Cerebellar abscess secondary to metastatic lung adenocarcinoma: a case report.

BACKGROUND: Cerebellar abscesses are rare, life-threatening infections often originating from bacterial sources, while metastatic brain lesions from lung adenocarcinoma are relatively common. However, the coexistence of a cerebellar abscess secondary to metastatic lung adenocarcinoma is exceedingly rare and presents unique diagnostic and management challenges. CASE PRESENTATION: We report a case of a 35 year-old Pakistani female patient with persistent headaches, nausea, and vertigo, who was found to have a large cerebellar mass with features suggestive of metastatic lung adenocarcinoma. Further investigation revealed a concomitant cerebellar abscess. Surgical excision and broad-spectrum antibiotics were initiated, resulting in a favorable outcome. CONCLUSION: This case showcases the rarity and complexity of cerebellar abscesses due to metastatic lung adenocarcinoma. Timely intervention, including surgery and targeted therapy, is crucial for successful management. Further research is needed to enhance treatment strategies.

[Establishment of an Engineered Bacterial Membrane Biomimetic Nanodrug Delivery System and Its Role in the Treatment of Glioma]. / å·¥ç¨‹åŒ–ç»†èŒè†œä»¿ç”Ÿçº³ç±³è¯ç‰©é€’é€ç³»ç»Ÿçš„å»ºç«‹åŠåœ¨è„‘èƒ¶è´¨ç˜¤æ²»ç–—ä¸­çš„ä½œç”¨ç ”ç©¶.

Objective: To develop engineered bacterial membrane biomimetic nanoparticles, Angiopep-2 E. coli membrane (ANG-2 EM)@PDA-PEI-CpG (ANG-2 EM@PPC), for efficient targeted drug delivery in the treatment of glioma, and to provide theoretical and technical support for targeted glioma therapy. Methods: The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory, and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation. ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes. Western blotting, agarose gel electrophoresis, and transmission electron microscopy (TEM) were used to verify the preparation. Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC. Regarding cell experiments, CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils. A flow chamber model was designed and constructed, and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment. Neutrophil death patterns were characterized by fluorescence microscopy, and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced. Regarding animal experiments, a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified. The tumor model mice were divided into three groups, including DiR group, EM@PPC group, and ANG-2 EM@PPC group (all n=3), which were injected with DiR, ANG-2 EM@PDA-PEI-CpG, and EM@PDA-PEI-CpG via the tail vein, respectively (all at 10 mg/kg). Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain. The tumor model mice were further divided into PBS group, PDA group, PC group, PPC group, EM@PPC group, and ANG-2 EM@PPC group (all n=4), which were injected with PBS, PDA, PC, PPC, EM@PPC, and ANG-2 EM@PPC injected via the tail vein, respectively (all at 10 mg/kg). Imaging was performed in vivo to observe tumor regression, and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics. TUNEL staining (brain tissue) and HE staining (brain, heart, liver, spleen, lung and kidney tissues) were performed to evaluate the therapeutic effect. Results: The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles, with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm. Due to the coating of ANG-2 EM, the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm, with a clear bacterial membrane layer on the surface. Stability was maintained for at least one week. ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay. Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition. Compared with the EM@PPC group, the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced (uptake efficiency 24.9% vs. 31.1%). Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis (NETosis) to apoptosis. Western blot confirmed the production of neutrophil apoptotic bodies, and flow cytometry showed that the production rate was as high as 77.7%. Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs (heart, liver, spleen, lungs, and kidney) in the DiR group, the EM@PPC gropu, and the ANG-2 EM@PPC group (P>0.05), but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group (P<0.05). Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier (BBB), and exhibited high affinity to and internalization by neutrophils located in brain tumors. Compared with PBS, PDA, PC, and PPC groups, the survival rate and body mass of mice in the EM@PPC group were improved, tumor fluorescence intensity was weakened, and apoptotic cells were increased. These trends were even more prominent in the ANG-2 EM@PPC group. No abnormality was found in the HE staining of any group. Conclusion: An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared, capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy. This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Predicting intraoperative major blood loss in microsurgery for brain arteriovenous malformations.

Objective: Intraoperative blood loss poses a great challenge for brain arteriovenous malformation (AVM) microsurgery, although systematic researches are still lacking. This study aimed to identify factors predicting intraoperative major blood loss in brain AVM microsurgery and to investigate its impact on patient outcome. To deal with the fierce bleeding, we introduced a modified hemostatic method, bone-wax (BW) coated bipolar electrocoagulation. Methods: The authors retrospectively analyzed the clinical data of 131 patients (50/81 in intraoperative major/non-major blood loss cohort) with brain AVMs who underwent microsurgery in our center during the period between January 2018 and April 2023. According to previous studies, major blood loss was defined as blood loss of at least 1,000 mL. The accuracy and objectivity of our grouping methodology were validated by comparing the hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding. Potential clinical and radiological predictors for intraoperative major blood loss were evaluated using a multivariate stepwise logistic regression. And outcomes of patients in the two cohorts were also compared. At last, the performance of BW coated bipolar electrocoagulation in brain AVM microsurgery was illustrated by the case presentation, histological staining and transmission electron microscopy of the coagulated nidus vessels. Results: Hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding were significant different between the two cohorts. five independent factors predicting intraoperative major blood loss were identified: (1) clinical manifestations; (2,3) location and size of the nidus; (4) deep venous drainage; and (5) the number of draining veins. And the intraoperative major blood loss can not only adversely affect the surgical progression, but also predict poor perioperative outcomes for patients. Regarding the application of BW coated bipolar electrocoagulation, we found the novel hemostatic method exerted efficient hemostatic effect and reduced the damage to the vascular structure in brain AVM microsurgery. Conclusion: This study proposed a nomogram for neurosurgeons to predict intraoperative major blood loss in brain AVM microsurgery preoperatively. And intraoperative major blood loss is associated with poor patient outcomes. In addition, BW coated bipolar electrocoagulation, can be applied to control ferocious bleeding during brain AVM microsurgery, which still remains further researches.

Longitudinal assessment of glymphatic changes following mild traumatic brain injury: Insights from perivascular space burden and DTI-ALPS imaging.

Introduction: Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. Methods: In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Results: Our key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information. Conclusion: ePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy.

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3ß. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway.

Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis.

Objective: Investigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability. Methods: Participants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition. Results: Participants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS<3). This resulted in lower E/I ratios in the higher disability group. Individuals with higher disability presented with asymmetrical E/I ratios between brain hemispheres, a pattern not present in the group with lower disability. In regression analyses controlling for demographics, lowered TMS-probed E/I ratio predicted variance in disability (R2 = 0.37, p < 0.001), upper extremity function (R2 = 0.35, p < 0.001), walking speed (R2 = 0.22, p = 0.005), and cognitive performance (R2 = 0.25, p = 0.007). Receiver Operating Characteristic curve analysis confirmed 'excellent' discriminative ability of the E/I ratio in distinguishing high and low disability. Finally, excitation superiorly correlated with the E/I ratio than overall inhibition in both hemispheres (p ≤ 0.01). Conclusion: The E/I ratio is a potential neurophysiological biomarker of disability level in MS, especially when assessed in the hemisphere corresponding to the weaker body side. Interventions aimed at increasing cortical excitation or reducing inhibition may restore E/I balance potentially stalling progression or improving function in MS.

A female adult-onset X-ALD patient with pure cerebellar symptoms:a case report.

X-linked adrenoleukodystrophy (X-ALD) caused by ATP-binding cassette subfamily D member 1 (ABCD1) gene defects is the most common inherited peroxisomal disorder.The female cerebello-brainstem dominant type in which cerebellum and brainstem are mainly involved is very rare. We report a 40-year-old female who was diagnosed as the rare disorder with magnetic resonance imaging (MRI) and genetic analysis mainly. Her initial symptoms were progressive slurred speech and writing disturbance. Her brain MRI showed obvious atrophy of brainstem and cerebellum. She did not have adrenal insufficiency. Genetic analysis showed a heterozygous missense mutation in exon 4 of the coding region of ABCD1 (c.1252C > T, p.Arg418Trp).This is the first report of this particular mutation being associated with the cerebello-brainstem dominant phenotype of X-ALD, as well as the first description of this X-ALD variant in a (heterozygous) female patient.X-ALD should be considered in young and middle-aged patients with slow-progressing ataxia and dysarthria.

Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.

Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

Navigating the neurological frontier: Macromolecular marvels in overcoming blood-brain barrier challenges for advanced drug delivery.

The blood-brain interface poses formidable obstacles in addressing neurological conditions such as Alzheimer's, Multiple Sclerosis, brain cancers, and cerebrovascular accidents. Serving as a safeguard against potential threats in the blood, this barrier hinders direct drug delivery to affected cells, necessitating specialized transport mechanisms. Within the realm of nanotechnology, the creation of nanoscale carriers, including macromolecules such as polymers, lipids, and metallic nanoparticles, is gaining prominence. These carriers, tailored in diverse forms and sizes and enriched with specific functional groups for enhanced penetration and targeting, are capturing growing interest. This revised abstract explores the macromolecular dimension in understanding how nanoparticles interact with the blood-brain barrier. It re-evaluates the structure and function of the blood-brain barrier, highlighting macromolecular nanocarriers utilized in drug delivery to the brain. The discussion delves into the intricate pathways through which drugs navigate the blood-brain barrier, emphasizing the distinctive attributes of macromolecular nanocarriers. Additionally, it explores recent innovations in nanotechnology and unconventional approaches to drug delivery. Ultimately, the paper addresses the intricacies and considerations in developing macromolecular-based nanomedicines for the brain, aiming to advance the creation and evolution of nanomedicines for neurological ailments.

Application of eye and hand interventions in brain magnetic resonance imaging of young children.

Objective: To explore the feasibility of eye and hand interventions in young children during brain magnetic resonance imaging (MRI). Methods: A total of 414 4- to 6-year-old children who underwent brain MRI at our hospital were randomly divided into 4 groups: the routine posture group (n = 105), eye mask group (n = 102), fixed hand apron group (n = 108), and eye mask and fixed hand apron group (n = 99). All the children underwent brain MRI when they were awake (without using sedatives). The success rate of brain MRI and the quality of brain MR images were compared among the four groups. Results: The success rate of brain MRI was the highest in the eye mask and fixed hand apron group (94.9 %), followed by the eye mask group (85.3 %) (P < 0.05). The brain MR image quality was the best for children wearing eye masks and fixed hand aprons (5 points, 69 patients), followed by those wearing eye masks (5 points, 53 patients) (P < 0.05). Conclusion: When children undergo brain MRI, simultaneous eye and hand interventions can greatly improve the success rate of the examination and the quality of MR images. This study protocol was registered at the Chinese clinical trial registry (ChiCTR2100050248).

The decoder design and performance comparative analysis for closed-loop brain-machine interface system.

Brain-machine interface (BMI) can convert electroencephalography signals (EEGs) into the control instructions of external devices, and the key of control performance is the accuracy and efficiency of decoder. However, the performance of different decoders obtaining control instructions from complex and variable EEG signals is very different and irregular in the different neural information transfer model. Aiming at this problem, the off-line and on-line performance of eight decoders based on the improved single-joint information transmission (SJIT) model is compared and analyzed in this paper, which can provide a theoretical guidance for decoder design. Firstly, in order to avoid the different types of neural activities in the decoding process on the decoder performance, eight decoders based on the improved SJIT model are designed. And then the off-line decoding performance of these decoders is tested and compared. Secondly, a closed-loop BMI system which combining by the designed decoder and the random forest encoder based on the improved SJIT model is constructed. Finally, based on the constructed closed-loop BMI system, the on-line decoding performance of decoders is compared and analyzed. The results show that the LSTM-based decoder has better on-line decoding performance than others in the improved SJIT model.

Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers.

Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

Association of chronotype with language and episodic memory processing in children: implications for brain structure.

Introduction: Chronotype refers to individual preference in circadian cycles and is associated with psychiatric problems. It is mainly classified into early (those who prefer to be active in the morning and sleep and wake up early) and late (those who prefer to be active in the evening and sleep and wake up late) chronotypes. Although previous research has demonstrated associations between chronotype and cognitive function and brain structure in adults, little is known regarding these associations in children. Here, we aimed to investigate the relationship between chronotype and cognitive function in children. Moreover, based on the significant association between chronotype and specific cognitive functions, we extracted regions-of-interest (ROI) and examined the association between chronotype and ROI volumes. Methods: Data from 4,493 children (mean age of 143.06 months) from the Adolescent Brain Cognitive Development Study were obtained, wherein chronotype (mid-sleep time on free days corrected for sleep debt on school days) was assessed by the Munich Chronotype Questionnaire. Subsequently, the associations between chronotype, cognitive function, and ROI volumes were evaluated using linear mixed-effects models. Results: Behaviorally, chronotype was negatively associated with vocabulary knowledge, reading skills, and episodic memory performance. Based on these associations, the ROI analysis focused on language-related and episodic memory-related areas revealed a negative association between chronotype and left precentral gyrus and right posterior cingulate cortex volumes. Furthermore, the precentral gyrus volume was positively associated with vocabulary knowledge and reading skills, while the posterior cingulate cortex volume was positively associated with episodic memory performance. Discussion: These results suggest that children with late chronotype have lower language comprehension and episodic memory and smaller brain volumes in the left precentral gyrus and right posterior cingulate cortex associated with these cognitive functions.

Topical application of daphnetin hydrogel for traumatic brain injury.

Background: Traumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the in vivo bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact. Methods: Tripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal in vivo imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA. Results: The efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both in vitro and in vivo tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function. Conclusion: The use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.

Eight-and-a-Half Syndrome Secondary to Acute Brainstem Infarction.

Eight-and-a-half syndrome is a rare neuro-ophthalmologic condition, which is characterized by ipsilateral horizontal gaze palsy, internuclear ophthalmoplegia (INO), and ipsilateral lower motor neuron facial palsy. We report a case of eight-and-a-half syndrome secondary to acute brainstem infarction. A 55-year-old gentleman with underlying diabetes mellitus and hypertension presented with a sudden onset of double vision in the right lateral gaze for one day. On examination, there was a limitation in the left eye horizontal eye movement with limited right eye adduction. Further neurological examination revealed left lower motor neuron facial nerve palsy. Magnetic resonance imaging (MRI) of the brain showed an acute infarct involving the left side of the thalamus extending to the left side of the midbrain, pons, and medulla. He was diagnosed with eight-and-a-half syndrome secondary to acute brainstem infarction. The patient was referred to the neuromedical team, where he was treated with anti-platelet medications. He showed gradual improvement on follow-up and had complete resolution of ophthalmoplegia after three months. There was only minimal residual facial nerve weakness. Eight-and-a-half syndrome has a localizing value to the dorsal tegmentum of the pons. It requires thorough neurological examination and imaging studies for accurate diagnosis and management. This case highlights the potential for a significant recovery in patients with eight-and-a-half syndrome when timely and appropriate treatment is administered.

Biomimetic design and integrated biofabrication of an in-vitro three-dimensional multi-scale multilayer cortical model.

The lack of accurate and reliable in vitro brain models hinders the development of brain science and research on brain diseases. Owing to the complex structure of the brain tissue and its highly nonlinear characteristics, the construction of brain-like in vitro tissue models remains one of the most challenging research fields in the construction of living tissues. This study proposes a multi-scale design of a brain-like model with a biomimetic cortical structure, which includes the macroscopic structural features of six layers of different cellular components, as well as micrometer-scale continuous fiber structures running through all layers vertically. To achieve integrated biomanufacturing of such a complex multi-scale brain-like model, a multi-material composite printing/culturing integrated bioprinting platform was developed in-house by integrating cell-laden hydrogel ink direct writing printing and electrohydrodynamic fiber 3D printing technologies. Through integrated bioprinting, multi-scale models with different cellular components and fiber structural parameters were prepared to study the effects of macroscopic and microscopic structural features on the directionality of neural cells, as well as the interaction between glial cells and neurons within the tissue model in a three-dimensional manner. The results revealed that the manufactured in vitro biomimetic cortical model achieved morphological connections between the layers of neurons, reflecting the structure and cellular morphology of the natural cortex. Micrometer-scale (10 µm) cross-layer fibers effectively guided and controlled the extension length and direction of the neurites of surrounding neural cells but had no significant effect on the migration of neurons. In contrast, glial cells significantly promoted the migration of surrounding PC12 cells towards the glial layer but did not contribute to the extension of neurites. This study provides a basis for the design and manufacture of accurate brain-like models for the functionalization of neuronal tissues.

Molecular hydrogen supplementation in mice ameliorates lipopolysaccharide-induced loss of interest.

Aim: The objective of this study was to evaluate the potential of hydrogen in preventing and treating psychiatric symptoms, particularly depressed mood and loss of interest, and to explore its underlying mechanisms. A mouse model exhibiting inflammation-derived depressive symptoms was used for the investigation. Methods: Institute of Cancer Research mice were subjected to a 7-day intervention of either 30% hydrogen or 40 g per day of air via jelly intake. On the final day, lipopolysaccharide (LPS) was intraperitoneally administered at 5 mg/kg to induce inflammation-related depressive symptoms. Behavioral and biochemical assessments were conducted 24 h post-LPS administration. Results: Following LPS administration, a decrease in spontaneous behavior was observed; however, this effect was mitigated in the group treated with hydrogen. The social interaction test revealed a significant reduction in interactions with unfamiliar mice in the LPS-treated group, whereas the hydrogen-treated group exhibited no such decrease. No significant changes were noted in the forced-swim test for either group. Additionally, the administration of LPS in the hydrogen group did not result in a decrease in zonula occludens-1, a biochemical marker associated with barrier function at the cerebrovascular barrier and expressed in tight junctions. Conclusion: Hydrogen administration demonstrated a preventive effect against the LPS-induced loss of interest, suggesting a potential role in symptom prevention. However, it did not exhibit a suppressive effect on depressive symptoms in this particular model. These findings highlight the nuanced impact of hydrogen in the context of inflammation-induced psychiatric symptoms, indicating potential avenues for further exploration and research.