Dynamic RGD ligands derived from highly mobile cyclodextrins regulate spreading and proliferation of endothelial cells to promote vasculogenesis.

A thiolated RGD was incorporated into the threaded allyl-ß-cyclodextrins (Allyl-ß-CDs) of the polyrotaxane (PR) through a thiol-ene click reaction, resulting in the formation of dynamic RGD ligands on the PR surface (dRGD-PR). When maintaining consistent RGD density and other physical properties, endothelial cells (ECs) cultured on dRGD-PR exhibited significantly increased cell proliferation and a larger cell spreading area compared to those on the non-dynamic RGD (nRGD-PCL). Furthermore, ECs on dRGD-PR demonstrated elevated expression levels of FAK, p-FAK, and p-AKT, along with a larger population of cells in the G2/M stage during cell cycle analysis, in contrast to cells on nRGD-PCL. These findings suggest that the movement of the RGD ligands may exert additional beneficial effects in promoting EC spreading and proliferation, beyond their essential adhesion and proliferation-promoting capabilities, possibly mediated by the RGD-integrin-FAK-AKT pathway. Moreover, in vitro vasculogenesis tests were conducted using two methods, revealing that ECs cultured on dRGD-PR exhibited much better vasculogenesis than nRGD-PCL in vitro. In vivo testing further demonstrated an increased presence of CD31-positive tissues on dRGD-PR. In conclusion, the enhanced EC spreading and proliferation resulting from the dynamic RGD ligands may contribute to improved in vitro vasculogenesis and in vivo vascularization.

Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health.

Due to the increased crewed spaceflights in recent years, it is vital to understand how the space environment affects human health. A lack of gravitational force is known to risk multiple physiological functions of astronauts, particularly damage to the central nervous system (CNS). As innate immune cells of the CNS, microglia can transition from a quiescent state to a pathological state, releasing pro-inflammatory cytokines that contribute to neuroinflammation. There are reports indicating that microglia can be activated by simulating microgravity or exposure to galactic cosmic rays (GCR). Consequently, microglia may play a role in the development of neuroinflammation during spaceflight. Prolonged spaceflight sessions raise concerns about the chronic activation of microglia, which could give rise to various neurological disorders, posing concealed risks to the neural health of astronauts. This review summarizes the risks associated with neural health owing to microglial activation and explores the stressors that trigger microglial activation in the space environment. These stressors include GCR, microgravity, and exposure to isolation and stress. Of particular focus is the activation of microglia under microgravity conditions, along with the proposal of a potential mechanism.

Nanoarchitectonics of tannic acid based injectable hydrogel regulate the microglial phenotype to enhance neuroplasticity for poststroke rehabilitation.

BACKGROUND: Stroke is the second leading cause of mortality and disability worldwide. Poststroke rehabilitation is still unsatisfactory in clinics, which brings great pain and economic burdens to stroke patients. In this study, an injectable hydrogel in which tannic acid (TA) acts as not only a building block but also a therapeutic drug, was developed for poststroke rehabilitation. METHODS: TA is used as a building block to form an injectable hydrogel (TA gel) with carboxymethyl chitosan (CMCS) by multivalent hydrogen bonds. The morphology, rheological properties, and TA release behavior of the hydrogel were characterized. The abilities of the TA gel to modulate microglial (BV2 cells) polarization and subsequently enhance the neuroplasticity of neuro cells (N2a cells) were assessed in vitro. The TA gel was injected into the cavity of stroke mice to evaluate motor function recovery, microglial polarization, and neuroplasticity in vivo. The molecular pathway through which TA modulates microglial polarization was also explored both in vitro and in vivo. RESULTS: The TA gel exhibited sustainable release behavior of TA. The TA gel can suppress the expression of CD16 and IL-1ß, and upregulate the expression of CD206 and TGF-ß in oxygen and glucose-deprived (OGD) BV2 cells, indicating the regulation of OGD BV2 cells to an anti-inflammatory phenotype in vitro. This finding further shows that the decrease in synaptophysin and PSD95 in OGD N2a cells is effectively recovered by anti-inflammatory BV2 cells. Furthermore, the TA gel decreased CD16/iNOS expression and increased CD206 expression in the peri-infarct area of stroke mice, implying anti-inflammatory polarization of microglia in vivo. The colocalization of PSD95 and Vglut1 stains, as well as Golgi staining, showed the enhancement of neuroplasticity by the TA gel. Spontaneously, the TA gel successfully recovered the motor function of stroke mice. The western blot results in vitro and in vivo suggested that the TA gel regulated microglial polarization via the NF-κB pathway. CONCLUSION: The TA gel serves as an effective brain injectable implant to treat stroke and shows promising potential to promote poststroke rehabilitation in the clinic.

Catalytic combustion of lean methane over different Co3O4 nanoparticle catalysts.

Three types of Co3O4 catalyst, namely Co3O4 nanoparticles (denoted as Co3O4-NPs, ∼12 nm in diameter), Co3O4 nanoparticles encapsulated in mesoporou s SiO2 (denoted as Co3O4@SiO2), and Co3O4 nanoparticles inside microporous SiO2 hollow sub-microspheres (denoted as Co3O4-in-SiO2), were explored to catalyze the combustion of lean methane. It was found that the methane conversion over the three catalysts has the order of Co3O4-NPs ≈ Co3O4@SiO2 > Co3O4-in-SiO2 due to the different catalyst structure. The comparison experiments at high temperatures indicate the Co3O4@SiO2 has a significantly improved anti-sintering performance. Combined with the TEM and BET measurements, the results prove that the presence of the mesoporous SiO2 layer can maintain the catalytical activity and significantly improve the anti-sintering performance of Co3O4@SiO2. In contrast, the microporous SiO2 layer reduces the catalytical activity of Co3O4-in-SiO2 possibly due to its less effective diffusion path of combustion product. Thus, the paper demonstrates the pore size of SiO2 layer and catalyst structure are both crucial for the catalytical activity and stability.

Meta-analysis of repetitive transcranial magnetic stimulation combined with task-oriented training on upper limb function in stroke patients with hemiplegia.

BACKGROUND: To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) combined with task-oriented training (TOT) on upper limb function in stroke patients with hemiplegia. METHODS: A systematic review and meta-analysis was performed using PRISMA guidelines. Computer searches of PubMed, Cochrane Library, Embase, Web of science, China Knowledge Network, Wanfang, and Wipu databases were conducted from the time of database creation to October 27, 2022. Clinical trials meeting the inclusion criteria were screened, with rTMS combined with TOT in the test group and other therapies in the control group. Literature screening and data extraction were performed independently by 2 investigators, and meta-analysis was performed using Stata software after quality evaluation of the literature. RESULTS: Meta-analysis results showed that repeated transcranial magnetic stimulation combined with TOT was more effective in box and block test (I2 = 0%, P = .820, 95% confidence interval [CI] [-0.20, 0.88]), Fugl-Meyer Assessment (I2 = 0%, P = .569, 95% CI [0.88, 1.26]), and modified Barthel Index (I2 = 39.9%, P = .189, 95% CI [0.45, 1.03]) were not significantly different from controls, and the efficacy was significantly better in motor evoked potentials (I2 = 86.5%, P < .001, 95% CI [-1.38, -0.83]). CONCLUSIONS: Data analysis clarified the efficacy of rTMS) combined with TOT on upper extremity motor function disorders after stroke, but there was no significant difference between the efficacy in box and block test, Fugl-Meyer Assessment, and modified Barthel Index and the efficacy in motor evoked potentials between rTMS and the control group, suggesting that the neuro plasticizing effect of rTMS may translate into functional improvement by promoting neuro electrical signaling.

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.

Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage of pathological development. Neuroprotection is the main treatment in the acute phase, and functional recovery becomes primary in the subacute and chronic phases. Neuroplasticity is considered the basis of functional restoration and neurological rehabilitation after stroke, including the remodeling of dendrites and dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, and neurogenesis. Spatiotemporal development affects the spontaneous rewiring of neural circuits and brain networks. Microglia are resident immune cells in the brain that contribute to homeostasis under physiological conditions. Microglia are activated immediately after stroke, and phenotypic polarization changes and phagocytic function are crucial for regulating focal and global brain inflammation and neurological recovery. We have previously shown that the development of neuroplasticity is spatiotemporally consistent with microglial activation, suggesting that microglia may have a profound impact on neuroplasticity after stroke and may be a key therapeutic target for post-stroke rehabilitation. In this review, we explore the impact of neuroplasticity on post-stroke restoration as well as the functions and mechanisms of microglial activation, polarization, and phagocytosis. This is followed by a summary of microglia-targeted rehabilitative interventions that influence neuroplasticity and promote stroke recovery.

Exploring the relationship between intestinal flora and the pathological mechanism of myopia in adolescents from the perspective of Chinese and Western medicine: A review.

The etiology of adolescent myopia involves genetic and environmental factors. The pathological mechanism of modern medicine includes blood perfusion, changes in blood molecules, neurotransmitters, and sclera remodeling. Chinese medicine believes that myopia is mainly related to the deficiency of liver blood and spleen and stomach disorders. The prevention and treatment of myopia in adolescents are very important, but in terms of the current incidence of myopia in adolescents and the level of clinical diagnosis and treatment, its prevention and treatment are insufficient. Modern medicine and traditional Chinese medicine both pay attention to integrity, so adolescent myopia should not only pay attention to eye changes but also pay attention to other body systems and other aspects of change. Intestinal flora has become a research hotspot in recent years, and it has been found that it is closely associated with multi-system and multi-type diseases. No studies have directly investigated the link between Intestinal flora and myopia in adolescents. Therefore, by summarizing the pathological mechanism of adolescent myopia and the connection between intestinal flora and the pathological mechanism of adolescent myopia, this paper analyzes the possible pathological mechanism of the influence of intestinal flora on adolescent myopia, providing a theoretical basis for future studies on the correlation between changes of intestinal flora and its metabolites and the incidence of adolescent myopia, which is of great significance for the study on the risk prediction of adolescent myopia.

Expression profile of circular RNAs in patients with unstable angina.

BACKGROUND: Circular RNAs (circRNAs) are a new class of noncoding RNAs, which interfere with gene transcription by absorbing microRNAs (miRNAs). OBJECTIVE: The expression profile and roles of circRNAs in unstable angina (UA) patients remains unclear. METHODS: An initial screening of circRNA expression by microarray analysis was performed using blood samples from three pairs of UA patients and matched healthy individuals. The differential expression of the chosen six circRNAs from the results of the microarray analysis was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The microarray results demonstrated that some circRNAs were markedly different in UA patients, when compared with matched healthy individuals. In these UA patients, 22 circRNAs were upregulated and six circRNAs were downregulated when a P-value of < 0.05 was considered as a cut-off level and the fold change was > 1.5. Among the six circRNAs chosen for further analysis, qRT-PCR identified that five of these were upregulated, and the remaining circRNA was downregulated. By comparing the outcome of the six candidate circRNAs between the circRNAs microarray assay and RT-PCR validation, it was found that four circRNAs (hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667, and hsa_circ_0001451) had the same variation trend. CONCLUSION: The present study provided the expression profile of circRNAs in UA patients. Moreover, some circRNAs have the potential to be biomarkers for the detection of UA patients. Further studies with a larger population will focus on hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667 and hsa_circ_0001451.

Immunocytes Rapid Responses Post-ischemic Stroke in Peripheral Blood in Patients With Different Ages.

Objectives: To explore the alterations in immune cell composition in peripheral blood in patients with acute ischemic stroke (AIS) based on their age group. Methods: Patients with imaging confirmed AIS were enrolled from April 2019 to January 2020 and were divided into three groups according to their ages: <55 years (group-A), 55-65 years (group-B), and >65 years (group-C). Blood samples were collected immediately when the patients were admitted to our ward prior to any intervention. Flow cytometry was used to analyze immune cell composition in peripheral blood. Results: A total of 41 eligible patients were included for final analysis. Among the three groups, the proportions of CD56+ CD16dim NK cells were least to greatest in group-B, group-A, then group-C, respectively. With increasing age, there was a decrease in the proportion of CD3+ T-cells (group-A vs. group-C, P = 0.016) and CD3+CD4+ T-cells (group-C vs. group-A, P = 0.008; group-C vs. group-B P = 0.026). Meanwhile, no significant differences in proportions of monocytes and B cells were observed. Conclusions: The compositions of immune cells in peripheral blood of AIS patients were distinct when divided by age groups. Differences in immune cell ratios may affect clinical outcomes and foreshadows possible need for customized treatment of AIS in different age groups.

Hydrogen Evolution from Additive-Free Formic Acid Dehydrogenation Using Weakly Basic Resin-Supported Pd Catalyst.

Hydrogen, as a noncarbon energy source, plays a significant role in future clean energy vectors. However, concerns about the safe storage and transportation of hydrogen gas limit its wide application. Featured with high H2 volumetric density, nontoxicity, and nonflammability, formic acid (FA) is regarded as one of the most encouraging chemical hydrogen carriers. The search for heterogeneous catalysts with decent catalytic activity and stability for FA decomposition is one of the hottest research topics in this area. In this paper, three weakly basic resins with different functional groups, including D201 with -N+(CH3)3, D301 with -N(CH3)2, and D311 with -NH2, were investigated as alternative catalyst supports for Pd catalysts. The prepared basic resin-supported Pd catalysts were evaluated for the FA dehydrogenation reaction under atmospheric pressure and temperatures ranging from 30 to 70 °C. The results showed that the catalytic activity of the three different resin-supported Pd catalysts follows the order of Pd/D201 > Pd/D301 > Pd/D311. Particularly, a high turnover frequency value of 547.6 h-1 was achieved when employing Pd/D201 as the FA dehydrogenation reaction catalyst at 50 °C. The apparent activation energies for the three different Pd/resin catalysts were calculated, of which the Pd/D210 catalyst demonstrates the lowest activation energy of 42.9 kJ mol-1. The reasons for the superior catalytic behavior, together with the reaction mechanism, were then investigated and illustrated.

Mechanism of One-Step Hydrothermally Synthesized Titanate Catalysts for Ozonation.

A titanate nanotube catalyst for ozonation was synthesized with a simple one-step NaOH hydrothermal treatment without energy-consuming calcination. The synthesized titania catalysts were characterized by X-ray diffraction (XRD), Raman, porosimetry analysis, high-resolution transmission electron microscopy (HR-TEM), Fourier transformed infrared (FTIR), and electron paramagnetic resonance (EPR) analysis. The catalyst treated with a higher concentration of NaOH was found to be more catalytically active for phenol removal due to its higher titanate content that would facilitate more OH groups on its surface. Furthermore, the main active oxidizing species of the catalytic ozonation process were recognized as singlet oxygen and superoxide radical, while the hydroxyl radical may only play a minor role. This work provides further support for the correlation between the properties of titania and catalytic performance, which is significant for understanding the mechanism of catalytic ozonation with titania-based materials.

Design and Fabrication of Polymeric Hydrogel Carrier for Nerve Repair.

Nerve regeneration and repair still remain a huge challenge for both central nervous and peripheral nervous system. Although some therapeutic substances, including neuroprotective agents, clinical drugs and stem cells, as well as various growth factors, are found to be effective to promote nerve repair, a carrier system that possesses a sustainable release behavior, in order to ensure high on-site concentration during the whole repair and regeneration process, and high bioavailability is still highly desirable. Hydrogel, as an ideal delivery system, has an excellent loading capacity and sustainable release behavior, as well as tunable physical and chemical properties to adapt to various biomedical scenarios; thus, it is thought to be a suitable carrier system for nerve repair. This paper reviews the structure and classification of hydrogels and summarizes the fabrication and processing methods that can prepare a suitable hydrogel carrier with specific physical and chemical properties. Furthermore, the modulation of the physical and chemical properties of hydrogels is also discussed in detail in order to obtain a better therapeutic effect to promote nerve repair. Finally, the future perspectives of hydrogel microsphere carriers for stroke rehabilitation are highlighted.

Anti-coagulation and anti-hyperplasia coating for retrievable vena cava filters by electrospraying and their performance in vivo.

A novel drug eluting retrievable vena cava filter (RVCF) with a heparin-modified poly(ε-caprolactone) (hPCL) coating containing rapamycin was prepared by electrospraying. The in vitro drug release pattern showed that the encapsulated rapamycin in the coating can be sustainably released within one month, whereas activated partial thromboplastin time (APTT) and in vitro cell culture showed that the drug eluting RVCF can effectively extend blood clotting time and inhibit smooth muscle cell (SMC) and endothelial cell (EC) proliferation, respectively. The as-prepared drug eluting RVCF and corresponding commercial RVCF were implanted into the vena cava of sheep. The retrieval operation at a predetermined time point showed that the drug eluting RVCF had a much higher retrieval rate than the commercial RVCF. Comprehensive investigations, including histological, immunohistological and immunofluorescence analyses, on explanted veins were carried out. The results demonstrated that the as-prepared RVCF possessed excellent antihyperplasia properties in vivo, significantly improving the retrieval rate and extending the in vivo dwelling time in sheep. Consequently, the drug eluting RVCF has promising potential for application in the clinic to improve RVCF retrieval rates.

Microbubbles intensification and mechanism of wet air oxidation process of MDEA-containing wastewater.

In order to the intensification of gas-liquid mass transfer of MDEA-containing wastewater during wet air oxidation (WAO) process, the microbubbles and millimetre bubbles were applied by fine-pore sparger (5 and 20-30 µm) and single pore sparger (6.35 mm), respectively. Effect of the superficial gas velocity on the average microbubble size, gas holdup and oxygen mass transfer coefficient (KLa) of MDEA-containing wastewater at the ambient conditions was studied. The results showed that the microbubbles (less than 1 mm) were beneficial to enhance mass transfer process and had a higher dissolved oxygen concentration during WAO process of MDEA-containing wastewater owing to higher gas holdup and larger oxygen mass transfer coefficient. The COD removal ratio was 66% at low superficial gas velocity (ug = 0.3 cm/s) in WAO process by microbubbles, while it achieved at high superficial gas velocity (ug = 3.0 cm/s) by millimetre bubbles. The critical oxygen mass transfer coefficient KLa was 0.183 min-1 of MDEA-containing wastewater by 20-30 and 5 µm fine pore sparger, which was 2∼5 times more than that of single pore sparger (<0.1 min-1). The microbubbles could improve dissolved oxygen concentration and enhance the formation of hydroxyl radical at short time with atmospheric pressure. During the WAO process, the MDEA would be converted into intermediates including formic acid, acetic acid, ammonium, nitrite and nitrate. The WAO process with microbubbles could significantly improve the gas-liquid mass transfer performance at low superficial gas velocity and greatly reduce air consumption for MDEA-containing wastewater.

Study on wet oxidation process and mechanism for ethylene spent caustic.

Ethylene spent caustic with strong alkalinity, high chemical oxygen demand (COD) and toxicity could not be directly discharged without pretreatment. In this paper, the composition of spent caustic from a petrochemical enterprise was analyzed. Effects of oxidants, reaction temperature, pressure and residence time on the removal ratio of COD in the spent caustic were investigated. The oxidation reaction mechanism of main organic sulphides in the spent caustic was discussed. Results show that COD of the ethylene spent caustic is ∼ 24.5 g/L, the main compositions are S2- and disulphides including a small amount of ketones and phenolic organics. The removal ratio of S2- in spent caustic is up to 100%, and the removal ratio of COD is over 83% at 180 °C with the pressure of 2 MPa and residence time of 15 min using oxygen as an oxidant. Taking dimethyl disulphide as an example, dimethyl disulphide with HO• firstly produces methyl thiosulphonate and methyl sulphenic acid, then further oxidized to generate methanesulphonic acid, and the C-S bonds in the methanesulphonic acid were broken to generate sulphuric acid and formic acid. So the oxidative degradation products of organic sulphides are sulphuric acid, formic acid and a small amount of acetic acid.

Construction of PARPi Resistance-related Competing Endogenous RNA Network.

Objective: Ovarian cancer is a kind of common gynecological malignancy in women. PARP inhibitors (PARPi) have been approved for ovarian cancer treatment. However, the primary and acquired resistance have limited the application of PARPi. The mechanisms remain to be elucidated. Methods: In this study, we characterized the expression profiles of mRNA and nonconding RNAs (ncRNAs) and constructed the regulatory networks based on RNA sequencing in PARPi Olaparib-induced ovarian cancer cells. Results: We found that the functions of the differentially expressed genes were enriched in "PI3K/AKT signaling pathway," "MAPK signaling pathway" and "metabolic process". The functions of DELs (cis) were enriched in "Human papillomavirus infection""tight junction" "MAPK signaling pathway". As the central regulator of ceRNAs, the differentially expressed miRNAs were enriched in "Human papillomavirus infection" "MAPK signaling pathway" "Ras signaling pathway". According to the degree of interaction, we identified 3 lncRNAs, 2 circRNAs, 7 miRNAs, and 12 mRNA as the key regulatory ceRNA axis, in which miR-320b was the important mediator. Conclusion: Here, we revealed the key regulatory lncRNA (circRNA)-miRNA-mRNA axis and their involved pathways in the PARPi resistant ovarian cancer cells. These findings provide new insights into exploring the ceRNA regulatory networks and developing new targets for PARPi resistance.

Metal Emulsion-Based Synthesis, Characterization, and Properties of Sn-Based Microsphere Phase Change Materials.

A comparative study of the metal emulsion-based synthesis of Sn-based materials in two different types of molten salts (namely LiCl-KCl-CsCl and LiNO3-NaNO3-KNO3 eutectics) is presented, and the properties of Sn, Sn-Cu and Sn-Cu-Zn microsphere phase change materials prepared in chloride salts are evaluated by differential scanning calorimetry (DSC) to understand the effect of element doping. Despite a high ultrasonic power (e.g., 600 W or above) being required for dispersing liquid Sn in the chloride system, well-shaped Sn microspheres with a relatively narrow size range, e.g., about 1 to 15 µm or several micrometers to around 30 µm, can be prepared by adjusting the ultrasonic power (840-1080 W), sonication time (5-10 min) and the volume ratio of salts to metal (25:1-200:1). Such a method can be extended to the synthesis of Sn-based alloy microspheres, e.g., Sn-Cu and Sn-Cu-Zn microspheres. In the nitrate system, however, a very low ultrasonic power (e.g., 12 W) can be used to disperse liquid Sn, and the particles obtained are much smaller. At low ultrasonic power (e.g., 12 W), the particle size is generally less than 10 or 4 µm when the sonication time reaches 2 or 5 min, and at high ultrasonic power, it is typically in the range of hundreds of nanometers to 2 µm, regardless of the change in ultrasonic power (480-1080 W), irradiation time (5-10 min), or volume ratio of salts to metal (25:1-1000:1). In addition, the appearance of a SnO phase in the products prepared under different conditions hints at the occurrence of a reaction between Sn droplets and O2 in situ generated by the ultrasound-induced decomposition of nitrates, and such an interfacial reaction is believed to be responsible for these differences observed in two different molten salt systems. A DSC study of Sn, Sn-Cu, and Sn-Cu-Zn microspheres encapsulated in SiO2 reveals that Cu (0.3-0.9 wt.%) or Cu-Zn (0.9 wt.% Cu and 0.6% Zn) doping can raise the onset freezing temperature and thus suppress the undercooling of Sn, but a broad freezing peak observed in these doped microspheres, along with a still much higher undercooling compared to those of reported Sn-Cu or Sn-Cu-Zn solders, suggests the existence of a size effect, and that a low temperature is still needed for totally releasing latent heat. Since the chloride salts can be recycled by means of the evaporation of water and are stable at high temperature, our results indicate that the LiCl-KCl-CsCl salt-based metal emulsion method might also serve as an environmentally friendly method for the synthesis of other metals and their alloy microspheres.

Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF-κB Suppression and NLRP3 Inflammasome Inhibition.

NLRP3 inflammasome-mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays a vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke-induced neuronal damage through modulating microglial polarization. However, the impact of curcumin on microglial pyroptosis remains unknown. Here, stroke was modeled in mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with curcumin (150 mg/kg) intraperitoneally immediately after reperfusion, followed by daily administrations for 7 days. Curcumin ameliorated white matter (WM) lesions and brain tissue loss 21 days poststroke and improved sensorimotor function 3, 10, and 21 days after stroke. Furthermore, curcumin significantly reduced the number of gasdermin D+ (GSDMD+) Iba1+ and caspase-1+Iba1+ microglia/macrophage 21 days after stroke. In vitro, lipopolysaccharide (LPS) with ATP treatment was used to induce pyroptosis in primary microglia. Western blot revealed a decrease in pyroptosis-related proteins, e.g., GSDMD-N, cleaved caspase-1, NLRP3, IL-1ß, and IL-18, following in vitro or in vivo curcumin treatment. Mechanistically, both in vivo and in vitro studies confirmed that curcumin inhibited the activation of the NF-κB pathway. NLRP3 knocked down by siRNA transfection markedly increased the inhibitory effects of curcumin on microglial pyroptosis and proinflammatory responses, both in vitro and in vivo. Furthermore, stereotaxic microinjection of AAV-based NLRP3 shRNA significantly improved sensorimotor function and reduced WM lesion following curcumin treatment in MCAO mice. Our study suggested that curcumin reduced stroke-induced WM damage, improved functional outcomes, and attenuated microglial pyroptosis, at least partially, through suppression of the NF-κB/NLRP3 signaling pathway, further supporting curcumin as a potential therapeutic drug for stroke.

New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery.

Stroke remains the leading cause of long-term disability worldwide with significant long-term sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by 3 to 4 weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximal to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to brain injuries. Microglial activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, and blood vessel regeneration. In this review, we focus on the crosstalk between microglial activation and endogenous neuroplasticity, with a special focus on the plastic alterations in the whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia-based extrinsic restorative interventions in promoting post-stroke recovery.