Optimization of nursing interventions for postoperative mental status recovery in patients with cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Lung imaging characteristics in a patient infected with Elizabethkingia miricola following cerebral hemorrhage surgery: A case report

BACKGROUND Elizabethkingia miricola is a non-fermenting gram-negative bacterium,which was first isolated from the condensate of the Russian peace space station in 2003.Most studies on this bacterium have been carried out in the laboratory,and clinical case studies are rare.To date,a total of 6 clinical cases have been reported worldwide.CASE SUMMARY We present the first case of postoperative pulmonary infection in a patient with intracerebral hemorrhage due to Elizabethkingia miricola.The imaging character-istics of pulmonary infection were identified and the formulation and selection of the clinical treatment plan for this patient are discussed.CONCLUSION Elizabethkingia miricola infection is rare.When pulmonary infection occurs,computed tomography imaging may show diffuse distribution of a ground glass density shadow in both lungs,the air containing bronchial sign in local areas,thickening of bronchial vascular bundle,and pleural effusion.

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Cerebral venous sinus thrombosis presenting with subarachnoid hemorrhage and intracerebral hemorrhage:a case report

Objective:To explore the clinical and pathological characteristics of cerebral venous sinus thrombosis(CVST)with subarachnoid hemorrhage(SAH)and intracerebral hemorrhage(ICH),and to investigate the diagnosis,radiographic changes,and prognosis over the course of treatment.Methods:The clinical data and radiographic findings of a young male CVST patient,who presented with initial symptoms of SAH and ICH,were collected and analyzed.The relevant literature was also reviewed.Results:The patient had no specific clinical symptoms except for headache.The brain computed tomography(CT)scan revealed SAH,a high-density shadow in the right posterior fossa and cerebellar hemisphere,and ICH in the left frontal lobe.Magnetic resonance venography(MRV)further revealed bilateral thrombosis in the transverse and sigmoid sinuses.Conclusion:CVST with SAH and ICH is rare and difficult to diagnose.Careful radiological study and clinical analysis are important for the correct and early diagnosis of this condition.Anticoagulation therapy is considered the primary treatment for CVST.

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.

“Baihui”(DU20)-penetrating “Qubin”(GB7) acupuncture on blood–brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK Ⅱ/MLC 2 signaling pathway

Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

Postoperative Care for Patients with Hypertensive Intracerebral Hemorrhage

This article summarizes the postoperative care plan for patients with hypertensive intracerebral hemorrhage(HICH).Nursing strategies are analyzed in terms of the level of consciousness,pupil care,vital sign care,temperature care,complication care,and early rehabilitation care,with the goal of providing reference for follow-up care of HICH patients.

ATAT1 deficiency enhances microglia/macrophage-mediated erythrophagocytosis and hematoma absorption following intracerebral hemorrhage

MIcroglia/macrophage-mediated erythrophagocytosis plays a crucial role in hematoma clearance after intracerebral hemorrhage.Dynamic cytoskeletal changes accompany phagocytosis.However,whether and how these changes are associated with microglia/macrophage-mediated erythrophagocytosis remain unclear.In this study,we investigated the function of acetylatedα-tubulin,a stabilized microtubule form,in microglia/macrophage erythrophagocytosis after intracerebral hemorrhage both in vitro and in vivo.We first assessed the function of acetylatedα-tubulin in erythrophagocytosis using primary DiO GFP-labeled red blood cells co-cultured with the BV2 microglia or RAW264.7 macrophage cell lines.Acetylatedα-tubulin expression was significantly decreased in BV2 and RAW264.7 cells during erythrophagocytosis.Moreover,silencingα-tubulin acetyltransferase 1(ATAT1),a newly discoveredα-tubulin acetyltransferase,decreased Ac-α-tub levels and enhanced the erythrophagocytosis by BV2 and RAW264.7 cells.Consistent with these findings,in ATAT1-/-mice,we observed increased ionized calcium binding adapter molecule 1(Iba1)and Perls-positive microglia/macrophage phagocytes of red blood cells in peri-hematoma and reduced hematoma volume in mice with intracerebral hemorrhage.Additionally,knocking out ATAT1 alleviated neuronal apoptosis and pro-inflammatory cytokines and increased anti-inflammatory cytokines around the hematoma,ultimately improving neurological recovery of mice after intracerebral hemorrhage.These findings suggest that ATAT1 deficiency accelerates erythrophagocytosis by microglia/macrophages and hematoma absorption after intracerebral hemorrhage.These results provide novel insights into the mechanisms of hematoma clearance and suggest ATAT1 as a potential target for the treatment of intracerebral hemorrhage.

Serum vascular endothelial growth factor and cortisol expression to predict prognosis of patients with hypertensive cerebral hemorrhage

BACKGROUND Cerebral hemorrhage is a common and severe complication of hypertension in middle-aged and elderly men.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and cortisol(Cor)and the prognosis of patients with hypertensive cerebral hemorrhage.METHODS A hundred patients with hypertensive intracerebral hemorrhage were enrolled from January 2020 to December 2022 and assigned to the hypertensive intracerebral hemorrhage group.Another 100 healthy people who were examined at our hospital during the same period were selected and assigned to the healthy group.Peripheral venous blood was collected,and serum Cor and VGEF levels were measured through enzyme linked immunosorbent assay.RESULTS A statistically significant difference in serum Cor and VGEF levels was observed among patients with varying degrees of neurological impairment(P<0.05).Serum Cor and VGEF levels were significantly higher in the severe group than in the mild-to-moderate group.Cor and VEGF levels were significantly higher in patients with poor prognoses than in those with good prognoses.Multiple logistic regression analysis revealed that serum Cor and VGEF levels were independent factors affecting hypertensive intracerebral hemorrhage(P<0.05).CONCLUSION Cor and VGEF are associated with the occurrence and development of hypertensive cerebral hemorrhage and are significantly associated with neurological impairment and prognosis of patients.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage

Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Temporal dynamics of microglia-astrocyte interaction in neuroprotective glial scar formation after intracerebral hemorrhage

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to investigate 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.

Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage

Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell injury.Our findings reveal that WFA treatment alleviated ICH injury-induced ferroptosis and oxidative stress through activating the Nrf2/HO-1 pathway,which may highlight a potential role of WFA for the treatment of ICH.

Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

Piezo1 suppression reduces demyelination after intracerebral hemorrhage

Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.

Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage

Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.

Cyclophilin D-induced mitochondrial impairment confers axonal injury after intracerebral hemorrhage in mice

The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.