Intracerebral hemorrhage in a child with renal artery stenosis and COVID-19

@#Pediatric intracerebral hemorrhage is a rare condition among children. We discuss the case of a 7-year-old Filipino male with generalized tonic seizures and diagnosed to have both SARS-CoV-2 infection and hypertension secondary to renal arterial stenosis. The occurrence of intracerebral hemorrhage in children, though commonly caused by arteriovenous malformations, may be secondary to an acute hypertensive episode. In this case, the presence of COVID-19 in the patient may have been contributory to the development of spontaneous intracerebral hemorrhage due to its direct endothelial effects, as well as its dysregulatory action on the renin-angiotensin-aldosterone system.

Effects of dexmedetomidine on activation of mast cells around hematoma and neurological impairment in mouse intracerebral hemorrhage / 重庆医学

Objective To explore the effect of dexmedetomidine on the neurological function and mast cells activation in the mouse with intracerebral hemorrhage(ICH).Methods The mouse was intraperitoneal-ly injected with dexmedetomidine at 30 min before intracerebral hemorrhage.After the preparation of intrace-rebral hemorrhage model,the neurological function,brain water content,number of mast cells around hemato-ma and expression levels of tryptase,IL-1β,TNF-α were detected.Results Compared with the control group,the neurological function score in the intracerebral hemorrhage group was significantly elevated(P＜0.05),the brain water content was significantly increased(P＜0.05),the mast cells number was significantly in-creased(P＜0.05),and the tryptase,IL-1β and TNF-α expression levels were sinificantly increased(P＜0.05);while the neurological function score in the dexmedetomidine group was significantly decreased(P＜0.05),the brain water content was significantly decreased(P＜0.05),the number of mast cells was signifi-cantly reduced and the tryptase,IL-1β and TNF-α expression levels were significantly decreased(P＜0.05).Conclusion Dexmedetomidine could inhibit the activation of mast cells around hematoma and reduce the dam-age of neurological function after mouse intracerebral hemorrhage.

Effects of gene silencing Cyclooxygenase-2 cooperated with hyperbaric oxygen on neurological repair and apoptosis, autophagy in cerebral hemorrhage rats / 中华急诊医学杂志

Objective:To investigate the effects of gene silencing inducible cyclooxygenase-2 (COX-2) combined with hyperbaric oxygen (HBO) on neuronal cell edema, apoptosis, autophagy and neural functional recovery in rats with intracerebral hemorrhage.Methods:SPF-grade adult male SD rats ( n=96) were used to establish a cerebral hemorrhage model through stereotactic injection of thrombin VII into the caudate nucleus. They were randomized (random number) into 4 groups ( n=24/group): control group, hyperbaric oxygen (HBO) group, COX-2 RNAi group and combined group (COX-2 RNAi+HBO). The siRNA plasmid targeting silencing COX-2 gene expression was constructed. After group treatment, the four rats were randomly selected from each group for testing in each category. Postoperative day 1, 7, and 14 were assessed using the modified neurological severity score (mNSS) for evaluating neurofunctional deficits. On the 7th day, the water content of the brain tissue was measured using the dry/wet weight method. The blood-brain barrier permeability was assessed using the Evans method. Annexin V and TUNEL assays were employed to assess the apoptotic rate of neural cells. The mRNA expression level of COX-2 in brain tissue was determined using the RT-PCR method. The protein expression levels of Beclin-1, COX-2, aquaporin 4 (AQP-4), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloprotein-2/9 (MMP-2/9) were detected by Western blot (WB). SPSS software was used for data analysis. One-way ANOVA was used for inter group comparisons and LSD- t test was used for further pairwise comparison. Results:The SD rat intracerebral hemorrhage model and plasmid construction were successfully achieved. The mNSS scores were significantly decreased in COX-2 RNAi, HBO and combined groups compared with control group on the 7th day and 14th day (all P<0.01), especially in combined group ( P<0.01). The contents of Evans blue and the water content of brain tissue of all treatment groups were significantly lower than those in control group (all P<0.05), especially in combined group ( P<0.01). The apoptotic rate of neural cells decreased in all treatment groups compared with the control group (all P<0.05), and the combined group decreased the most ( P<0.01). The mRNA expression levels of COX-2 were significantly decreased in all treatment groups compared with the control group (all P<0.01), and combined group silenced COX-2 expression most obviously ( P<0.05). The results of WB showed that the protein expression levels of Beclin-1, COX-2, AQP-4, Caspase-3, HIF-1α, MMP-2/9 were significantly lower than control group (all P<0.05), while the expression of Bcl-2 was increased in all treatment groups (all P<0.01). Among them, the combined group exhibited the most pronounced trend ( P<0.01). Conclusions:Gene silencing of COX-2 in combination with hyperbaric oxygen therapy can effectively restore neurological function in rats with cerebral hemorrhage. The mechanism may be associated with reduced blood-brain barrier permeability, alleviated brain edema, and inhibition of neuronal apoptosis and autophagy.

Silencing of activating transcription factor 4 inhibits neuronal necroptosis after intracerebral hemorrhage in vitro / 中国组织工程研究

BACKGROUND:Neuronal necroptosis induced by intracerebral hemorrhage is an important cause of secondary brain injury.Activating transcription factor 4(ATF4)is a member of the transcription activator family,which plays an important role in secondary brain injury after intracerebral hemorrhage.However,the mechanism of ATF4 in neuronal necroptosis after intracerebral hemorrhage remains unclear. OBJECTIVE:To explore the effect of ATF4 silencing(ATF4 small interfering RNA,ATF4 siRNA)on neuronal necroptosis after intracerebral hemorrhage. METHODS:The HT-22 mouse hippocampal neuron cell line and the BV-2 mouse microglial cell line were co-cultured,and hemin was used to mimic an in vitro model of intracerebral hemorrhage.A gradient concentration of hemin was used to treat cells and was set in the interval of 0-100 μmol/L,and the cell viability was evaluated by MTT assay after 24 hours of administration of hemin.The cells were divided into four groups:the blank control group without any intervention;the control group was treated with hemin(50 μmol/L),and the other two groups were treated with negative control small interfering RNA(NC siRNA)and ATF4 small interfering RNA(ATF4 siRNA)48 hours before administration of hemin.After the cells were treated with hemin(50 μmol/L)for 24 hours,PI/Hoechst staining was used to detect neuronal necroptosis.Western blot assay was used to detect the protein expression of ATF4,receptor-interacting protein 3(RIP3),and mixed lineage kinase domain-like protein(MLKL),and double immunofluorescent staining was located in neurons to observe the level of neuronal necroptosis and the regulatory effect of ATF4 on it. RESULTS AND CONCLUSION:(1)50 μmol/L of hemin could induce neuronal necroptosis to a greater extent.(2)The number of PI+/Hoechst+ cells in the control group and NC siRNA group was higher than that in the blank control group(P<0.000 1).The number of PI+/Hoechst+ cells in the ATF4 siRNA group was lower than that in the control group(P<0.000 1).(3)Compared with the control group,the ATF4 siRNA group not only inhibited the expression of ATF4 protein(P<0.001),but also inhibited the expression of RIP3 and MLKL protein(P<0.001).(4)Through double immunofluorescent staining,compared with the control group,the protein expression of RIP3 and MLKL was significantly reduced in the ATF4 siRNA group(P<0.000 1).(5)The results show that the silencing of the ATF4 gene can directly or indirectly inhibit the expression of genes related to neuronal necroptosis after intracerebral hemorrhage,and play a vital role in alleviating secondary brain injury.

Sequencing,verification and functional analysis of differentially expressed genes in brain tissue of a rat model with acute intracerebral hemorrhage / 中国组织工程研究

BACKGROUND:There are differentially expressed genes in acute intracerebral hemorrhage,which are related to the occurrence and development of intracerebral hemorrhage. OBJECTIVE:To screen differentially expressed genes and key genes in brain tissue of a rat model with acute intracerebral hemorrhage,to validate them through qPCR,and to analyze the relationships between key genes and the neurological function and brain tissue water content after intracerebral hemorrhage. METHODS:Seventy-eight Sprague-Dawley rats were randomly divided into two groups:in intracerebral hemorrhage group,a rat model of acute intracerebral hemorrhage was made using collagenase injection at the right caudate nucleus;and in sham-operated group,rats were injected with equal amount of saline at the same site.RNA was extracted from rat brain tissues of both groups using the TRIzol method and transcriptome sequencing technology was used to identify differentially expressed genes in brain tissues of acute intracerebral hemorrhage,which were then verified by qPCR and analyzed for the relationships between the genes and neurological function and brain tissue water content after intracerebral hemorrhage.And the key genes were analyzed by GO and KEGG functional enrichment analysis in combination with bioinformatics. RESULTS AND CONCLUSION:Ten key genes were identified,including CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20.The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E in the intracerebral hemorrhage group were lower than those in the sham-operated group(P＜0.05).The contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 in the intracerebral hemorrhage group were higher than those in the sham-operated group(P＜0.05).The contents of GDA,KCNQ5,ERICH3,SCN3B,and CACNA1E were positively correlated with brain tissue water content and neurologic deficit score(P＜0.05),while the contents of CXCL8,SERPINE1,TFPI2,CXCR4 and CCL20 were negatively correlated with brain tissue water content and neurologic deficit score(P＜0.05).GO analysis indicated that differentially expressed genes were mainly enriched in two biological processes(leukocyte chemotaxis and chemokine-mediated signaling pathways),two cell components(cation channel complexes and ion channel complexes),and two molecular functions(gated channel activity and ion channel activity).KEGG analysis indicated that differentially expressed genes were concentrated in tumor necrosis factor signaling pathway,glutamatergic synapses and GABAergic synapses.To conclude,the differentially expressed genes in intracerebral hemorrhage include CXCL8,SERPINE1,TFPI2,CXCR4,GDA,KCNQ5,ERICH3,SCN3B,CACNA1E,and CCL20,and these genes are related to brain tissue water content and neurological function after intracerebral hemorrhage.These genes are mainly enriched in cell components,binding functions,cellular protrusions,and other related biological functions.

Guidelines for the Selection of Animal Models and Preclinical Drug Trials for Spontaneous Intracerebral Hemorrhage (2024 Edition) / 实验动物与比较医学

Spontaneous intracerebral hemorrhage (sICH), the most prevalent and lethal subtype of stroke, is characterized by spontaneous hemorrhage in the brain parenchyma. Presently, there are no effective methods for preventing and treating sICH. The existing sICH animal models can be broadly categorized into three classes: (1) induced intracerebral hemorrhage models, including autologous blood injection model, collagenase injection model, microballoon inflation model, and hyperglycemia-induced sICH hematoma expansion model; (2) spontaneous hypertensive intracerebral hemorrhage models mainly include stroke-prone spontaneously hypertensive rats (SHRsp) and stroke-prone renovascular hypertensive rats (RHRsp); (3) gene-modified models encompassing transgentic hypertensive intracerebral hemorrhage, transgentic cerebral amyloid angiopathy, arteriovenous malformation-related, cerebral cavernous malformation-related and collagen-related genetically modified animal models for sICH. These models contribute not only to unraveling the pathogenesis of sICH and exploring preventive or therapeutic interventions, but also serve as invaluable tools for conducting preclinical drug trials to advance novel treatments. This guide comprehensively reviews sICH pathogenesis, delineates the superiority and inferiority of different species of modeling animals, explains the modeling principles and techniques for various sICH animal models, elucidates the technical details of animal model production, summarizes the pathophysiological mechanism simulated by the models and their clinical relevance, outlines the neurobehavioral evaluation methodologies for sICH animal models, compares the advantages and disadvantages of various models, and suggests their applicable research areas. Additionally, it underscores critical considerations in the design of preclinical drug trials for sICH.

Correlation between CT Blend Sign and Poor Outcomes after Craniotomy in Patients With Intracerebral Hemorrhage / 医学研究杂志

Objective To explore the effect of head CT blend signs on short-term outcomes in patients with spontaneous supraten-torial intracerebral hemorrhage(ICH)after craniotomy.Methods A total of 435 patients with spontaneous supratentorial ICH who un-derwent craniotomy in the Department of Neurosurgery,Jinyang Hospital Affiliated to Guizhou Medical University from January 2019 to December 2022 were enrolled retrospectively.The patients were divided into the blend sign group(n=105)and control group(n=330)based on the CT features at admission.The general clinical data,imaging data,surgical data,complications and prognosis were collected and compared between the two groups.The outcome was assessed by the mRS(modified Rankin scale)at discharge.Multivariate Logistic regression model was used to analyze the independent correlation between CT blend sign and poor outcomes.Results During the follow-up period,there was no significant differences in the proportion of patients with poor outcomes between the two groups.The poor outcomes after craniotomy was independently correlated with age,smoking history,diabetes history and Glasgow coma scale(GCS)at admission,but not with blend signs.Conclusion Head CT blend signs on admission is not associated with the poor outcomes in patients with sponta-neous supratentorial ICH after craniotomy.

Protective effect and mechanism of TLR4/NF-κB pathway regulated by miR-146a in intracerebral hemorrhage model rats / 中国免疫学杂志

Objective:To explore role of miR-146a in regulating TLR4/NF-κB pathway on inflammatory injury and neuropro-tection in intracerebral hemorrhage model rats and its possible mechanism.Methods:A total of 40 rats were selected and randomly divided into sham,model,over-expressing miR-146a adenovirus and negative virus injection groups,with 10 rats in each group.Garcia score was used for neurological function;HE staining was used to observe changes of brain tissues.ELISA was used to detect inflammatory factors levels.TLR4,NF-κB protein and gene expressions in brain tissues were detected by Western blot and RT-PCR.Results:Compared with model group,neural function score of overexpressed miR-146a adenovirus injection group was increased(P<0.05).Model group had abnormal cell morphology,edema and inflammation.Cell morphology,edema and inflammation were alleviated in overexpressed miR-146a adenovirus injection group.Inflammatory factors levels in model group were higher than sham group(P<0.05).Inflammatory factors levels in overexpressed miR-146a adenovirus injection group were lower than model group(P<0.05).TLR4,NF-κB protein and mRNA expressions in model group were increased than sham group(P<0.05).TLR4,NF-κB protein and mRNA expressions in overexpressed miR-146a adenovirus injection group were decreased than model group(P<0.05).Conclusion:miR-146a can improve neural function and reduce inflammatory injury in rats with intracerebral hemorrhage,possibly by inhibiting activation of TLR4/NF-κB signaling pathway and reducing inflammatory factors levels of brain tissues.

Descripción de los factores contribuyentes a las muertes secundarias a trastornos hipertensivos asociados al embarazo en Antioquia, Colombia (2012-2020) / Description of the contributing factors to deaths secondary to hypertensive disorders associated with pregnancy in Antioquia, Colombia (2012-2020)

Resumen OBJETIVO: Describir las características de la población afectada y los retrasos que contribuyeron a la mortalidad materna, secundaria a los trastornos hipertensivos del embarazo. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo efectuado con base en la vigilancia epidemiológica de casos centinela de muertes maternas tempranas de mujeres residentes en Antioquia, Colombia, durante el embarazo, el parto y los 42 días siguientes a éste ocurridas en el periodo 2012-2020. Se creó una base de datos en Microsoft Access 2007 (Microsoft, Redmond, WA, USA) y los datos se analizaron en Microsoft Excel y SPSS versión 22. RESULTADOS: Se registraron 266 muertes maternas, de las que 38 fueron secundarias a trastornos hipertensivos del embarazo. La eclampsia fue causa de 15 fallecimientos; 12 por síndrome HELLP, 9 por hemorragia intracerebral y 2 por desprendimiento prematuro de placenta y coagulación intravascular diseminada. En 13 de los 38 casos no hubo una pauta adecuada del sulfato de magnesio, 19 no recibieron tratamiento antihipertensivo, que estaba indicado y 17 no tuvieron un control antihipertensivo adecuado. CONCLUSIÓN: La atención prenatal es una oportunidad decisiva para la detección, prevención y estratificación del riesgo. Todos los centros de atención obstétrica deben estar preparados para gestionar urgencias asociadas con los trastornos hipertensivos del embarazo. Los desenlaces mejoran con la aplicación de protocolos de emergencia estandarizados, organizados y la participación de equipos multidisciplinarios que garanticen una atención de calidad y un efecto positivo en la morbilidad y mortalidad materna susceptible de prevención.

Abstract OBJECTIVE: To describe the characteristics of the affected population and the delays that contributed to maternal mortality secondary to hypertensive disorders of pregnancy. MATERIALS AND METHODS: Descriptive and retrospective study based on the epidemiologic surveillance of sentinel cases of early maternal deaths of women residing in Antioquia, Colombia, during pregnancy, delivery and the 42 days after delivery occurring in the period 2012-2020. A database was created in Microsoft Access 2007 (Microsoft, Redmond, WA, USA), and data were analyzed in Microsoft Excel and SPSS version 22. RESULTS: There were 266 maternal deaths, of which 38 were secondary to hypertensive disorders of pregnancy. Eclampsia was the cause of 15 deaths; 12 due to HELLP syndrome, 9 due to intracerebral hemorrhage, and 2 due to placental abruption and disseminated intravascular coagulation. In 13 of the 38 cases, there was no adequate magnesium sulfate regimen, 19 did not receive indicated antihypertensive treatment, and 17 did not have adequate antihypertensive control. CONCLUSION: Antenatal care is a critical opportunity for detection, prevention, and risk stratification. All obstetric care centers should be prepared to manage emergencies associated with hypertensive disorders of pregnancy. Outcomes improve with the use of standardized, organized emergency protocols and the participation of multidisciplinary teams that ensure quality care and a positive impact on preventable maternal morbidity and mortality.

Short-term voluntary exercise enhances the activation of endogenous neural stem cells inintracerebral hemorrhage mice with hyperlipidemia / 西安交通大学学报(医学版)

【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67+, and doublecortin (DCX)+ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin+/Ki67+ cells decreased and Nestin+/DCX+ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin+/Ki67+ cells decreased but that of Nestin+/DCX+ cells further increased significantly. However, compared with ICH, the increase of Nestin+/DCX+ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.

Improvement effect and mechanism of calycosin on acute inflammatory injury secondary to intracerebral hemorrhage / 中国药房

OBJECTIVE To investigate the improvement effect and mechanism of calycosin （CA） on acute inflammatory injury secondary to intracerebral hemorrhage. METHODS Male C57BL/6 mice were injected with type Ⅶ collagenase into the basal ganglia to establish an intracerebral hemorrhage model， which were divided into sham-operation group（phosphate buffered saline instead of collagenase）， model group， and different CA dose groups（15，30，60，120 mg/kg）. Based on the modified neurological severity score （mNSS） to screen the intervention doses， the volume of intracerebral hemorrhage， brain water content， the expressions of ionized calcium-binding adaptor molecule 1 （Iba1） in brain tissue， Toll-like receptor 4 （TLR4） and its downstream inflammatory factors [tumor necrosis factor-α （TNF-α）， inducible nitric-oxide synthase （iNOS）， interleukin-1β （IL- 1β）] in brain tissue， and the apoptosis of cells in brain tissue were detected. Primary microglia were cultured in vitro， and the expressions of TLR4 and its downstream inflammatory factors were detected. Primary neurons and primary microglia were co- cultured in vitro， and the apoptosis of neurons was detected. RESULTS The doses of 30 mg/kg and 60 mg/kg were selected as intervention doses of CA for subsequent experiments. Compared with the sham-operation group， the mice in the model group had cerebral hemorrhage， the volume of cerebral hemorrhage and brain water content were significantly increased （P＜0.05）； the positive expression rate of Iba1 protein in brain tissue was significantly increased， and the relative expression levels of TLR4， TNF-α， IL-1β and iNOS protein in brain tissue were up-regulated significantly. The apoptosis rate also increased significantly （P＜0.05）. Compared with model group， the above indexes of the mice in the 30 and 60 mg/kg CA groups were significantly improved （P＜0.05）. CA significantlyreduced the relative expression levels of TLR4 and its downstream inflammatory factors in microglia， and reduced the apoptosis of neurons in the co-culture system of primary neurons and primary microglia （P＜0.05）. CONCLUSIONS CA can exert a protective effect on the brain， which may be related to relieving the secondary acute inflammatory injury after intracerebral hemorrhage by inhibiting TLR4-mediated inflammatory response.

Fatal intracranial bleedings in a viper bite: A case report / 中华创伤杂志(英文版)

Viper bite envenomation represents a significant occupational hazard among agricultural workers in India. The viper bite envenomation is usually suspected when a patient presents with predominant local symptoms at the bitten site, including pain, swelling, and necrosis. Further, systemic findings such as diffuse intravascular coagulation, hypotension, and shock may alert physicians of viper bite envenomation rather than a neurotoxic snake bite. However, cerebral complications are rare in viper bites but may potentially fatal. Central nervous system involvement in a viper bite is either due to neurotoxins or hemorrhagins present in the venom, which may induce cerebral thrombosis, ischemia, infarction, and hemorrhage. Here we present a case of a previously healthy adult male who succumbed to extensive subarachnoid, intracerebral, and intraventricular hemorrhages involving bilateral cerebral hemispheres following viper snake bite envenomation. This report highlights the importance of anticipating cerebral complications in viper bite envenomation, a rare occurrence. It also emphasizes the need for early antisnake venom administration to prevent and control systemic envenomation and its complications.

Association between polarization status of microglia/macrophage in brain tissue and edema around hematoma in patients with acute cerebral hemorrhage / 新乡医学院学报

Objective To explore the correlation between polarization status of microglia/macrophages(MG/MP)in brain tissue and edema around hematoma in patients with acute cerebral hemorrhage.Methods A total of 52 patients with acute intracerebral hemorrhage admitted to Anyang People's Hospital from December 2020 to November 2022 were selected as the research subjects.All patients underwent craniotomy to remove hematoma,and the normal brain tissue in the cortical area that was not invaded by the hematoma and the fragmented brain tissue around the hematoma(brain tissue around the hematoma)on the surgical pathway were obtained.The expression levels of inflammatory factors such as interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),IL-10 and transforming growth factor-β(TGF-β)protein in brain tissue were detected by Western blot.The expression levels of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue were detected by fluorescence quantitative polymerase chain reaction.The levels of M1-type and M2-type MG/MP in brain tissue was detected by immunofluorescence confocal technique.CT images data of patients before operation were collected and the relative-erihema-tomal edema(r-PHE)was calculated.The patients were divided into high r-PHE group(2.0≤ r-PHE＜2.5)and low r-PHE group(1.5＜r-PHE＜2.0)according to r-PHE.The relative expression of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β mRNA in brain tissue around the hematoma of patients between the high r-PHE group and the low r-PHE group was compared.Results The relative expressions of IL-1 β,IL-6,TNF-α protein and mRNA in brain tissue around the hematoma were significantly higher than those in the normal brain tissues(P＜0.05),but there was no significant difference in the relative expressions of IL-10 and TGF-β protein and mRNA between the brain tissue around the hematoma and the normal brain tissue(P＞0.05).The levels of M1 type and M2 type MG/MP in the brain tissue around the hematoma were significantly higher than those in normal brain tissue(P＜0.05).The relative expressions of IL-1β,IL-6 and TNF-α mRNA in the brain tissue around the hematoma of patients in the high r-PHE group were significantly higher than those in the low r-PHE group(P＜0.05),and there was no significant difference in the relative expressions of TGF-β and IL-10 mRNA in the brain tissue around the hematoma of patients between the two groups(P＞0.05).Conclusion The levels of pro-inflammatory factors and M1-type MG/MP are increased in the brain tissue around the hematoma in patients with acute cerebral hemorrhage,and the degree of polarization of M1-type MG/MP is consistent with the degree of edema around hematoma after cerebral hemorrhage.

CiteSpace-based visual analysis of research progress on intracerebral hemorrhage-related signaling pathways in recent 10 years / 中风与神经疾病杂志

@#Objective To explore the hotspots and trend of research on the signaling pathways of intracerebral hemorrhage in the past 10 years through bibliometrics and visual analysis. Methods We used CiteSpace to perform bibliometrics and visual analysis on relevant articles published in the recent 10 years， which were obtained from the Science Citation Index Expanded database of the Web of Science Core Collection. Results According to visual analysis of 796 pieces of literature on intracerebral hemorrhage-related signaling pathways， there is a growing number of papers published in this field. China was the country with the largest number of papers published. Loma Linda University was the institution with the largest number of papers published. The funding institution sponsoring most in this field was the National Natural Science Foundation of China. The keyword analysis showed that the research focused on inflammatory reactions， oxidative stress， microRNA gene expression， nuclear factor-kappa B signaling pathways， extracellular regulated protein kinase 1/2 signaling pathways， the lipid-signaling molecule sphingosine-1-phosphate， and scalp acupuncture therapy. Conclusion CiteSpace-based visual analysis can directly display the research hotspots and trend of intracerebral hemorrhage-related signaling pathways， providing new insights into the treatment and prevention of intracerebral hemorrhage.

Research advances in the pyroptosis signaling pathway after intracerebral hemorrhage / 中风与神经疾病杂志

@#Pyroptosis is an important mechanism leading to secondary brain injury （SBI） after intracerebral hemorrhage （ICH）， which can be classified into the inflammasome-dependent classical pyroptosis pathway and the caspase-4/5/11-dependent non-classical pyroptosis pathway. GSDMD and GSDME of the gasdermin family are the key effectors of pyroptosis and bind to lipids on cell membrane to induce the formation of membrane pore. Interleukin-1β/-18 is a downstream inflammatory factor that mediates inflammatory injury after pyroptosis. This article reviews the key proteins in the pyroptosis pathway and the mechanism of action of the pyroptosis signaling pathway after ICH.

NF-κB-induced activation of NLRP3 inflammasome by LCN2 after intracerebral hemorrhage in rats / 中风与神经疾病杂志

@#Objective To investigate the mechanism of the elevated expression of LCN2 during intracerebral hemorrhage(ICH) and its involvement in inflammatory response after hemorrhage. Methods Male Sprague-Dawley rats were given an injection of autologous arterial blood(100 μl) at the basal ganglia,and the rats in the control group were given an injection of an equal volume of normal saline using the same surgical procedure. Ventricular injection of the NF-κB-specific inhibitors parthenolide and BAY11-7082 was performed for pretreatment,and after transfection with scrambled LCN2RNA or LCN2 siRNA,the levels of NLRP3,ASC,and cleaved caspase-1 were measured as the indicators for the status of inflammasome activation. Western blot,RT-PCR,and immunohistochemistry were used to measure the protein and mRNA expression levels of LCN2.Results Western blotting showed that there was a significant increase in the protein expression level of LCN2 in the ipsilateral basal ganglia on days 1,3,and 7 after hemorrhage and a significant reduction in this level on day 14.On day 3 after intracerebral hemorrhage,the protein expression level of LCN2 in the ipsilateral side was 71 times higher than that in the contralateral side(2.70±0.46 vs 0.04±0.01,P<0.001) and was 84 times higher than that in the control group(0.92±0.14 vs 0.01±0.01,P<0.001). Pretreatment with the NF-κB-specific inhibitors parthenolide and BAY11-7082 could inhibit the expression of LCN2.There were significant increases in the protein expression levels of NLRP3,ASC,and cleaved caspase-1 after transfection with scrambled siRNA,and LCN2 siRNA significantly reduced the expression of these inflammasome-associated proteins. Conclusion This study suggests that iron release after ICH can induce the expression of LCN2,and LCN 2 may play an important role in the inflammatory process after hemorrhage.

Expression of serum macrophage migration inhibitory factor and Tau protein in patients with severe hypertensive intracerebral hemorrhage and their relationships with clinical outcome / 中风与神经疾病杂志

@#Objective To explore the expression levels of serum macrophage migration inhibitory factor(MIF) and Tau protein in patients with severe hypertensive intracerebral hemorrhage(HICH),and analyze the relationships between their levels and patient outcome,and to provide a reference for clinical treatment of such patients. Methods We included 120 patients with severe HICH and 50 age-and sex-matched healthy controls from health examination in Ziyang Hospital of West China Hospital of Sichuan University from January 2019 to November 2022.The MIF and Tau protein levels of the two groups were compared. After a follow-up of more than half a year,the patients were divided into poor-prognosis group and good-prognosis group according to the defined criteria to compare their levels of MIF and Tau protein. The receiver operating characteristic(ROC) curve and Kaplan-Meier method were used to explore the critical values of MIF and Tau protein levels for patients with poor prognosis and the relationships with the clinical outcome of severe HICH. Results The levels of serum MIF and Tau protein in the patients with severe HICH were significantly higher than those in the control group(P<0.05). The poor-prognosis group showed significantly higher levels of serum MIF and Tau protein than the good-prognosis group(P<0.05). The ROC curve showed that the cutoff points of serum MIF and Tau protein levels for predicting poor prognosis were 64.43 ng/L and 216.25 pg/ml,respectively. The area under the curve for using MIF to predict poor prognosis was 0.815(95%CI=0.759-0.849),with sensitivity of 81.56% and specificity of 83.24%,and those values for using Tau protein to predict poor prognosis were 0.847(95%CI=0.764-0.831),82.26%,and 79.68%,respectively,all at high levels. Patients with serum MIF level <64.43 ng/L had significantly better survival than those with serum MIF level ≥ 64.43 ng/L(P<0.05 by log-rank test). Patients with serum Tau protein level<216.25 pg/ml had significantly better survival than those with serum Tau protein level ≥216.25 pg/ml(P<0.05 by log-rank test). Conclusion Patients with severe HICH had significantly higher serum MIF and Tau protein levels than healthy people. The patients with poor prognosis had significantly higher serum MIF and Tau protein levels than those with good prognosis. Serum MIF and Tau protein levels were closely related to the clinical outcome of the patients,which can be used as effective indicators to predict the prognosis of patients with HICH.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data / 中南大学学报(医学版)

OBJECTIVES@#Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms.@*METHODS@#Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants.@*RESULTS@#MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH.@*CONCLUSIONS@#There is a causal association and pleiotropic variants between GM and ICH.

Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage / 药物分析学报

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Relationship Between Neutrophil - albumin Ratio and Short - term Prognosis of Spontaneous Cerebral Hemorrhage / 医学研究杂志

Objective To investigate the relationship between neutrophil-to-albumin ratio(NAR)and severity and prognosis of patients with spontaneous intracerebral hemorrhage(sICH).Methods A total of 330 patients with sICH who met the enrollment criteria were included.They were divided into good prognosis group(mRS≤3,n =139)and poor prognosis group(mRS>3,n =191)according to the modified Rankin scale at 30days after onset.The clinical data of the two groups were analyzed by Univariate analysis,and the risk factors affecting the poor prognosis of sICH patients wereidentified by multivariate Logistic regression analysis.Spearman correlation analy-sis was used to explore the correlations between NAR and National Institute of Health stroke scale and intracerebral hemorrhage scale.The receiver operating characteristic(ROC)curve was further used to evaluate the predictive value of NAR in the early clinical prognosis of sICH patients.Results The NAR of patients with poor prognosis was significantly higher than that of patients with good prognosis[0.16(0.13,0.18)vs 0.22(0.19,0.28),P<0.001].Multivariate Logistic regression analysis showed that NAR was an independent risk factor for poor prognosis in patients with sICH after adjusting for confounding factors(OR =1.480,95%CI:1.320-1.521,P<0.001).NAR was moderately positively correlated with NIHSS(r =0.489,P<0.001)and ICH score(r =0.450,P<0.001).The area under the ROC curve of NAR was0.818(95%CI:0.771-0.865),indicating good prediction efficiency.Conclusion Elevated NAR on admission was associated with the severity of sICH,and NAR represents an independent factor associated with poor outcome in sICH patients.