare.CASE SUMMARY A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms.Through comprehensive imaging and diagnostic assessments,he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal,temporal,and parietal regions.In addition,an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process;consequently,an idiopathic subdural effusion developed.Remarkably,the subdural effusion underwent absorption within 6 d,with no recurrence observed during the 3-month follow-up.CONCLUSION Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.

Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

Progress in pathogenesis and treatment of type A hepatic encephalopathy in acute liver failure:a comprehensive review

Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.