The discovery of the glymphatic system and of meningeal lymphatic vessels has substantially revised our understanding of how the central nervous system clears waste and maintains neuroimmune homeostasis. Acting in series, these two pathways remove interstitial solutes, metabolic by-products, and neurotoxic proteins such as tau and amyloid-β from the brain parenchyma and deliver them to the peripheral lymphatic system. Converging experimental and clinical evidence indicates that both pathways decline with age, and that impaired clearance contributes to the onset and progression of Alzheimer's disease, Parkinson's disease, and stroke, although the direction of causality in these associations is not yet fully resolved. In this review, we summarize current knowledge of the anatomy and physiology of the glymphatic and meningeal lymphatic systems; examine the molecular and cellular mechanisms by which their function deteriorates with age; appraise the imaging modalities and fluid biomarkers used to assess them; and evaluate the therapeutic strategies being developed to restore them. A clearer understanding of this clearance pathways may open new avenues for the treatment of age-related neurodegenerative disease.

The glymphatic system is a critical waste clearance system in the brain, playing an essential role in maintaining homeostasis within the central nervous system. Aquaporin 4 (AQP4), an indispensable component of the glymphatic system, is vital for ensuring the proper function of this system. Melatonin has been proven to be protective in treating hypoxic-ischemic encephalopathy (HIE). The aim of this study was to examine if alterations occur in the glymphatic system function in the brain of HIE model rats, and to determine whether melatonin can enhance the function of the glymphatic system by regulating AQP4, along with elucidating the mechanisms underlying melatonin's effects on AQP4. 10-day-old rat pups were subjected to hypoxic-ischemic (HI) injury; melatonin and roscovitine (an inhibitor of cyclin-dependent kinase 5) were injected intraperitoneally at 10 min following HI induction. At 24 h post-HI, intracisternal tracer infusion, neurobehavioral tests, immunofluorescence staining, western blot analysis, Evans blue (EB) permeability assay, brain water content test, ELISA detection, and co-immunoprecipitation tests were performed. At 28 days post-HI, neurobehavioral tests, intracisternal EB infusion, Nissl staining, and cerebral blood flow (CBF) evaluations were performed. The results showed that melatonin improved neurological function, restored glymphatic function, maintained blood-brain barrier integrity, alleviated brain edema, increased CBF, and reduced brain atrophy; both melatonin and roscovitine inhibited cyclin-dependent kinase 5 (CDK5) activity, enhanced the interaction between AQP4 and alpha-syntrophin (α-Syn), and maintained AQP4 polarity. In conclusion, the current study suggests that melatonin may enhance the interaction between AQP4 and α-Syn by inhibiting CDK5 activity after HI to maintain glymphatic function.

Mast cells (MCs) degranulation is responsible for the occurrence and development of neuroinflammation after hypoxic-ischemic encephalopathy (HIE). Stromal interaction molecule 1 (STIM1) serves as a Ca2+ sensor on the endoplasmic reticulum. It has been demonstrated that the supression of STIM1 impedes degranulation of MCs in numerous prior investigations. This study aimed to explore the impact of edaravone, an oxygen radical scavenger, on MCs degranulation in HIE rat model, and to explore the contribution of reactive oxygen species (ROS)/STIM1 pathway in mediating MCs degranulation. Nine-day old undetermined gender rat pups were experienced hypoxic-ischemic (HI) injury and edaravone was administered intraperitoneally at 10 min after HI insults. CM4620, an inhibitor of STIM1, was administered intraperitoneally at 10 min after HI insults to elucidate the possible mechanisms. TTC staining, Western blot analysis, immunofluorescence staining, brain water content, cerebral blood flow, toluidine blue staining, Nissl staining, and neurobehavioral test were conducted. The results demonstrated that tryptase, STIM1, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were increased after HI, and edaravone significantly improved neurobehavioral outcomes, reduced brain water content, decreased infarct area, reduced the accumulation of ROS, decreased the degranulation of MCs, and downregulated the protein expression of tryptase, STIM1, IL-6 and TNF-α. CM4620 inhibited MCs degranulation and downregulated the expression of STIM1, tryptase, IL-6, TNF-α. In conclusion, the current investigation revealed that edaravone attenuates MCs degranulation and neuroinflammation, at least partially, via ROS/STIM1 pathway after HI injury.

RATIONALE AND OBJECTIVE:To investigate the cerebral iron content and glymphatic function in newborns with HIE. METHODS:A total of 57 newborns with HIE, aged 1-28 days, were prospectively selected to constitute the HIE group. Meanwhile, 50 healthy newborns were selected as the control group. All the newborns underwent T1 Flair, T2 Flair, 3D-T1, ESWAN, and DTI sequence scans. Subsequently, software processing was performed to obtain the QSM values reflecting iron contents in brain regions and the DTI-ALPS values evaluating the function of glymphatic system. Comparative analysis of the QSM and DTI-ALPS values between the two groups were carried out to identify the characteristic parameters in the brain regions of newborns with HIE. ROC curve analysis was then utilized to detect the sensitivity of QSM value and DTI-ALPS index. RESULTS:In newborns with HIE, the QSM values in the frontal lobe, temporal lobe, and basal ganglia were significantly elevated (P < 0.05). the DTI-ALPS values were notably decreased (P < 0.05). The QSM values in different brain regions such as the frontal lobe, temporal lobe, and basal ganglia were respectively negative correlated with the DTI-ALPS value. The QSM values of the frontal lobe, temporal lobe and basal ganglia, in combination with the DTI-ALPS values, facilitated the discrimination of newborns with HIE from those in the control group (P < 0.05). CONCLUSION:In newborns with HIE, a significant increase in brain iron content was manifested, concomitant with a compromised glymphatic dysfunction. KEY POINTS AND CLINICAL RELEVANCE STATEMENT.

OBJECTIVE:Infantile epileptic spasms syndrome (IESS) and self-limited infantile epilepsy (SeLIE) are both genetically heterogeneous disorders during infancy with distinct prognoses. To better define the genetic spectrum of IESS, we performed a comparative genetic analysis using SeLIE cases as a reference group. METHODS:We performed whole-exome sequencing in a Chinese cohort comprising 54 parent-offspring trios with IESS and 37 trios or quartets with SeLIE. RESULTS:Causal pathogenic or likely pathogenic variants were identified in 61% (56/92) of patients, distributed across 20 different genes. Among these, 10 (29%) variants were novel. A definitive genetic diagnosis was achieved in 37% (20/54) of IESS patients, involving 17 distinct genes, indicating a high degree of genetic heterogeneity. In contrast, SeLIE patients had a much higher diagnostic yield of 95% (36/38), with variants concentrated in only four genes. By comparing de novo mutations in protein-coding regions between the IESS and SeLIE cohorts, we identified both shared and potentially novel variants. Notably, there was a trend toward an increased burden of de novo loss-of-function variants in IESS compared to SeLIE. Among IESS patients, 51.9% (28/54) responded to initial hormonal therapy, while 38.9% (21/54) failed to respond. SIGNIFICANCE:These integrative genomic analyses provide new insights into the pathogenesis of IESS, underscoring a more complex and heterogeneous genetic landscape in IESS compared to SeLIE. PLAIN LANGUAGE SUMMARY:This study investigated the genetic architecture of two infantile epilepsy syndromes: IESS and SeLIE. We demonstrated that IESS has a more heterogeneous genetic background, whereas SeLIE is associated with more specific variants. These findings provide novel insights into the genetic underpinnings of IESS.

Bilirubin encephalopathy (BE) is a neurological disorder caused by the accumulation of unconjugated bilirubin (UCB) in the brain of newborns, resulting in various degrees of neuronal impairment. BE is characterized by cytotoxic edema and neuronal apoptosis. Aquaporin-4 (AQP4), a water channel abundantly expressed in the central nervous system, plays a critical role in maintaining water homeostasis. Dysregulation of AQP4 expression or trafficking is closely associated with brain edema, suggesting that modulation of AQP4 may offer a potential therapeutic approach for BE. Previous studies have indicated that melatonin (MT) possesses neuroprotective and therapeutic potential against BE; however, its precise mechanisms remain unclear. In this study, we optimized rat BE model to investigate the therapeutic effects of melatonin on AQP4 expression, trafficking, and apoptosis in parietal cortical neurons. Furthermore, we explored the molecular mechanisms underlying melatonin’s neuroprotective actions, including the regulation mechanism of AQP4 expression, brain edema formation, and apoptosis induced by UCB accumulation. The results indicate that in the BE model, pathological injury of parietal cortex was significantly aggravated and AQP4’s expression peaked at 24 h after BE modeling. MT activated PI3K/AKT signaling pathway in rat parietal cortex to downregulate AQP4 expression, apoptosis related proteins, and decreased SNX27’s expression to promote the internalization of AQP4, reducing bilirubin induced cytotoxic edema and cortical apoptosis. This data suggest that MT has a neuroprotective role in BE, by potentially delaying its progression.

Background: Activation of mast cells plays an important role in brain inflammation. CD300a, an inhibitory receptor located on mast cell surfaces, has been reported to reduce the production of pro-inflammatory cytokines and exert protective effects in inflammation-related diseases. Peroxisome proliferator-activated receptor beta/delta (PPAR(beta/delta)), a ligand-activated nuclear receptor, activation upregulates the transcription of CD300a. In this study, we aim to investigate the role of PPAR(beta/delta) in the attenuation of germinal matrix hemorrhage (GMH)-induced mast cell activation via CD300a/SHP1 pathway.Methods: GMH model was induced by intraparenchymal injection of bacterial collagenase into the right hemispheric ganglionic eminence in P7 Sprague Dawley rats. GW0742, a PPAR(beta/delta) agonist, was administered intranasally at 1 h post-ictus. CD300a small interfering RNA (siRNA) and PPAR(beta/delta) siRNA were injected intracerebroventricularly 5 days and 2 days before GMH induction. Behavioral tests, Western blot, immunofluorescence, Toluidine Blue staining, and Nissl staining were applied to assess post-GMH evaluation.Results: Results demonstrated that endogenous protein levels of PPAR(beta/delta) and CD300a were decreased, whereas chymase, tryptase, IL-17A and transforming growth factor beta 1 (TGF-beta 1) were elevated after GMH. GMH induced significant short- and long-term neurobehavioral deficits in rat pups. GW0742 decreased mast cell degranulation, improved neurological outcomes, and attenuated ventriculomegaly after GMH. Additionally, GW0742 increased expression of PPAR(beta/delta), CD300a and phosphorylation of SHP1, decreased phosphorylation of Syk, chymase, tryptase, IL-17A and TGF-beta 1 levels. PPAR(beta/delta) siRNA and CD300a siRNA abolished the beneficial effects of GW0742.Conclusions: GW0742 inhibited mast cell-induced inflammation and improved neurobehavior after GMH, which is mediated by PPAR(beta/delta)/CD300a/SHP1 pathway. GW0742 may serve as a potential treatment to reduce brain injury for GMH patients.

Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/β-dystroglycan (β-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10 min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of β-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood–brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated β-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/β-DG pathway after ICH.

Retinal ischemia-reperfusion (I/R) injury is a common pathophysiological stress state connected to various diseases, including acute glaucoma, retinal vascular obstruction, and diabetic retinopathy. Recent studies have suggested that geranylgeranylacetone (GGA) could increase heat shock protein70 (HSP70) level and reduce retinal ganglion cells (RGCs) apoptosis in a rat retinal I/R model. However, the underlying mechanism remains unclear. Moreover, the injury caused by retinal I/R includes not only apoptosis but also autophagy and gliosis, and the effects of GGA on autophagy and gliosis have not been reported. Our study established a retinal I/R model by anterior chamber perfusion pressuring to 110 mmHg for 60 min, followed by 4 h of reperfusion. The levels of HSP70, apoptosis-related proteins, GFAP, LC3-II, and PI3K/AKT/mTOR signaling proteins were determined by western blotting and qPCR after treatment with GGA, HSP70 inhibitor quercetin (Q), PI3K in-hibitor LY294002, and mTOR inhibitor rapamycin. Apoptosis was evaluated by TUNEL staining, meanwhile, HSP70 and LC3 were detected by immunofluorescence. Our results demonstrated that GGA-induced HSP70 expression significantly reduced gliosis, autophagosome accumulation, and apoptosis in retinal I/R injury, indicating that GGA exerted protective effects on retinal I/R injury. Moreover, the protective effects of GGA mechanistically relied on the activation of PI3K/AKT/mTOR signaling. In conclusion, GGA-induced HSP70 overexpression has protective effects on retinal I/R injury by activating PI3K/AKT/mTOR signaling.

阿尔茨海默病(AD)是一种不可逆的神经退行性疾病,其病理特征主要为β 淀粉样蛋白(Aβ)沉积形成老年斑、神经元内神经纤维缠结和神经元丢失[1]. AD的病因及其发病机制十分复杂,目前认为是由环境及遗传等多种因素共同作用导致的,至今尚无有效的治疗及延缓疾病发展的方法[2] . 患者会出现认知功能、精神和行为障碍,从而导致其日常生活能力的逐渐下降,严重影响患者的生活质量,同时也增加了家庭和社会的负担. 随着人口老龄化趋势加剧,AD的发病率明显升高[3] ,因此阐明AD的病因、发病机制及制定相应治疗方案就成为亟待解决的问题. 有关 AD 发病机制目前存在多种假说,如经典的Aβ异常沉积假说、神经炎症假说、Tau蛋白过度磷酸化与载脂蛋白(Apo)E基因异常表达假说等. 近年来,有学者提出神经元能量代谢障碍对AD的发生发展有重要作用[3,4] . 目前,国内与能量代谢障碍方面基础机制与发展过程研究的综述文献较少. 本文以神经元能量代谢障碍为切入点,分别从星形胶质细胞-神经元穿梭(ANLS)机制障碍及神经元线粒体能量代谢障碍 2 个假说出发,对能量代谢障碍在AD发病过程中的作用及相关研究进行综述.

BACKGROUND:Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol-requiring enzyme-1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism.METHODS:A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR-25 and agomiR-25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT-qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed.RESULTS:Endogenous phosphorylated IRE1α (p-IRE1α), miR-25-3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR-25-3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR-25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR-25 reversed the effects promoted by KIRA6.CONCLUSION:The IRE1α phosphokinase activity is involved in the oxidative stress response through miR-25/Nox4 pathway in the mouse ICH brain.

目的:探讨槲皮素(quercetin)对脑出血(ICH)小鼠氧化应激及神经功能的影响.方法:建立小鼠脑出血模型后通过改良Garcia评分和转角试验评估各组小鼠神经功能;通过脑含水量、脑血红蛋白含量检测和苏木精-伊红(HE)染色染色评估各组小鼠大脑受损程度与组织形态变化;通过Western Blot检测各组小鼠核因子E2相关因子2(Nrf2)和NADPH氧化酶4(Nox4)蛋白的表达水平;通过超氧化物阴离子荧光探针(DHE)和过氧化氢(H2O2)检测各组小鼠的氧化应激水平.结果:与假手术组相比,脑出血组小鼠神经功能受损,脑含水量和血红蛋白含量升高,脑组织病理结构损伤,Nrf2表达无明显变化,Nox4表达升高,氧化应激水平升高;与脑出血组相比,槲皮素组小鼠的神经功能障碍减轻,脑含水量和血红蛋白含量降低,脑组织病理结构损伤减轻,Nrf2表达升高,Nox4表达降低,氧化应激水平降低.结论:槲皮素对脑出血小鼠的神经功能具有保护作用,可能通过抑制Nox4表达水平,增强Nrf2表达水平以降低氧化应激损伤来实现.

目的:研究丙泊酚(propofol)减轻大鼠脑出血(ICH)后神经功能损伤与肥大细胞脱颗粒的关系.方法:右侧大脑基底核注射尾部自体血制备SD大鼠脑出血模型,脑出血后30 min经股静脉泵注丙泊酚.模型制备后采用改良的Garcia实验和corner turns实验检测大鼠神经功能,分光光度计检测伊文思蓝含量,干湿比检测脑含水量,Western Blot检测类胰蛋白酶、糜蛋白酶、IL-1β和TNF-α的表达,荧光染色实验和甲苯胺蓝染色实验检测肥大细胞数量.结果:与对照组相比,脑出血组大鼠神经功能评分减少(P＜0.05),伊文思蓝含量以及脑含水量升高(P＜0.05),类胰蛋白酶、糜蛋白酶、IL-β和TNF-α表达增多(P＜0.05),肥大细胞数量增加;与脑出血组相比,丙泊酚组大鼠神经功能评分增高(P＜0.05),伊文思蓝含量以及脑含水量降低(P＜0.05),类胰蛋白酶、糜蛋白酶、IL-1β和TNF-α表达减少(P＜0.05),肥大细胞数量减少.结论:丙泊酚抑制肥大细胞脱颗粒减轻大鼠脑出血后神经功能损伤.

The degranulation of mast cells accounts for the development of neuroinflammation following intracerebral hemorrhage (ICH). Inhibition of IRE1α, a sensor signaling protein related to endoplasmic reticulum stress, has been shown to exert anti-inflammatory effects in several neurological diseases. The objective of this study was to investigate the effects of IRE1α inhibition on mast cells degranulation in an ICH mouse model and to explore the contribution of miR-125/Lyn pathway in IRE1α-mediated mast cells degranulation. Male mice were subjected to ICH by intraparenchymal injection of autologous blood. STF083010, an inhibitor of IRE1α, was administered intranasally at 1 h after ICH induction. AntimiR-125 was delivered by intracerebroventricular (i.c.v.) injection prior to ICH induction to elucidate the possible mechanisms. Western blot analysis, immunofluorescence staining, neurological test, hematoma volume, brain water content, toluidine blue staining and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were performed. Endogenous phosphorylated IRE1α (p-IRE1α), tryptase, interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α) and tryptase mRNA were increased in time dependent manner while miR-125b-2-3p was decreased after ICH. Inhibition of IRE1α, with STF083010, remarkably reduced brain water content, improved neurological function, decreased hematoma volume, upregulated the expression of miR-125b-2-3p, decreased the number of mast cells, and downregulated the protein expression of Lyn kinase, XBP1s (spliced X-box binding protein-1), tryptase, IL-17A and TNF-α. The downregulation of Lyn kinase, tryptase, IL-17A, TNF-α, and decreased mast cells number were reversed by antimiR-125. The present findings demonstrate that IRE1α inhibition attenuates mast cells degranulation and neuroinflammation, at least partially, through IRE1α/miR-125/Lyn signaling pathway after ICH.

(AQP4) regulates retinal water homeostasis and participates in retinal oedema pathophys-iology. p-dystroglycan (p-DG) is responsible for AQP4 polarization and can be cleaved by matrix metalloproteinase-9 (MMP9). Retinal oedema induced by ischemia-reperfusion (I/R) injury is an early complica-tion. Bumetanide (BU) has potential efficacy against cytotoxic oedema. Our study investigated the effects of p -DG cleavage on AQP4 and the roles of BU in a rat retinal I/R injury model. The model was induced by applying 110 mm Hg intraocular pressure to the anterior eye chamber. BU and U0126 (a selective ERK inhibitor) were intraperitoneally administered 15 and 30 min, respectively, before I/R induction. Rhodamine isothiocyanate extravasation detection, quantitative real-time PCR, transmission electron microscopy, hematoxylin-eosin stain-ing, immunofluorescence staining, western blotting, and TUNEL staining were performed. AQP4 lost its polariza-tion in the retinal perivascular domain as a result of p-DG cleavage. BU rescued AQP4 depolarization, suppressed AQP4 protein expression, attenuated retinal cytotoxic oedema, and downregulated p-DG and AQP4 mRNA expres-sion. BU suppressed glial responses and mitochondria-mediated apoptotic protein expression, including that of Caspase-3 and Cyto C, raised the Bcl-2/Bax ratio, and lowered the number of apoptotic cells in the retina. Both BU and U0126 downregulated p-ERK and MMP9 expression. Thus, BU treatment suppressed p-DG cleavage, recov-ered AQP4 polarization partially via inhibiting ERK/MMP9 signaling pathway, and possess potential neuroprotec-tive efficacy in the rat retinal ischemia-reperfusion injury model.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment.

Bilirubin encephalopathy (BE) is a neurological syndrome in newborns, mainly caused by neuronal injury due to excessive oxidative stress produced by unconjugated bilirubin (UCB). Neuroglobin (NGB) can protect the brain by removing oxidative stress species, but its expression and significance in BE are not clear. To address this question, the neonatal BE model was established by injecting UCB into the cerebellomedullary cistern of 7-day-old SD rats. Rats were divided into a sham and BE 6 hr group, BE 12 hr group, BE 24 hr group, and BE 7 d group according to UCB action times. Hematoxylin/eosin and Nissl staining, and electron microscopy were employed to observe the pathological and ultrastructural changes of nerve cells in each group. Immunofluorescence staining was used to detect NGB expression sites and cell types. Western blotting and quantitative PCR served to detect NGB expression and test the mitochondrial apoptosis signal pathway. The results confirm that UCB can lead to pathological damage and ultrastructural changes in rats' temporal cortex, increasing the expression of apoptosis-related proteins Bax, Bcl-2, Cyt c, Caspase-3, and neuronal NGB. UCB promotes NGB expression with an increase in action time and reach a peak at 12 hr. In summary, brain damage induced by UCB will cause an increase in NGB expression, the increasing NGB can inhibit neuron apoptosis in early BE phases. Therefore, promoting the expression of endogenous NGB, to act as a neuroprotective agent may be a potential treatment strategy for BE.

考试是检验学生对所学知识的掌握程度和评估教师教学质量的手段,对促进学生学习和改进教师教学均起到重要作用[1,2].解剖学课程特点是名词多、描述多、内容枯燥、难记忆,因此,在面对解剖学课程考试时,学生感受压力偏大.而留学生来自世界各地,由于文化的差异,他们在学习过程中重讨论和实践,轻记忆,在解剖学课程的考试中留学生相对中国学生会出现更多困难,引发学生考试纪律涣散、教师出题难度不易把握、阅卷工作任务繁重等问题出现.本教研室自2001年招收首批医学本科留学生以来,在以提高教学效果为中心的留学生考试工作中一直进行着探索和实践.计算机网络技术的发展为教学提供了一个崭新的数字化平台.目前,很多等级考试、水平测试、职业能力测试等已经采用网络考试系统进行测试[3, 4].合理地开发使用医学院校的网络考试系统,将极大地提高解剖学课程任课教师的工作效率,提升留学生解剖学教学质量.