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  • ORIGINAL ARTICLE
    Valeria De Matteis, Simona Martano, Paolo Pellegrino, Chiara Ingrosso, Daniele Costa, Stefano Mazzotta, Jose L. Toca-Herrera, Rosaria Rinaldi, Mariafrancesca Cascione
    Ibrain, 2024, 10(2): 123-133. https://doi.org/10.1002/ibra.12157
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    Neurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts focus on implementing diverse strategies to mitigate the adverse effects of neurodegeneration, with the goal of decelerating the pathology progression. Notably, in recent years, it has emerged that the use of nanoparticles (NPs), particularly those obtained through green chemical processes, could constitute a promising therapeutic approach. Green NPs, exclusively sourced from phytochemicals, are deemed safer compared to NPs synthetized through conventional chemical route. In this study, the effects of green chemistry-derived silver NPs (AgNPs) were assessed in neuroblastoma cells, SHSY-5Y, which are considered a pivotal model for investigating neurodegenerative diseases. Specifically, we used two different concentrations (0.5 and 1 µM) of AgNPs and two time points (24 and 48 h) to evaluate the impact on neuroblastoma cells by observing viability reduction and intracellular calcium production, especially using 1 μM at 48 h. Furthermore, investigation using atomic force microscopy (AFM) unveiled an alteration in Young’s modulus due to the reorganization of cortical actin following exposure to green AgNPs. This evidence was further corroborated by confocal microscopy acquisitions as well as coherency and density analyses on actin fibers. Our in vitro findings suggest the potential efficacy of green AgNPs against neurodegeneration; therefore, further in vivo studies are imperative to optimize possible therapeutic protocols.

  • REVIEW
    Chao Chen, Rui-Xue Zhai, Xin Lan, Sheng-Feng Yang, Si-Jie Tang, Xing-Long Xiong, Yu-Xin He, Jing-Fang Lin, Jia-Rong Feng, Dong-Xu Chen, Jing Shi
    Ibrain, 2024, 10(2): 197-216. https://doi.org/10.1002/ibra.12167
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    This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood–brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

  • REVIEW
    Yan-Li Huang, Zhao-Qiong Zhu
    Ibrain, 2024, 10(2): 217-224. https://doi.org/10.1002/ibra.12021
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    Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and antiinflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.

  • CORRIGENDUM
    Ting-Ting Li, Lan-Chun Zhang, Liu-Lin Xiong, Chang-Yin Yu
    Ibrain, 2024, 10(2): 239-239. https://doi.org/10.1002/ibra.12135
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  • COMMENT
    Doriana Oliveri, Giorgia Moschetti, Anna Griego, Edoardo Scarpa
    Ibrain, 2024, 10(2): 225-230. https://doi.org/10.1002/ibra.12154
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    Recent research has shown that tau protein can be passed to neighboring cells, leading to cellular senescence in the endothelial cells present in the central nervous system (CNS). This discovery could potentially open new doors for testing novel therapeutic compounds that specifically target senescent cells (senolytics) or for identifying new biomarkers that can enable early detection of tauopathies and dementia.

  • ORIGINAL ARTICLE
    Ke-Qian Liu, Xue Bai, Ji-Lin Chen, Guo-Jiao Chen, Muhammad Ameen Jamal, Yu-Qi He
    Ibrain, 2024, 10(2): 172-185. https://doi.org/10.1002/ibra.12131
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    We aim to explore the pharmacological efficacy and molecular network mechanism of Shexiang Huayu Xingnao granules (SX granules) in the treatment of intracerebral hemorrhage (ICH) based on experiments and network pharmacology. After the ICH model establishment, the behavioral functions of rats were assessed by the modified neurological severity score (mNSS), the wire suspension test, and the rotarod test. Brain histomorphological changes were observed using 2,3,5-triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), Nissl, and TdT-mediated dUTP nick end labeling (TUNEL) combined with neuronal nuclear (NEUN) immunofluorescence staining. The cross-targets of SX granules and ICH were obtained using network pharmacology, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were performed. Then, the obtained Hub genes were verified using real-time quantitative polymerase chain reaction (RT-qPCR). The mNSS score was reduced and the duration to remain wire suspended increased in the SX group. In the morphological experiment, SX granules reduced brain tissue damage, neuronal apoptosis, and the number of astrocytes in the ICH rats. Moreover, 607 targets of drug-disease intersection were obtained by network pharmacology, and 10 Hub genes were found. SX granules regulated the expression of HRAS, MAPK3, and STAT3 in ICH condition. In conclusion, SX granules improved behavioral dysfunction, abnormal alterations in brain tissue, and cell morphology in ICH rats, and potential molecular mechanism was linked with the expression of multiple genes.

  • ORIGINAL ARTICLE
    Yue Hu, Yong Ye, Hui Lin, Jun-Jie Chen, Ting-Ting Sun, Gong-Wei Zhang, Na Wang, Yuan-Hang Shu, Xue Gong, Fei-Fei Ran, Jia-Li Zhang, Yong Tao
    Ibrain, 2024, 10(2): 186-196. https://doi.org/10.1002/ibra.12073
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    This study aimed to explore whether the combined application of desflurane and dexmedetomidine (Dex) reduces the occurrence of postoperative neurocognitive disorders (PND) in patients. We selected patients in our hospital who underwent surgery under general anesthesia, and divided them into two groups: Dex and desflurane (Dex + Des) and desflurane (Des) groups. The data of patients were collected and the Mini-Mental State Examination (MMSE) score was used to assess cognitive status. The blood cell counts were determined preoperatively and on postoperative days 1, 3, and 6, and the percentage of neutrophils and lymphocytes were also recorded. The statistical methods used were the independent-samples t-test and the x2 test. Pearson’s correlation was used to analyze the correlation between PND and inflammation. The incidence of PND in the Dex + Des group was lower than that in the Des group. The postoperative MMSE scores in the Dex + Des group were higher than those in the Des group (p = 0.032). The percentage of neutrophils in the Dex + Des group was significantly lower than that in the Des group on the first and third days after surgery (p = 0.007; p = 0.028). The MMSE scores on the first day after surgery were negatively correlated with the multiple changes in white blood counts and the percentage of neutrophils (r = −0.3038 and −0.3330). Dex combined with Des reduced the incidence of PND and reduced the postoperative inflammatory cell counts.

  • ORIGINAL ARTICLE
    Giulio Perrotta
    Ibrain, 2024, 10(2): 146-163. https://doi.org/10.1002/ibra.12148
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    The Perrotta Integrative Clinical Interview, second version (PICI-2) requires structural and functional updates, based on clinical and academic experience, especially in terms of functional traits and interpretation of psychopathological disorders. The Perrotta Integrative Clinical Interviews-3 (PICI- 3) was created and structured into four sections, dedicated to dysfunctional traits in children and pre-adolescents (PICI-C-3, 8–13 years) and in adolescents, adults, and the elderly (PICI-TA-3, 14–90 years), to common secondary disorders (PICI-DS-3, 8–90 years) and functional traits (PICI-FT-3, 8–90 years), with the identification of all functional elements and structural aspects of personality according to the model underlying the PICI (IPM). Selecting 1732 subjects, between 8 and 90 years old, the statistical analysis showed that the psychometric test has a well-defined and stable construct, with the variables well represented and positively correlated with other constructs already validated. In particular: (a) the PICI-TA-3 (Section A) was compared with the Minnesota Multiphasic Personality Inventory-2- Restructured Form (MMPI-2-RF), obtaining 99.3% compatibility of results, with a Pearson’s coefficient (R) of 0.999 and p 0.001; (b) the PICI-C-3 (Section B) was compared with the Child Behavior Checklist (CBCL), obtaining 94.1% compatibility of results, with a Pearson coefficient (R) of 0.969 and p < 0.001; (c) the PICI-FT-3 (Section D) was compared with the Big Five Personality Test (Big5), obtaining 89.4% compatibility of results, with a Pearson coefficient (R) of 0.797 and p < 0.001. The PICI-3 is a valid, efficient, and effective psychometric tool to identify the functioning or dysfunction of personality traits for psychopathological diagnosis.

  • ORIGINAL ARTICLE
    Hong-Su Zhou, Jing Li, Yi-Huan Guan, Hua He, Li-Ren Huang Fu
    Ibrain, 2024, 10(2): 164-171. https://doi.org/10.1002/ibra.12075
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    This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals.We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

  • CASE REPORT
    Zhong Luo, Piao Cao, Chun-Lin Zhang, Zu-Cai Xu, Ping Xu, Tao Liang
    Ibrain, 2024, 10(2): 231-237. https://doi.org/10.1002/ibra.12093
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    The incidence of incomplete partition Type I inner ear malformation is very low; therefore, bacterial meningitis caused by this malformation is also rare. Here, we report a case of such a patient. This case is a young female patient, who is 7 years old, began to have recurrent headaches, and after 5 years, also began to have chest and back pain. The doctor diagnosed meningitis, and the anti-infection treatment was effective. She was followed up annually and continued to have outbreaks repeatedly for 17 years, but the cause of repeated infection was not found. After a detailed diagnosis and treatment in our hospital, the patient was finally diagnosed with incomplete partition Type I inner ear malformation, resulting in repeated bacterial meningitis. The patient recovered well after surgical treatment, and the symptoms did not recur after 1-year follow-up.

  • CORRIGENDUM
    Ting-Ting Li, Hao Yuan
    Ibrain, 2024, 10(2): 238-238. https://doi.org/10.1002/ibra.12134
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  • ORIGINAL ARTICLE
    Ting-Ting Li, Lu Yin, Yue-Xin Huang, Xiu-Hong Wang, Yan-Huan Wei, Yong Wang, Shi-Wei Yang, Genoveva B. da Graca Cunha, Fei Liu
    Ibrain, 2024, 10(2): 134-145. https://doi.org/10.1002/ibra.12163
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    This study aimed to evaluate the efficacy and safety of remimazolam for intraoperative sedation during regional anesthesia. It was a phase II-multicenter, randomized, single-blind, parallel-group, active-controlled clinical trial (No. ChiCTR2100054956). From May 6, 2021 to July 4, 2021, patients were randomly enrolled from 17 hospitals in China. A total of 105 patients aged 18–65 years who underwent selective surgery under regional anesthesia were included. Patients received different sedatives with different dosages: 0.1 mg/kg remimazolam (HR), 0.05 mg/kg remimazolam (LR), or 1.0 mg/kg propofol (P) group, followed by a maintenance infusion. Main outcome measures included the efficacy of sedation measured by Modified Observer’s Assessment of Alertness/Sedation Scale (MOAA/S) levels (1–4, 1–3, 2–3, 3, and 2–4) during the sedation procedure (the duration percentage) and incidence of adverse reactions. It showed that the duration percentage of MOAA/S levels 1–4 was 100.0 [8.1]% (median [interquartile range]), 89.9 [20.2]%, 100.0 [7.7]% in the HR, LR, and P groups, respectively. The percentage of patients in the HR, LR, and P groups who achieved MOAA/S levels 1–4 within 3 min after administration was 85.7%, 58.8%, and 82.9%, respectively. However, the time to recovery from anesthesia after withdrawal of sedatives (7.9 ± 5.7 min), incidence of anterograde amnesia (75%), and adverse effects were not statistically significant among the three groups. These findings suggest that a loading dose of remimazolam 0.1 mg/kg followed by a maintenance infusion of 0–3 mg/kg/h provides adequate sedation for patients under regional anesthesia without increasing adverse reactions.