Previous studies have indicated the neuroprotective effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) on brain injury. Intracerebral hemorrhage (ICH) models were established in rats by injecting autologous blood. SENP1 expression was enhanced in neurons but decreased in astrocytes compared to that in OM-MSCs. Overexpression of SENP1 promoted the proliferation and neuronal differentiation, while inhibiting the astrocytic differentiation of OM-MSCs. Conversely, its knockdown had the opposite effect. Moreover, OM-MSCs reduced neurological dysfunction in rats after ICH, and the neuroprotective effect of OM-MSCs could be further enhanced by SENP1 overexpression. In addition, SENP1 promoted mitophagy, which might be related to SENP1-mediated OPTN deSUMOylation. Furthermore, SENP1 promoted neuronal differentiation of OM-MSCs through mitophagy mediated by OPTN. Similar to SENP1, OPTN transfection further enhanced the remission effect of OM-MSC on ICH rats. SENP1 promoted neuronal differentiation of OM-MSCs through OPTN-mediated mitophagy to improve neurological deficits in ICH rats.

Background: Neuronal cell ferroptosis following intracerebral hemorrhage (ICH) is a crucial factor contributing to the poor prognosis of ICH patients. The objective of this investigation was to investigate the molecular mechanism of IL-1β-induced mesenchymal stem cell-derived exosomes (IL-1β-Exo) in mitigating ICH injury. Methods: Exo and IL-1β-Exo were obtained and identified. Hemin was used to induce an ICH model, and an ICH mouse model was established using Collagenase. Exo and IL-1β-Exo interventions were conducted to study their impact and molecular mechanisms on neuronal ferroptosis in ICH. Results: Vesicular structure Exo and IL-1β-Exo, with an average particle size of 141.7 ± 38.8 nm and 138.8 ± 37.5 nm, respectively, showed high expression of CD63, CD9 and CD81 could be taken up by SH-SY5Y cells. These Exos reversed Hemin-induced abnormalities in neuronal cells, including elevated iron, Fe2+, ROS, MDA, 4-HNE, and decreased SOD, GSH-Px, GSH, FTH1 levels, and cell vitality. The RNA content of IL-1β-Exo was linked to its ability to reduce iron accumulation. There was an interaction between HSPA5 and GPX4. Exo and IL-1β-Exo reversed Hemin-induced downregulation of HSPA5 and GPX4 expression. Overexpression and knockdown of HSPA5 respectively potentiate or counteract the impacts of Exo and IL-1β-Exo. IL-1β-Exo was more effective than Exo. These findings were further validated in ICH mice. Moreover, both Exo and IL-1β-Exo reduced the modified neurological severity score and brain water content, as well as alleviated pathological damage in ICH mice. Conclusion: IL-1β-Exo inhibited neuronal ferroptosis in ICH through the HSPA5/GPX4 axis.

Ischemia/reperfusion (I/R) injury is a severe brain disorder with currently limited effective treatments. This study aims to explore the role of N6-methyladenosine (m6A) modification and associated regulatory factors in I/R to identify potential therapeutic targets. We utilized a middle cerebral artery occlusion (MCAO) rat model and SH-SY5Y cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to assess m6A levels and investigate the impact of METTL3 overexpression on long non-coding RNA (lncRNA) CRNDE expression. The effects of silencing lncRNA CRNDE on the interaction between YTHDC1 and ATG10 mRNA, as well as the stability of ATG10 mRNA, were evaluated. Additionally, apoptosis rates, pro-inflammatory and anti-inflammatory factor levels, ATG10 expression, and autophagic activity were analyzed to determine the effects of METTL3. The reverse effects of YTHDC1 overexpression were also examined. MCAO rats and OGD/R-treated SH-SY5Y cells exhibited reduced m6A levels. METTL3 overexpression significantly inhibited lncRNA CRNDE expression. Silencing lncRNA CRNDE mitigated OGD/R-induced apoptosis and inflammation in SH-SY5Y cells, while enhancing autophagy and stabilizing ATG10 mRNA. METTL3 overexpression decreased cell apoptosis, reduced the levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and increased IL-10 secretion. Furthermore, METTL3 overexpression upregulated ATG10 expression and promoted autophagy. Conversely, lncRNA CRNDE overexpression negated these effects. The inhibition of lncRNA CRNDE affects the interaction between YTHDC1 and ATG10 mRNA and stabilizes ATG10 mRNA, mediated by METTL3 overexpression. These findings suggest that targeting lncRNA CRNDE to reduce apoptosis, inhibit inflammation, increase ATG10 expression, and enhance autophagy could offer new therapeutic strategies for I/R injury.

目的 探讨海绵窦区硬脑膜动静脉瘘的介入治疗方法及其疗效.方法 回顾性分析2013年1月至2023年1月介入治疗的21例海绵窦区硬膜动静脉瘘的临床资料.结果 经股静脉-岩下窦途径16例,经颈外动脉入路4例,经动静脉联合入路1例;采用弹簧圈联合Onyx-18 胶栓塞17例,单纯应用弹簧圈1例,单用Onyx-18胶3例;术后即刻造影显示瘘口完全闭塞18例,次全闭塞3例.术后随访3～12个月,临床治愈17例,好转4例.15例复查造影未见瘘口复发.结论 根据海绵窦区硬脑膜动静瘘血管构筑特征,采用个体化的血管内治疗方案,可以获得满意的临床疗效.

OBJECTIVE:To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A.METHODS:Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A.RESULTS:The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells.CONCLUSION:Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.

Abstract Recently, the protective effect of exosomes on ischemia/reperfusion (I/R) injury has become a research hotspot. The purpose of this study was to explore the therapeutic potential of microglia-derived exosomes on cerebral I/R injury. BV2 cell-derived exosomes (BV2-Exo) were extracted and characterized. The cerebral I/R model was constructed in vivo and intervened by using exosomes loaded with miR-302a-3p. The oxygen and glucose deprivation (OGD) model was constructed in vitro to simulate cerebral I/R injury. The binding sites of miR-302a-3p to Keap1 were analyzed by bioinformatics prediction and confirmed by dual-luciferase reporter assay. A study of whether exosomal miR-302a-3p affected cerebral I/R injury via the Keap1/Nrf2 axis was carried out by overexpression of keap1 (oe-keap1). Experimental results in vivo showed exosomal miR-302a-3p significantly repaired the cognitive impairment and suppressed the cell death of hippocampal neurons induced by cerebral I/R injury. Besides, exosomal miR-302a-3p inhibited the expression of ferroptosis-related proteins NCOA4, PTGS2, and p53 in cerebral I/R-treated mice. Bioinformatics prediction and double-luciferase reporter assay showed that Keap1 was the direct downstream target of miR-302a-3p. Experiment results in vitro showed that oe-Keap1 reversed the therapeutic effect of exosomal miR-302a-3p on cerebral I/R injury via the Keap1/Nrf2 axis, promoting the high expression of NCOA4, PTGS2, and p53 and the increase of Fe2+, MDA and ROS levels. These results demonstrated that microglia-exosomal miR-302a-3p suppressed ferroptosis to alleviate cerebral I/R injury by inhibiting neuronal ferritinophagy via regulating the Keap1/Nrf2 axis.

Ischemic stroke causes lethal damage to the brain. Identifying key regulators of OGD/R-induced cerebral injury is important for developing novel therapies for ischemic stroke. HMC3 and SH-SY5Y cells were treated with OGD/R as an in vitro ischemic stroke model. Cell viability and apoptosis were determined via CCK-8 assay and flow cytometry. Inflammatory cytokines were examined by ELISA. Luciferase activity was measured for evaluating the interaction of XIST, miR-25-3p, and TRAF3. Bcl-2, Bax, Bad, cleaved-caspase 3, total caspase 3, and TRAF3 were detected via western blotting. HMC3 and SH-SY5Y cells showed increased XIST expression and decreased miR-25-3p expression following OGD/R. Importantly, silencing of XIST and overexpression of miR-25-3p reduced apoptosis and inflammatory response following OGD/R. Furthermore, XIST worked as a miR-25-3p sponge, and miR-25-3p targeted TRAF3 to suppress its expression. Moreover, the knockdown of TRAF3 ameliorated OGD/R-induced injury. Loss of XIST-mediated protective effects was reversed by overexpression of TRAF3. LncRNA XIST exacerbates OGD/R-induced cerebral damage via sponging miR-25-3p and enhancing TRAF3 expression.

急性基底动脉闭塞的患病率低,却伴随着高病死率及致残率.早期再通可改善患者的临床预后及降低患者病死率,然而其临床预后受到多种因素的影响,如年龄、发病机制、发病至再通时间、血管再通率、侧支循环开放程度等.作者就急性基底动脉闭塞再通治疗及临床预后影响因素的研究进展进行综述.

Background: Ischemic stroke is a very dangerous disease with high incidence, fatality and disability rate in human beings. Massive evidence has indicated that oxidative stress and inflammation are intimately correlated with progression of ischemic stroke. Additionally, LncRNAs were reported to be involved in ischemic stroke. Here, we aim to explore the effects and molecular mechanism of lncRNA OIP5-AS1 on oxidative stress and inflammation in ischemic stroke. Methods: HMC3 and SH-SY5Y cells were under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to establish cell models of ischemic stroke. Commercial kits were employed to detect the indicators of oxidative stress including ROS, MDA and SOD. The expression of OIP5-AS1, miR-155-5p and IRF2BP2 mRNA was determined using RT-qPCR. The protein levels of inflammatory factors including TNF-α, IL-1β and IL-6 and IRF2BP2 were assessed by western blot and/or ELISA. Luciferase activity assay was employed to validate their correlations among OIP5-AS1, miR-155-5p and IRF2BP2. Results: In OGD/R-induced HMC3 and SH-SY5Y cells, the expression of OIP5-AS1 and IRF2BP2 was reduced while miR-155-5p was elevated. OGD/R induction promoted oxidative stress and inflammatory response in HMC3 and SH-SY5Y cells, while OIP5-AS1 or IRF2BP2 sufficiency as well as miR-155-5p inhibitor attenuated OGD/R-induced these influences. In addition, IRF2BP2 knockdown abolished the suppressive impacts of OIP5-AS1 overexpression on oxidative stress and inflammatory response in OGD/R-induced HMC3 and SH-SY5Y cells. Mechanistically, OIP5-AS1 enhanced IRF2BP2 expression via sponging miR-155-5p. Conclusion: OIP5-AS1 suppressed oxidative stress and inflammatory response to alleviate cell injury caused by OGD/R induction in HMC3 and SH-SY5Y cells through regulating miR-155-5p/IRF2BP2 axis, which might offer novel targeted molecules for ischemic stroke therapy.

Objective:To explore the clinical efficacy of controlled decompression in the treatment of severe traumatic brain injury (sTBI).Methods:Thirty five patients with sTBI treated by applying controlled decompression surgery from September 2018 to September 2021 in Neurosurgery Department of Haikou Affiliated Hospital of Central South University Xiangya School of Medicine were enrolled into controlled decompression group, another 35 patients with sTBI treated by routine conventional decompression surgery from January 2015 to January 2018 were enrolled into conventional decompression group. The clinical data, complication, length of hospital stay, hospital costs and follow-up results of all cases were analyzed.Results:The surgical time of patients in the controlled decompression group was longer than that in the conventional decompression group, and the proportion of malignant encephalocele was significantly lower than that in the conventional decompression group, with statistical significance (P>0.05). The incidence, hospitalization time, and cost of postoperative complications (hydrocephalus and encephalocele) in the controlled decompression group were significantly lower than those in the conventional decompression group, and the differences were statistically significant (P>0.05). Following up for 6 months, 27 patients in the controlled decompression group achieved good results, 3 patients had severe disability, 3 patients had vegetative survival status, and 2 patients died of postoperative diffuse brain swelling. Among the 35 patients patients in the conventional decompression group, 18 were effective, 8 were severely disabled, 4 were in vegetative state, and 5 died. There was a statistically significant difference in prognosis between the two groups (P<0.05).Conclusion:Controlled decompression has a good effective in the treatment of patients with sTBI and could improve the prognosis of some patients.

Abstract Objective: Recently, the protective effect of exosomes on ischemia/reperfusion (I/R) injury has become a research hotspot. The purpose of this study was to explore the therapeutic potential of microglia-derived exosomes on cerebral I/R injury. Methods: BV2 cell-derived exosomes (BV2-Exo) were extracted and characterized. The cerebral I/R model was constructed in vivo and intervened by using exosomes loaded with miR-302a-3p. The oxygen and glucose deprivation (OGD) model was constructed in vitro to simulate cerebral I/R injury. The binding sites of miR-302a-3p to Keap1 were analyzed by bioinformatics prediction and confirmed by dual-luciferase reporter assay. A study of whether exosomal miR-302a-3p affected cerebral I/R injury via the Keap1/Nrf2 axis was carried out by overexpression of keap1 (oe-keap1). Results: Experimental results in vivo showed exosomal miR-302a-3p significantly repaired the cognitive impairment and suppressed the apoptosis of hippocampal neurons induced by cerebral I/R injury. Besides, exosomal miR-302a-3p inhibited the expression of ferroptosis-related proteins NCOA4, PTGS2, and p53 in cerebral I/R-treated mice. Bioinformatics prediction and double-luciferase reporter assay showed that Keap1 was the direct downstream target of miR-302a-3p. Experiment results in vitro showed that oe-Keap1 reversed the therapeutic effect of exosomal miR-302a-3p on cerebral I/R injury via the Keap1/Nrf2 axis, promoting the high expression of NCOA4, PTGS2, and p53 and the increase of Fe2+, MDA and ROS levels. Conclusion: The results demonstrated that microglia-exosomal miR-302a-3p suppressed ferroptosis to alleviate cerebral I/R injury by inhibiting neuronal ferritinophagy via regulating the Keap1/Nrf2 axis.