Advances in surgical treatment of intraventricular hemorrhage

Intraventricular hemorrhage(IVH)is a dangerous acute cerebrovascular disease.The 30-day mortality rate of patients with IVH is 5 times that of patients with cerebral hemorrhage.In recent years,more and more studies have shown that timely clearance of intraventricular hematoma is closely related to good prognosis.The advantages of surgical intervention in patient management are impressive.This article briefly reviews the positive advances in the surgical treatment of IVH such as external ventricular drainage(EVD)combined with intraventricular fibrinolysis(IVF)and continuous lumbar cistern drainage(LCD),as well as their safety and efficacy,especially the remarkable role of neuroendoscopy in the removal of intraventricular hematomas.

Interobserver reliability between pediatric radiologists and residents in ultrasound evaluation of intraventricular hemorrhage in premature infants

BACKGROUND Germinal matrix intraventricular hemorrhage(IVH)may contribute to significant morbidity and mortality in premature infants.Timely identification and grading of IVH affect decision-making and clinical outcomes.There is possibility of misinterpretation of the ultrasound appearances,and the interobserver variability has not been investigated between radiology resident and board-certified radiologist.AIM To assess interobserver reliability between senior radiology residents performing bedside cranial ultrasound during on-call hours and pediatric radiologists.METHODS From June 2018 to June 2020,neonatal cranial ultrasound examinations were performed in neonatal intensive care unit.Ultrasound findings were recorded by the residents performing the ultrasound and the pediatric attending radiologists.RESULTS In total,200 neonates were included in the study,with a mean gestational age of 30.9 wk.Interobserver agreement for higher grade(Grade III&IV)IVH was excellent.There was substantial agreement for lower grade(Grade I&II)IVH.CONCLUSION There is strong agreement between radiology residents and pediatric radiologists,which is higher for high grade IVHs.

Endoscopic Surgery versus External Ventricular Drainage Surgery for Severe Intraventricular Hemorrhage

The efficacy and applied value of endoscopic hematoma evacuation vs. external ventricular drainage (EVD) in the treatment of severe ventficular hemorrhage (IVH) were explored and compared.From Jan.2015 to Dec.2016,the clinical data of 42 cases of IVH were retrospectively analyzed,including 18 patients undergoing endoscopic hematoma evacuation (group A),and 24patients receiving EVD (group B).The hematoma clearance rate was calculated by 3D Slicer software,and complications and outcomes were compared between the two groups.There were no significant differences in age,sex and Graeb score between groups A and B (P>0.05).The hematoma clearance rate was 70.81%±27.64% in group A and 48.72%±36.58% in group B with a statistically significant difference (P<0.05).The operative time in groups A and B was 72.45±25.26 min and 28.54±15.27min,respectively (P<0.05).The Glasgow Coma Scale (GCS) score increased from 9.28±2.72 at baseline to 11.83±2.91 at 1 week postoperatively in group A,and from 8.25±2.62 at baseline to 10.79±4.12 at 1 week postoperatively in group B (P<0.05).The length of hospital stay was 12.67±5.97 days in group A and 17.33±8.91 days in group B with a statistically significant difference (P<0.05).The GOS scores at 6 months after surgery were 3.83±1.12 in group A,and 2.75±1.23 in group B (P<0.05). These results suggested that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate,fewer complications and better outcomes in the treatment of severe IVH,indicating it is a safe,effective and promising approach for severe IVH.

MODIFIED GRAEB CRITERIA FOR PREDICTING THE POST-HEMORRHAGIC HYDROCEPHALUS IN INTRAVENTRICULAR HEMORRHAGE

Objective To set up a new grading system of intraventricular hemorrhage (IVH) and determine the value of predicting the probability of post-hemorrhagic hydrocephalus (PHH) in IVH. Methods We first modified the Graeb criteria, then compared the value of prediction for PHH assessed by the Graeb criteria with the modified Graeb criteria. One hundred and thirty one IVH patients were divided into two groups: the upper group (n=67) and the lower group (n=64). Gold standard of PHH was assessed by CT scan or by out-drainage. The diagno-stic parameters such as sensitivity (SE), specificity (SP) were analyzed. In the cutoff point of SE and SP curves, diagnostic efficiency (DE), and Kappa value (K) were analyzed. The probability of PHH was estimated by binary logistic regressions. Results In all ventricular group, to Graeb criteria in the cutoff point, SE, SP, and K was 0.78, 0.84, and 0.60; and to modified Graeb criteria SE, SP, and K was 0.90, 0.84, and 0.74 respectively. The probability of PHH from point of 3-12 was 0.011, 0.032, 0.085, 0.212, 0.435, 0.689, 0.865, 0.949, 0.981, and 0.994 respectively according to modified Graeb criteria. Conclusion The modified Graeb criteria combined with logistic regression were useful methods to assess the severity of IVH and to predict the probability of PHH in IVH.

Endoscopic surgery for intraventricular hemorrhage:A comparative study and single center surgical experience

BACKGROUND Intraventricular hemorrhage is a neurosurgical emergency,and a dangerous condition associated with high morbidity and mortality.Previously,hematoma evacuation is generally executed by external intracranial drainage(EVD)or surgical evacuation.Nowadays,endoscopic evacuation is emerging as a good alternative because it brings relatively less invasion and injury.However,successful endoscopic evacuation requires skilled manipulation of endoscopic devices and the evidence supporting its efficacy differs in different reports.AIM To improve the technique usage and provide more evidence of endoscopic evacuation efficacy,we summarize our surgical experience and compared the outcomes of the endoscopic evacuation with EVD using real-world data.METHODS We retrospectively studied 96 consecutive patients with intraventricular hemorrhage who underwent either endoscopic surgery(n=43)or non-endoscopic surgery(n=53)for hemorrhage evacuation between November 2013 and September 2019 in our center.Patients’conditions prior to and after the operation were evaluated and analyzed to assess the efficacy of the operation.The consciousness status improvement and perioperative in-hospital parameters in the two types of operation groups were assessed and compared.RESULTS Patients in the endoscopic and non-endoscopic groups presented with a similar state of consciousness,with a comparable Glasgow Coma Scale(GCS)index.The average operation time of the endoscopic group was longer than that of the nonendoscopic group(median 2.42 h vs 1.08 h,P<0.001).Although the endoscopic group was older and had a baseline Graeb score that indicated more severe hemorrhage than the non-endoscopic group(Graeb median:Endoscopic group=9 vs non-endoscopic group=8,P=0.023),the clearance rate of hematoma was as high as 60.5%.Both the endoscopic and non-endoscopic groups showed an improved GCS index after surgery.However,this improvement was more marked in patients in the endoscopic group(median improvement of GCS index:Endoscope group=4 vs non-endoscopic group=1,P<0.001).Additionally,the endoscopic group had a lower Graeb score than the non-endoscopic group after the operation.The intensive care unit stay of the endoscopic group was significantly shorter than that of the non-endoscopic group(median:endoscopic group=6 d vs non-endoscope group=7 d,P=0.017).CONCLUSION Endoscopic evacuation of intraventricular hemorrhage was generally an effective and efficient way for hemorrhage evacuation,and contributed remarkably to the improvement of consciousness in patients with intraventricular hemorrhage.

Outcomes of high-grade aneurysmal subarachnoid hemorrhage patients treated with coiling and ventricular intracranial pressure monitoring

BACKGROUND High-grade aneurysmal subarachnoid hemorrhage is a devastating disease with a low favorable outcome.Elevated intracranial pressure is a substantial feature of high-grade aneurysmal subarachnoid hemorrhage that can result to secondary brain injury.Early control of intracranial pressure including decompressive craniectomy and external ventricular drainage had been reported to be associated with improved outcomes.But in recent years,little is known whether external ventricular drainage and intracranial pressure monitoring after coiling could improve outcomes in high-grade aneurysmal subarachnoid hemorrhage.AIM To investigate the outcomes of high-grade aneurysmal subarachnoid hemorrhage patients with coiling and ventricular intracranial pressure monitoring.METHODS A retrospective analysis of a consecutive series of high-grade patients treated between Jan 2016 and Jun 2017 was performed.In our center,followed by continuous intracranial pressure monitoring,the use of ventricular pressure probe for endovascular coiling and invasive intracranial pressure monitoring in the acute phase is considered to be the first choice for the treatment of high-grade patients.We retrospectively analyzed patient characteristics,radiological features,intracranial pressure monitoring parameters,complications,mortality and outcome.RESULTS A total of 36 patients were included,and 32(88.89%)survived.The overall mortality rate was 11.11%.No patient suffered from aneurysm re-rupture.The intracranial pressure in 33 patients(91.67%)was maintained within the normal range by ventricular drainage during the treatment.A favorable outcome was achieved in 18 patients(50%)with 6 mo follow-up.Delayed cerebral ischemia and Glasgow coma scale were considered as significant predictors of outcome(2.066 and-0.296,respectively,P<0.05).CONCLUSION Ventricular intracranial pressure monitoring may effectively maintain the intracranial pressure within the normal range.Despite the small number of cases in the current work,high-grade patients may benefit from a combination therapy of early coiling and subsequent ventricular intracranial pressure monitoring.

Adrenal Hemorrhage as a Rare Cause of Neonatal Anemia Associated with Hydrocephalus Secondary to Intraventricular Hemorrhage—A Case Report

Neonatal adrenal hemorrhage is frequently associated with birth trauma, perinatal asphyxia, intrauterine infection, coagulation defects and thromboembolism. It has varied clinical presentation depending on degree of hemorrhage and amount of adrenal cortex compromised by hemorrhage. The most common clinical presentations are persistent jaundice and flank mass. We report a case of left sided adrenal hemorrhage in a breech delivered male neonate with perinatal asphyxia presented with anemia and fever. On further evaluation, he was also having moderate communicating hydrocephalus secondary to intraventricular hemorrhage. The adrenal hemorrhage was managed conservatively. Subsequent abdominal ultrasound showed resolving adrenal hemorrhage. Right ventriculoperitoneal shunt was done for hydrocephalus. Postoperative course was uneventful. The patient is asymptomatic at follow-up.

Restoration of an injured lower dorsal ascending reticular activating system in a patient with intraventricular hemorrhage

The ascending reticular activating system（ARAS）plays a key role in the control of arousal and awareness for consciousness（Paus,2000;Zeman,2001;Van der Werf et al.,2002;Weiss et al.,2007;Siposan and Aliu,2014）.It is well known that the ARAS originates from the reticular formation（RF）of the brainstem,and connects to the cerebral cortex via intralaminar to the cerebral cortex （Paus, 2000; Zeman, 2001; Van der Werf et al., 2002; Yeo et al., 2013; Jang and Kwon, 2015）. The hypothalamus is involved in the regulation of sleep and awareness which is associated with the main timekeeper of consciousness （Lin, 2000; Lin et al., 2011）.

MECHANISM OF PATHOLOGICAL CHANGES OF INTRAVENTRICULAR HEMORRHAGE IN DOGS

Objective To probe the mechanism of pathological changes of intraventricular hemorrhage(IVH). Methods The evaluation of neurological status,serial CT scans and pathological examination were applied on the canine model of IVH. The ventricular volume and blood clot volume were measured based on the CT images. Results The normal adult canine ventricle tend to be slitlike. After injection, the ventricle was obviously dilated by the blood clot. The linear regression of ventricular volume against blood clot volume was significant in the first week. From then on, however, while the clots continued to shrink, the ventricular volume showed progressive enlargement. The clots were lysed completely within 3 to 4 weeks. The linear regression of the degree of ventricular dilatation against the first clot volume was also significant. In the pathological examination, we found the ependymal lining of ventricular system was destroyed and neurons in the subependymal areas developed acidophil necrosis, which was prominent around Sylvian aqueduct. Conclusion Hemorrhagic ventricular dilatation(HVD) is a prominent feature of IVH and also is a strong indicator for poor prognosis. Ischemic changes of periventricular neurons in some important structures may be the most direct cause for poor outcome of IVH. It may be induced by periventricular vascular structures compressed by HVD, increased intracranial pressure, cerebral vasospasm and others.

Evacuation of Spontaneous Thalamic and Intraventricular Hemorrhage under the Operating Microscope Improves Mortality Compared with External Ventricular Drainage——Mini-Cranioctomy for Thalamic and Ventricular Hemorrhage

We performed direct hematoma evacuation of thalamic and intraventricular hemorrhage using mini-craniotomy in recent years. The present study evaluated the outcome and complications in 18 patients with spontaneous thalamic and intraventricular hemorrhage treated by mini-craniotomy hematoma evacuation with external ventricular drainage and 24 patients treated by only external ventricular drainage. Patients treated by mini-craniotomy were less likely to require days of ventricular drainage settlement, had a less suffering meningitis, had good hematoma evacuation rate and had a less mortality rate compared with those undergoing only external ventricular drainage. Frontal mini-craniotomy microscope operation is a simple and effective method for hematoma evacuation that causes fewer complications.

Prevalence, Risk Factors and Intra-Hospital Outcomes Relating to Peri-Intraventricular Hemorrhage in Premature Newborns of Gestational Age Less than 34 Weeks

Peri-intraventricular hemorrhage is one of the main causes of neurological impairment in premature newborns. To control their risk factors is necessary in view of the increasing survival of extreme preterm infants. Objective: To evaluate the prevalence of peri-intraventricular hemorrhage in premature newborns, identify the risk factors and observe the frequencies of intra-hospital outcomes of interests. Methods: This study was done in Brazil. This was an observational, analytical longitudinal and prospective study. The subjects included were newborns of gestational age less than 34 weeks who were admitted to two public hospitals between May and November 2015. To assess possible associated factors, obstetric, perinatal and neonatal data were analyzed (chorioamnionitis, antenatal corticosteroids, gestational age, newborn weight, Apgar score at 1 and 5 minutes, resuscitation in the delivery room, surfactant in the delivery room, newborn transferred from another hospital, respiratory distress syndrome: RDS, sepsis, umbilical vein catheterization, assisted ventilation, exogenous surfactant in the Neonatal ICU, use of sodium bicarbonate, inotropic agents, adrenaline, volume expanders and blood products). The hospital outcomes studied were assisted ventilation time, hospital stay and death. The data analysis was performed by chi-square test or Fisher’s test, with a significance level of 5%. Results: Out of 156 newborns, 46 (29.9%) presented peri-intraventricular hemorrhage and 28.2% of these had a severe form of the disease. There were significant associations (p < 0.05) with the following risk factors: gestational age, birth weight, low Apgar score, delivery room resuscitation, RDS, surfactant use, sepsis, packed red blood cell transfusion, mechanical ventilation and umbilical vein catheterization. The newborns with peri-intraventricular hemorrhage presented longer times on assisted ventilation, longer hospital stays and higher risk of death. Conclusion: The prevalence of peri-intraventricular hemorrhage was high in the population studied, especially the severe form. Perinatal and neonatal risk factors were associated with a higher risk of developing the disease and the outcomes studied were more evident in these newborns.

Necrostatin-1 decreases necroptosis and inflammatory markers after intraventricular hemorrhage in mice

Necrostatin-1,an inhibitor of necroptosis,can effectively inhibit necrotic apoptosis in neurological diseases,which results in the inhibition of inflammation,endoplasmic reticulum stress,and reactive oxygen species production and substantial improvement of neurological function.However,the effects of necrostatin-1 on intraventricular hemorrhage(IVH)remain unknown.In this study,we established a mouse model of IVH by injecting autologous blood into the lateral ventricle of the brain.We also injected necrostatin-1 into the lateral ventricle one hour prior to IVH induction.We found that necrostatin-1 effectively reduced the expression levels of the necroptosis markers receptor-interacting protein kinase(RIP)1,RIP3,mixed lineage kinase domain-like protein(MLKL),phosphorylated(p)-RIP3,and p-MLKL and the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-αin the surrounding areas of the lateral ventricle.However,necrostatin-1 did not reduce ependymal ciliary injury or brain water content.These findings suggest that necrostatin-1 can prevent local inflammation and microglial activation induced by IVH but does not greatly improve prognosis.

Is External Ventricular Drainage Life-Saving in Cerebellar Hemorrhages?

Background: The treatment of cerebellar hemorrhage (CH) may be different surgery or conservative according to the hematoma volume, compression of vital structures or hydrocephalus existence. In the present study, the authors investigated the risk factors, the indications and the situation of external ventricular drainage (EVD) on the treatment line. Methods: 63 pure cerebellar hemorrhage patients were enrolled in the study. 36 cases underwent surgery;the other 27 were received conservative treatment. 15 and 13 cases received EVD in both groups. Hospital stay and mortality rates were investigated. Results: 4 cases in the conservative group underwent surgery secondary to treatment failure. Both of the groups had equal rates of morbidity and mortality. On the other hand, the group that received surgical intervention had shorter median hospital stay. The EVD does not seem to be life-saving at first but it gives time for preparing for surgery. Conclusions: We found that CH was strongly associated with early hydrocephalus and mortality. The early diagnosis and surgical evacuation of the mass are mandatory and life-saving if hematoma is larger than 10 ml. The EVD may not being a life-saving instrument but majorly it may be a time earning device if acute hydrocephalus present.

Selective verbal memory impairment due to left fornical crus injury in a patient with intraventricular hemorrhage

The fornix, a part of the Papez circuit, transfers information of episodic memory between the medial temporal lobe and the medial diencephalon （Aggleton and Brown, 1999）. The right medial temporal lobe is known to be specialized for visual memory and the left medial temporal lobe for verbal memory （Tucker et al., 1988; Aegleton and Brown, 1999）.

Influence of deferoxamine on hydrocephalus after intraventricular hemorrhage and expressions of Wnt1 and Wnt3a in rat

Objective To observe the effect of deferoxamine on chronic hydrocephalus after intraventricular hemorrhage (IVH) and the role of Wnt (Wnt1 and Wnt3a) . Methods A total of 130 Sprague Dawley male rats were randomly assigned into 4 groups: normal control group, sham IVH group,IVH group and deferoxamine-treated group.

TUG-891 inhibits neuronal endoplasmic reticulum stress and pyroptosis activation and protects neurons in a mouse model of intraventricular hemorrhage

Pyroptosis plays an important role in hemorrhagic stroke.Excessive endoplasmic reticulum stress can cause endoplasmic reticulum dysfunction and cellular pyroptosis by regulating the nucleotide-binding oligomerization domain and leucine-rich repeat pyrin domain-containing protein 3(NLRP3)pathway.However,the relationship between pyroptosis and endoplasmic reticulum stress after intraventricular hemorrhage is unclear.In this study,we established a mouse model of intraventricular hemorrhage and found pyroptosis and endoplasmic reticulum stress in brain tissue.Intraperitoneal injection of the selective GPR120 agonist TUG-891 inhibited endoplasmic reticulum stress,pyroptosis,and inflammation and protected neurons.The neuroprotective effect of TUG-891 appears related to inhibition of endoplasmic reticulum stress and pyroptosis activation.

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.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

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.