Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Comparative strategies for stem cell biodistribution in a preclinical study.

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30-Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial Atherosclerotic Stenosis Stenting.

BACKGROUND: In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting. METHODS: We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses. RESULTS: The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023). CONCLUSIONS: Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting.

New evidence on the real role of digital economy in influencing public health efficiency.

In recent years, the rapid advancement of digital technology has supported the growth of the digital economy. The transformation towards digitization in the public health sector serves as a key indicator of this economic shift. Understanding how the digital economy continuously improves the efficiency of public health services and its various pathways of influence has become increasingly important. It is essential to clarify the impact mechanism of the digital economy on public health services to optimize health expenditures and advance digital economic construction. This study investigates the impact of digital economic development on the efficiency of public health services from a novel perspective, considering social media usage and urban-rural healthcare disparities while constructing a comprehensive index of digital economic development. The findings indicate that the digital economy reduces the efficiency of public health services primarily through two transmission mechanisms: the promotion of social media usage and the widening urban-rural healthcare gap. Moreover, these impacts and transmission pathways exhibit spatial heterogeneity. This study unveils the intrinsic connection and mechanisms of interaction between digital economic development and the efficiency of public health services, providing a theoretical basis and reference for government policy formulation. However, it also prompts further considerations on achieving synergy and interaction between the digital economy and public health services.

Efficacy of levetiracetam combined with oxcarbazepine in the treatment of adults with temporal lobe epilepsy and its impact on memory and cognitive function.

OBJECTIVE: To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy. METHODS: This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed. RESULTS: CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy. CONCLUSION: Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.

Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway.

Both therapeutic hypothermia and neural stem cells (NSCs) transplantation have shown promise in neuroprotection and neural repair after brain injury. However, the effects of therapeutic hypothermia on neuronal differentiation of NSCs are not elucidated. In this study, we aimed to investigate whether mild hypothermia promoted neuronal differentiation in cultured and transplanted human NSCs (hNSCs). A significant increase in neuronal differentiation rate of hNSCs was found when exposed to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo. Additionally, single-cell RNA sequencing identified upregulation of RNA-binding motif protein 3 (RBM3) in neuroblast at 35°C, which stabilized the SRY-box transcription factor 11 (SOX11) mRNA and increased its protein expression, leading to an increase in neuronal differentiation of hNSCs. In conclusion, our study highlights that mild hypothermia at 35°C enhances hNSCs-induced neurogenesis through the novel RBM3-SOX11 signaling pathway, and provides a potential treatment strategy in brain disorders.

Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.

Towards sustainability: the impact of industrial synergistic agglomeration on the efficiency of regional green development.

Guided by the concept related to sustainable development, we investigate the effects related to the synergistic agglomeration development of productive service and manufacturing industries on regional green development, which is also an important path for promoting the global sustainable development process and achieving carbon neutrality goals. Using the panel data of 285 prefecture-level cities in China from 2011 to 2020 as the basis of our study, we focus on the impact of industrial synergistic agglomeration on the efficiency of regional green development and the mediating influence of technological innovation. Results show that (1) industrial synergistic agglomeration positively contributes to the improvement of regional green development efficiency level and is significantly positive at the 5% level, (2) technological innovation plays a mediating role in the process of promoting regional green development efficiency through industrial synergistic agglomeration and can better realise the green development effect of industrial synergistic agglomeration, (3) results of the threshold effect test show the nonlinear effect of industrial synergistic agglomeration on regional green development efficiency with a single threshold value of 3.2397, and (4) the effect of industrial synergistic agglomeration on regional green development efficiency shows significant variability under different geographical locations, city scales, and resource endowment conditions. On the basis of these findings, we propose corresponding policy recommendations for improving the quality of inter-regional industrial synergistic agglomeration and formulating differentiated policy guidelines to help regions achieve long-term sustainable development.

Effect of Sasobit/Waste Cooking Oil Composite on the Physical, Rheological, and Aging Properties of Styrene-Butadiene Rubber (SBR)-Modified Bitumen Binders.

The modifying effects of polymer on bitumen low-temperature performance are substantially compromised by the thermal breakdown of styrene-butadiene rubber (SBR) polymer during bitumen mixture production operations. The efficacy of the utilization of Sasobit/waste cooking oil (Sasobit/WCO) as a warm-mix additive has been demonstrated in mitigating the adverse consequences of thermal aging on SBR-modified bitumen binder (SB) while preserving the binder's original performance characteristics. However, few studies have been conducted to further investigate the rheological properties and aging resistance of SB modified with Sasobit/WCO compounds. In this work, three additives-Sasobit, WCO, and Sasobit/WCO composite-were selected, and their effects on the physical and rheological characteristics of SB as well as the temperatures at which the mixtures were prepared were assessed. In addition, by using dynamic shear rheometers (DSR) and bending beam rheometers (BBR), the effects of this innovative warm-mix addition on the performance grade (PG) and aging resistances of SB were evaluated. According to the results, Sasobit/WCO composites outperform Sasobit and WCO in lowering the mixture preparation temperature. Sasobit/WCO also improves both the high- and low-temperature performance of SB simultaneously. Compared to hot-mix asphalt mixtures, the addition of Sasobit/WCO reduces the preparation temperature of the bitumen mixtures by 19 °C, which in turn helps to minimize the negative effects of temperature aging on the functioning of the SB. Additionally, the Sasobit/WCO composite addition can improve the SB mixture's resistance to thermal cracking. After the introduction of Sasobit/WCO, the high-temperature PG of SB was raised by two levels, regardless of whether the warm-mix impact was taken into account. With the addition of Sasobit/WCO, SB's resilience to short-term aging was enhanced.

Green credit and enterprise green operation: Based on the perspective of enterprise green transformation.

This paper uses panel data of listed heavily polluting enterprises from 2007 to 2021, based on the perspective of transformation and upgrading of heavy polluters, innovatively studies the impact of green credit on the green operation of enterprises. At the micro level, the research results of this paper verify the effectiveness of green credit policy on the transformation of green enterprises. It is also found that the two intermediary paths of debt cost and government subsidy play a partial intermediary role in the process of green credit promoting green enterprise transformation and upgrading. Green credit policy also moderates the green transformation of enterprises through debt cost and government subsidies. Based on the research results, this paper puts forward targeted policy suggestions from the aspects of financing constraints, government subsidy policies, enterprise technological innovation and green operation, and provides empirical support for the current expansion of green credit policies in China.

JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated, among them JKAP and Th17 cells relate to cognitive impairment progression in Alzheimer's disease patients.

BACKGROUND: JNK pathway-associated phosphatase (JKAP) is engaged in Alzheimer's disease (AD) pathology via regulating immune response, cluster of differentiation 4 positive (CD4+) T cell differentiation, inflammation, and phosphorylated tau (p-tau). This study aimed to investigate its clinical value serving as a biomarker for AD. METHODS: Fifty AD patients, 50 Parkinson's disease (PD) patients, and 50 controls (patients with non-degenerative neurological diseases with normal cognition) were enrolled. Their ß-protein 42 (Aß42), total tau (t-tau), p-tau, and Mini-Mental State Examination (MMSE) scale were assessed. Furthermore, JKAP in serum and T-help type 1 (Th1) and T-help type 17 (Th17) cells in CD4+ T cells were measured. RESULTS: JKAP level was lower, while Th17 cell proportion (but not Th1 cell proportion) was higher in AD patients compared with PD patients and controls (all P < 0.01). Besides, JKAP level negatively correlated with both Th1 (r = - 0.306, P = 0.030) and Th17 (r = - 0.380, P = 0.006) cell proportions in AD patients but not PD patients and controls. Furthermore, in AD patients, JKAP positively correlated with Aß42 (r = 0.307, P = 0.030) and MMSE score (r = 0.350, P = 0.013) while negatively correlated with p-tau (r = - 0.280, P = 0.048); Th17 cell proportion negatively associated with Aß42 (r = - 0.281, P = 0.048) and MMSE score (r = - 0.366, P = 0.009). Notably, JKAP was negatively related to 1-year (r = - 0.297, P = 0.038) and 2-year MMSE decline (r = - 0.304, P = 0.048); Th17 cell proportion was positively linked with 1-year (r = 0.392; P = 0.008), 2-year (r = 0.482, P = 0.001), and 3-year (r = 0.365, P = 0.013) MMSE decline. CONCLUSION: JKAP, Th1 cells, and Th17 cells are dysregulated and inter-correlated; among them, JKAP and Th17 cells relate to cognitive impairment progression in AD patients.

A near-infrared dicyanoisophorone-based fluorescent probe for discriminating HSA from BSA.

Despite the rapid development of fluorescent probe techniques for the detection of human serum albumin (HSA), a probe that discriminates between HSA and bovine serum albumin (BSA) is still a challenging task, since their similar chemical structures. As a continuation of our work, herein, a dicyanoisophorone-based fluorescent probe DCO2 is systematically studied for discrimination of HSA from BSA. The photophysical and sensing performances of DCO2, including basic spectroscopic properties, sensing sensitivity, and selectivity, exhibits that DCO2 could selectively bind with HSA and display remarkable fluorescence enhancement (∼254-fold) at 685 nm. The gap of the fluorescent response of DCO2 between HSA and BSA is an obvious increase from 21% to 73% compared to the previous probe DCO1. The sensing mechanism was elucidated by Job's plot, displacement experiment, and molecular docking, suggesting that the specific response to HSA originated from the rigid donor structure and steric hindrance. DCO2 could be buried in the DS1 pocket of HSA, and only partly wedged into the DS1 pocket of BSA with exposing twisted N,N-diethylamino group outside. Application studies indicated that DCO2 has well detective behavior for HSA in the biological fluids. This work could provide a new approach to design HSA-specific near-infrared fluorescence probes.

A surfactant-assisted approach enables the fluorescence tracking of benfluralin in plants.

Developing an effective detection method for benfluralin (BFA) is of great significance, since BFA as most widely used herbicides can be bioaccumulated by aquatic organisms in environment, possessing potential risks to human health. Owing to aggregation-caused quenching effect, most fluorescent detection methods based on donor-acceptor organic fluorophores suffered from very low sensitivity towards BFA in water system, hampering the bioimaging application in plants. In this work, we reported a novel surfactant-assisted fluorescent probe enabling detection of BFA in water with a high sensitivity. The involvement of specific surfactant Triton X100 (TX100) could amplify the response signal of probe more than 100-fold. The detection limit for BFA was determined to be 80 nM, satisfying the environmental protection requirements. Moreover, we demonstrated applications of this strategy for the fluorescent imaging of BFA in plant. The absorbance of BFA into roots of Arabidopsis thaliana and castor seedlings was successfully observed based on this method.

Modulating donor of dicyanoisophorone-based fluorophores to detect human serum albumin with NIR fluorescence.

It is urgently needed to develop NIR-fluorescent probe for detection of human serum albumin (HSA) since the interference of short-wavelength-fluorescence from endogenous species in real serum and urine. However, most previous reports were located in the short-wavelength region (<600 nm). In this work, a series of dicyanoisophorone (DCO)-based fluorophores 1-4 with different donor groups have been designed and investigated. A systematic study of their photophysical properties has been carried out. Among these probes, 4 exhibited NIR emission with the highest fluorescence brightness and the most sensitive signal response to HSA. Further studies demonstrated that 4 could strongly bind into the DS1 pocket of HSA with a 1:1 ratio. Importantly, the method based on 4 has been proven to be capable of sensing HSA in real serum and urine samples.

Fluorescence discrimination of HSA from BSA: A close look at the albumin-induced restricted intramolecular rotation of flavonoid probe.

Discrimination of human serum albumin (HSA) from bovine serum albumin (BSA) based on the fluorescence probe technique is still challenging due to similar chemical structures. In this work, a novel flavonoid-based fluorescent probe AF is reported for successful discrimination of HSA from BSA. The sensing performances of probe, including sensing dynamic, sensitivity and selectivity, have been carefully studied. Moreover, sensing mechanism was elucidated by Job's plot, displacement experiment, and molecular docking, suggesting that the specific response to HSA originated from the albumin-induced restricted intramolecular rotation (RIR) of probe. This work may provide a simple way for designing of novel probes for HSA with high selectivity.

General Method for Pesticide Recognition Using Albumin-Based Host-Guest Ensembles.

The massive use of pesticides nowadays has led to serious consequences for the environment and public health. Fluorescence analytical methods for pesticides are particularly advantageous with respect to simplicity and portability; however, currently available fluorescence methods (enzyme-based assays and indicator displacement assays) with poor universality are only able to detect few specific pesticides (e.g., organophosphorus). Making use of the multiple flexible and asymmetrical binding sites in albumin, we herein report a set of multicolor albumin-based host-guest ensembles. These ensembles exhibit a universal but distinctive fluorescent response to most of the common pesticides and allow array-based identification of pesticides with high accuracy. Furthermore, the simplicity, portability, and visualization of this method enable on-site determination of pesticides in a practical setting. This albumin host strategy largely expands the toolbox of traditional indicator displacement assays (synthetic macrocycles as hosts), and we expect it to inspire a series of sensor designs for pesticide detection.

Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy.

BACKGROUND: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. METHODS: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. RESULTS: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. CONCLUSIONS: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.

A retrospective study on the preventive effect of statin after carotid artery stenting.

ABSTRACT: This retrospective study appraised the preventive effect of statin after carotid artery stenting (CAS).Records were extracted for 100 patients with CAS surgery indicator, aged between 20 and 75 years old, and treated for statin. The cohort study included treatment group (statin and routine treatment) and control group (routine treatment), each group 50 patients. Outcomes consisted of degree of nerve defect (as measured by National Institute of Health Stroke Scale), lipid profiles (mg/dL), and CAS complications within 30 days after surgery.After treatment, there were no significant differences in National Institute of Health Stroke Scale, lipid profiles, and mortality rate between 2 groups. However, significant differences in total cholesterol (mg/dL, P = .03), low-density lipoprotein (mg/dL, P = .01), transient ischemic attack (P = .03), ischemic stroke (P = .04), and cardiac complications (P = .03) were identified within 30 days after CAS between 2 groups.The results of this study showed that prior statin treatment may be effective for the prevention of CAS complications.

Can respiratory muscle training therapy effectively manage obstructive sleep apnea syndrome after stroke?: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will explore the effectiveness and safety of respiratory muscle training therapy (RMTT) for the treatment of patients with obstructive sleep apnea syndrome (OSAS) after stroke. METHODS: In this study, we will systematically and comprehensively search Cochrane Library, PubMed, EMBASE, WANGFANG, VIP, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure for relevant literature from their inception to March 1, 2020 without any limitations to language and publication status. We will consider any randomized controlled trials focusing on the effectiveness and safety of RMTT for the treatment of patients with OSAS after stroke. The study quality will be checked using Cochrane risk of bias tool, and statistical analysis will be performed utilizing RevMan 5.3 software. RESULTS: This study will summarize and synthesize the current evidence of RMTT for the treatment of patients with OSAS following stroke. CONCLUSION: The findings of this study will assess the present evidence for the benefits and harms of RMTT for treating OSAS after stroke, and will inform clinical practice and future research. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020170355.

The neurovascular protective effect of alogliptin in murine MCAO model and brain endothelial cells.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.