Clinical value of precise rehabilitation nursing in management of cerebral infarction

BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction

BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.METHODS Between January 2020 and December 2023,we treated 98 cases of elderly acute insula,patients with cerebral infarction in the cerebral infarction acute phase(3-4 weeks)and for the course of 6 months in Montreal Cognitive Assessment Scale(MoCA)for screening of cognition.Notably,58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group,respec-tively.In patients with cerebral infarction,magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions,the relationship between the parts of the infarction volume,and analysis of acute insula cognitive disorder in elderly patients with cerebral RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment(P<0.05).The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group,and the difference was statistically significant(P<0.05).The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group(P<0.05).In the cognitive impairment group,the infarct volumes in the basal ganglia,thalamus,and mixed lesions were negatively correlated with the total MoCA score,with correlation coefficients of-0.67,-0.73,and-0.77,respectively.CONCLUSION In elderly patients with acute insular infarction,infarction in the basal ganglia,thalamus,and mixed lesions were more likely to lead to cognitive dysfunction than in other areas,and patients with large infarct volumes were more likely to develop cognitive dysfunction.The infarct volume in the basal ganglia,thalamus,and mixed lesions was significantly negatively correlated with the MoCA score.

Evolving of treatment options for cerebral infarction

In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thrombolysis,aspirin is the most effective treatment for CI.Edaravone,a free radical scavenger,reduces endothelial cell damage and delays neuronal cell death.Aspirin plus edaravone mitigates damage to brain tissue by different mechanisms,thereby expediting the reinstation of neurological function.However,the nephrotoxic effect of edaravone,along with gastrointestinal bleeding associated with aspirin,may restrict this combination therapy.Although clinical studies have demonstrated the efficacy of thrombolytic therapy and mechanical thrombectomy,patients receiving these treatments experience modest efficacy and many adverse events.Moreover,interest in exploring natural medicines for CI is increasing,and they appear to have a high potential to protect against CI.The evolution of therapeutic strategies is expected to improve clinical outcomes of patients with CI.

Magnetic resonance imaging combined with serum endolipin and galactagoglobin-3 to diagnose cerebral infarction in the elderly with diabetes mellitus

BACKGROUND Magnetic resonance imaging(MRI)combined with serum endothelin and galactagoglobin-3(Gal-3)can improve the clinical diagnosis of diabetes mellitus complicated with cerebral infarction.AIM To analyze the clinical value of MRI combined with serum endolipin and Gal-3 for the diagnosis of cerebral infarction in the elderly with diabetes mellitus.METHODS One hundred and fifty patients with acute cerebral infarction hospitalized between January 2021 and December 2023 were divided into two groups according to comorbid diabetes mellitus,including 62 and 88 cases in the diabetic and nondiabetic cerebral infarction groups.Serum samples were collected to detect the expression of serum endolipoxins,and Gal-3,and cranial MRI was performed at admission.Differences between the two groups were compared to analyze the diagnostic value of these parameters.RESULTS Serum endolipin and Gal-3 expression were higher in the diabetic cerebral infarction group(P<0.05).The arterial wall area,vessel area,normalized wall index,and lumen stenosis rate were higher in the diabetic cerebral infarction group,while the rate of arterial lumen moderate and severe stenosis was 48.39% higher(36.36%,P<0.05).The percentage of large(29.03%)and multiple infarcts(33.87%)in the diabetic cerebral infarction group was higher(13.64% and 20.45%),and the incidence rate of lacunar infarcts was lower(37.10%vs 65.91%)(P<0.05).The total incidence of arterial plaque in patients in the diabetic cerebral infarction group was 96.77% higher(69.32%),while the incidence of necrotic lipid core plaque was 58.06%higher(26.14%)(P<0.05).Receiver operating characteristic curve analysis was performed to assess the diagnosis utility of these techniques.MRI in combination with serum endoglin and Gal-3 had the highest area under the curve,the Yoden index,sensitivity and specificity(P<0.05).CONCLUSION The expression of serum endolipin and Gal-3 in elderly patients with diabetes mellitus with cerebral infarction showed an elevated trend,and the degree of luminal stenosis was severe.MRI predominantly revealed large and multiple infarct foci.This combined index examination can improve the clinical diagnosis of diabetes mellitus combined with cerebral infarction.

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction

BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI patients.METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two groups.Finally,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),respectively.RESULTS Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after treatment.CONCLUSION Aspirin plus edaravone had a good curative effect on CI.It can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.

The Prognostic Value of Red Cell Distribution Width in Critically Ill Cerebral Infarction Patients:A Retrospective Cohort Study

Objective:Red blood cell distribution width(RDW)has been utilized as a prognostic indicator for mortality risk assessment in cardiovascular and cerebrovascular patients.Nevertheless,the prognostic significance of RDW in critically ill patients with cerebral infarction is yet to be investigated.The objective of this study is to examine the association between RDW and the risk of all-cause mortality in cerebral infarction patients admitted to the intensive care unit(ICU).Method:A retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.2(MIMIC-IV)intensive care dataset for data analysis.The main results were the all-cause mortality rates at 3 and 12 months of follow-up.Cumulative curves were plotted using the Kaplan-Meier method,and Cox proportional hazards analysis was used to examine the relationship between RDW and mortality rates in critically ill cerebral infarction patients.Results:The findings indicate that RDW serves as a significant prognostic factor for mortality risk in critically ill stroke patients,specifically at the 3 and 12-month follow-up periods.The observed correlation between increasing RDW levels and higher mortality rates among cerebral infarction patients further supports the potential utility of RDW as a predictive indicator.Conclusion:RDW emerges as an independent predictor of mortality risk during the 3 and 12-month follow-up periods for critically ill patients with cerebral infarction.

Application Effect of Early Rehabilitation Nursing in Elderly Cerebral Infarction Patients with Dysphagia

Objective:To observe the application effect of early rehabilitation nursing in elderly cerebral infarction patients with dysphagia.Methods:120 cases of elderly cerebral infarction patients with dysphagia were divided into 60 cases in the control group and 60 cases in the observation group by the double-blind method,and conventional nursing and early rehabilitation nursing were implemented respectively.Swallowing function,quality of life,adverse events,and nursing satisfaction were compared before and after nursing care.Results:After nursing,the swallowing function score of the observation group(1.01±0.18 points)was lower than that of the control group,and the quality of life score(160.63±9.95 points)was higher than that of the control group(P<0.05);the incidence rates of aspiration and aspiration pneumonia in the observation group(5.00%and 3.33%)were lower than that of the control group(P<0.05);the total nursing satisfaction of the observation group(98.33%)was higher than that of the control group(P<0.05).Conclusion:Early rehabilitation nursing can reduce the degree of dysphagia in elderly patients with cerebral infarction,reduce the incidents of aspiration and aspiration pneumonia,and improve the quality of life,with high nursing satisfaction.

The Effect of Different Hyperbaric Oxygen Treatment Time Windows on Neurological Function and Prognosis in Acute Cerebral Infarction

Objective:To observe the effects of different hyperbaric oxygen treatment time windows on the prognosis and neurological function of acute cerebral infarction.Method:160 patients with acute cerebral infarction admitted to Xiangyang Central Hospital in Hubei Province were randomly divided into four groups,each with 40 cases,using a random number table method.According to the 2017 guidelines for the treatment of cerebral infarction,the control group received routine treatment for acute cerebral infarction;On the basis of the control group,patients in Group A received hyperbaric oxygen therapy within 48 hours of onset;Group B patients receive hyperbaric oxygen therapy within 3-6 days of onset;Group C patients receive hyperbaric oxygen therapy within 7-12 days of onset.Observe the efficacy,recurrence,and neurological function recovery of four groups of patients after treatment.Result:There was no statistically significant difference in the National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI)scores among the four groups before treatment(P>0.05).There were statistically significant differences in NIHSS and BI scores between 14 and 30 days after treatment and before treatment(F=16.352,27.261,11.899,28.326,P<0.05).At 14 and 30 days after treatment,the NIHSS score in Group A decreased compared to the control group,Group B,and Group C,while the BI score increased compared to the control group,Group B,and Group C,with statistical significance(P<0.05).There was no statistically significant difference in NIHSS and BI scores between Group C and the control group after treatment(P>0.05).After 30 days of treatment,the total effective rate of Group A was higher than that of the control group and Group C,and the difference was statistically significant(X2=6.135,P<0.05).The one-year recurrence rate of Group A and Group B is lower than that of Group C and the control group,and the difference is statistically significant(X2=8.331,P<0.05).There was no statistically significant difference in adverse reactions among the four groups(P>0.05).Conclusion:Patients with acute cerebral infarction who receive hyperbaric oxygen therapy within 48 hours can improve neurological function and reduce the recurrence rate.The efficacy of receiving hyperbaric oxygen therapy within 7-12 days of onset is equivalent to that of not receiving hyperbaric oxygen therapy.

Analysis of the Effect of Limb Rehabilitation Therapy Combined with Transcranial Magnetic Stimulation Therapy on Muscle Activity in Patients with Upper Limb Dysfunction After Cerebral Infarction

Objective:To analyze the effect of limb rehabilitation therapy combined with transcranial magnetic stimulation therapy on muscle activity in patients with upper limb dysfunction after cerebral infarction(CI).Methods:320 patients with upper limb dysfunction after CI were selected,all of whom were treated in our hospital between June 2021 and June 2023.They were randomly grouped according to the lottery method into the control group(limb rehabilitation therapy,160 cases)and the intervention group(transcranial magnetic stimulation therapy+limb rehabilitation therapy,160 cases).The upper limb function scores,neuro-electrophysiological indicators,daily living ability scores,and quality of life scores of the two groups were compared.Results:Compared with the control group,upper limb function scores and daily living ability scores in the intervention group were higher after treatment,and the neuro-electrophysiological indicators of the intervention group were lower after treatment(P<0.05).Conclusion:Transcranial magnetic stimulation therapy combined with limb rehabilitation therapy has significant effects in patients with upper limb dysfunction after CI and is worthy of promotion and application.

Impact of early refined nursing program on prognosis of middleaged and elderly patients with cognitive dysfunction combined with cerebral infarction

BACKGROUND Cerebral infarction is a local or extensive necrosis of brain tissue.Subsequently,the corresponding neurological deficits appear.The incidence of cerebrovascular diseases in China is increasing gradually.After the onset of cerebrovascular disease,the most common sequelae include movement disorders,language disorders,and cognitive dysfunction.AIM To investigate the effect of early refined nursing program on the prognosis of middle-aged and elderly patients with cerebral infarction combined with cognitive dysfunction.METHODS A retrospective study was conducted to divide 60 patients with cerebral infarction and cognitive impairment into an experimental group(n=32)and a control group(n=28).The experimental group received early intensive care every day,and the control group received daily routine care.The scores of the Mini-Mental State Examination(MMSE)and the Trail Making Test(TMT),as well as the latency and amplitude of the event-related potential P300,were used as main indicators to evaluate changes in cognitive function,and changes in BDNF,TGF-β,and GDNF expression were used as secondary indicators.RESULTS Both groups experienced notable enhancements in MMSE scores,with the experi-mental group demonstrating higher scores than the control group(experimental:28.75±2.31;control:25.84±2.87).Moreover,reductions in TMT-A and TMT-B scores were observed in both groups(experimental:TMT-A 52.36±6.18,TMT-B 98.47±10.23;control:TMT-A 61.48±7.92,TMT-B 112.63±12.55),with the experimental group displaying lower scores.P300 Latency decreased(experimental:270.63 ms±14.28 ms;control:285.72 ms±16.45 ms),while amplitude increased(experimental:7.82μV±1.05μV;control:6.35μV±0.98μV)significantly in both groups,with superior outcomes in the experimental cohort.Additionally,the levels of the growth factors BDNF,TGF-β1,and GDNF surged(experimental:BDNF 48.37 ng/mL±5.62 ng/mL,TGF-β152.14 pg/mL±4.28 pg/mL,GDNF 34.76 ng/mL±3.89 ng/mL;control:BDNF 42.58 ng/mL±4.73 ng/mL,TGF-β146.23 pg/mL±3.94 pg/mL,GDNF 30.25 ng/mL±2.98 ng/mL)in both groups,with higher levels in the experimental group.CONCLUSION For middle-aged and elderly patients with cerebral infarction and cognitive dysfunction,early refined nursing can significantly improve their cognitive function and prognosis.

Cerebral pseudoinfarction due to venoarterial extracorporeal membrane oxygenation:A case report

BACKGROUND Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation(VA-ECMO),with most patients requiring sedation and intubation,limiting the assessment of neurological function.Therefore,we must rely on advanced neuroimaging techniques,such as computed tomography angiography(CTA)and computed tomography perfusion(CTP).Because ECMO changes the normal blood flow pattern,it may interfere with the contrast medium in some special cases,leading to artifacts and ultimately misleading clinical decisions.CASE SUMMARY A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to presentation.The patient was treated with VA-ECMO after sudden cardiac and respiratory arrest at a local hospital.For further treatment,the patient was transferred to our hospital.The initial consciousness assessment was not clear,and routine CTP was performed to understand the intracranial changes,which suggested a large area of cerebral infarction on the right side;however,the cerebral oxygen was not consistent with the CTP results,and the reexamination of CTA still suggested a right cerebral infarction.To identify this difference,bedside transcranial Doppler was performed,and the blood flow on both sides was different.By reducing the ECMO flow,CTP reexamination showed that the results were normal and consistent with the clinical results.On day 3,the patient was alert and showed good limb movements.CONCLUSION In patients with peripheral VA-ECMO,cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.

Revisiting cerebral endothelial cells in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

Successful emergency surgical intervention in acute non-STsegment elevation myocardial infarction with rupture:A case report

BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with non-STEMI.Types of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle rupture.The FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be effective.Ventricular septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair options.CASE SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary angiography.Prompt resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient recovery.CONCLUSION This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic surgery.Although cerebral fat embolism(CFE)as a complication is rare,it carries serious health risks.CASE SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling surgery.After the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided weakness.Comprehensive physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon admission.The clinical diagnosis was acute cerebral embolism following facial fat filling surgery.Treatment included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb function.The patient showed a significant improvement in symptoms after 2 weeks of treatment.She recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of headache.CONCLUSION Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial reconstruction.To prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

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.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.