Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

LC-MS/MS Quantification of Endocannabinoids in Tissues.

Endocannabinoids (ECBs) are lipid-derived endogenous molecules with important physiological roles such as regulation of energy balance, immunity, or neural development. Quantitation of ECBs helps better understand their physiological role and modulation of biological processes. This chapter presents the simultaneous quantification of 14 ECBs and related molecules in the brain, liver, and muscle, as well as white and brown adipose tissue using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dynamic range of the method has been tuned to cover the endogenous concentrations of these analytes given the fact that they are endogenously present at different orders of magnitude. Specifically, three groups are established: 0.5-5000 ng/mL for 2-oleoyl- and 2-linoleoylglycerol and arachidonic acid, 0.05-500 ng/mL for 2-arachidonoylglycerol, and 0.0005-0.5 ng/mL for anandamide, palmitoyl-, palmitoleoyl-, stearoyl-, oleoyl-, linoleoyl-, alpha-linolenoyl-, dihomo-gamma-linolenoyl-, docosahexaenoyl-, and pentadecanoylethanolamide.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Application of electroencephalogram (EEG) in the study of the influence of different contents of alcohol and Baijiu on brain perception.

Alcoholic beverages flavour is complex and unique with different alcohol content, and the application of flavour perception could improve the objectivity of flavour evaluation. This study utilized electroencephalogram (EEG) to assess brain reactions to alcohol percentages (5 %-53 %) and Baijiu's complex flavours. The findings demonstrate the brain's proficiency in discerning between alcohol concentrations, evidenced by increasing physiological signal strength in tandem with alcohol content. When contrasted with alcohol solutions of equivalent concentrations, Baijiu prompts a more significant activation of brain signals, underscoring EEG's capability to detect subtleties due to flavour complexity. Additionally, the study reveals notable correlations, with δ and α wave intensities escalating in response to alcohol stimulation, coupled with substantial activation in the frontal, parietal, and right temporal regions. These insights verify the efficacy of EEG in charting the brain's engagement with alcoholic flavours, setting the stage for more detailed exploration into the neural encoding of these sensory experiences.

Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation.

Calcium Imaging in Brain Tissue Slices.

Calcium imaging is a method that was first developed in the mid-1970s yet kept developing until current days to allow accurate measurement of free calcium ions in tissues. This widely used method has provided significant advances to our understanding of cellular signal transduction, including the discovery of subcellular compartmentalization of neurons and astrocytes, the identification of multiple signaling pathways, and mapping the functional connectivity between astrocytes and neuronal networks. Here we describe a method for the loading and imaging of cell-permeable AM ester calcium-sensitive dyes for the in vitro measurement of free intracellular Ca2+ ions in acute brain slices.

Two-Photon Microscopy to Measure Calcium Signaling in the Living Brain.

Two-photon microscopy enables imaging of calcium signaling at cellular or subcellular resolution up to hundreds of microns deep in the living brain. Changes in the brightness of fluorescent calcium indicators provide a readout of calcium levels over time, affording information about neuronal activity and/or calcium-dependent subcellular signaling. Here, we describe a protocol for repeated two-photon imaging of calcium signals in mice expressing a genetically encoded calcium indicator that have been implanted with a chronic cranial window.

Return to play following craniotomy for non-traumatic brain lesions.

Objective: Return to play (RTP) decisions after cranial surgery are important to patients. Most published data relate to RTP following sports-related brain injury. This study investigated factors that influence neurosurgical RTP decision-making following craniotomy for non-traumatic brain lesions. Methods: A patient scenario-based survey was distributed to U.S. and Europe-based neurosurgeons via the American Association of Neurological Surgeons/Congress of Neurological Surgeons Tumor Section and the European Association of Neuro-Oncology. From one core patient scenario, 5 further scenarios were developed involving patients of varying age, sport preference, tumor pathology, and craniotomy approach. Respondents provided RTP recommendations and factors important in forming these recommendations. Results: Forty-one responses were received; Europe (48%), U.S. (37%). The most commonly cited factors influencing RTP decision-making across scenarios were symptomatic recovery (85.4%), resolution of blood and/or air on imaging (43.4%), and patient demand (31.7%). The sports with the longest average RTP timeline were boxing (10.3 months), rugby (8.7 months), and American football (8.5 months) in the core patient scenario. Twenty-nine percent of neurosurgeons requested neuroimaging before determining RTP recommendations in this scenario, more commonly in America than Europe (46.7% and 5.0% respectively, p = .006). Conclusions: Although limited by sample size, the data provides a foundation to support development of a systematic approach to RTP decision-making following craniotomy for brain lesions of non-traumatic etiology. Future work to develop consensus guidelines will benefit from objective data about outcomes, particularly in relation to repeat imaging prior to RTP.

Deceased Donor Program in India: Listing and Allocation Practices and the Legal Process With Respect to Liver Transplantation.

India is the country with the third largest transplantation activity in the world but has one of the lowest deceased donation rates. The Transplantation of Human Organs Act was first enacted as law 29 years ago, its implementation has been non-uniform and growth in deceased donation has been slow and heterogenous. This review discusses the concept of brain death, ethics of deceased donation and organ allocation, Indian legislation in this area and the regulatory structure of the National Organ transplantation program. We also discuss current status of deceased donation and deceased donor liver transplantation in the country, identify variation in liver allocation policies across Indian states and identify areas of need and potential solutions.

Dietary sn-2 palmitate influences cognitive behavior by increasing the transport of liver-produced lysophosphatidylcholine VLCPUFAs to the brain.

Investigations indicated that sn-2 palmitate have positive effects on brain development, although its mechanism remains largely unexamined. This research delved into how a diet abundant in sn-2 palmitate influenced the cognitive behavior of mice and elucidated the associated mechanisms using metabolomics and lipidomics. The study demonstrated that dietary sn-2 palmitate led to improved working memory and cognition in mice, as well as an increase in brain BDNF concentration when compared to those fed blend vegetable oil (BVO). This was because sn-2 palmitate feeding promoted the synthesis of very long-chain fatty acids (VLCPUFAs) for the lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) in the liver. This led to more efficient delivery of VLCPUFAs to the brain, as indicated by elevated concentration of LPC/LPE-VLCPUFAs in the liver and heightened expression of the major facilitator superfamily domain containing 2a (MFSD2A). In essence, this paper offered a potential mechanism by which sn-2 palmitate enhanced mouse neurodevelopment.

Sturge weber syndrome: A case report.

This report presents a 14-year-old male with seizures and facial port-wine stains, who upon further evaluation was found to have SWS. Early diagnosis and consistent treatment of Sturge-Weber syndrome in children are essential to prevent seizures and improve quality of life. Anti-seizure medications play a crucial role in preventing and controlling seizures.

Traditional Chinese medicine for functional gastrointestinal disorders and inflammatory bowel disease: narrative review of the evidence and potential mechanisms involving the brain-gut axis.

Functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) are common clinical disorders characterized by recurrent diarrhea and abdominal pain. Although their pathogenesis has not been fully clarified, disruptions in intestinal motility and immune function are widely accepted as contributing factors to both conditions, and the brain-gut axis plays a key role in these processes. Traditional Chinese Medicine (TCM) employs a holistic approach to treatment, considers spleen and stomach impairments and liver abnormality the main pathogenesis of these two diseases, and offers a unique therapeutic strategy that targets these interconnected pathways. Clinical evidence shows the great potential of TCM in treating FGIDs and IBD. This study presents a systematic description of the pathological mechanisms of FGIDs and IBD in the context of the brain-gut axis, discusses clinical and preclinical studies on TCM and acupuncture for the treatment of these diseases, and summarizes TCM targets and pathways for the treatment of FGIDs and IBD, integrating ancient wisdom with contemporary biomedical insights. The alleviating effects of TCM on FGID and IBD symptoms are mainly mediated through the modulation of intestinal immunity and inflammation, sensory transmission, neuroendocrine-immune network, and microbiota and their metabolism through brain-gut axis mechanisms. TCM may be a promising treatment option in controlling FGIDs and IBD; however, further high-quality research is required. This review provides a reference for an in-depth exploration of the interventional effects and mechanisms of TCM in FGIDs and IBD, underscoring TCM's potential to recalibrate the dysregulated brain-gut axis in FGIDs and IBD.

Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology. Methods: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD. Results: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including ß-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance. Conclusion: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.

Brain-machine convergent evolution: Why finding parallels between brain and artificial systems is informative.

Central nervous system neurons manifest a rich diversity of selectivity profiles-whose precise role is still poorly understood. Following the striking success of artificial networks, a major debate has emerged concerning their usefulness in explaining neuronal properties. Here we propose that finding parallels between artificial and neuronal networks is informative precisely because these systems are so different from each other. Our argument is based on an extension of the concept of convergent evolution-well established in biology-to the domain of artificial systems. Applying this concept to different areas and levels of the cortical hierarchy can be a powerful tool for elucidating the functional role of well-known cortical selectivities. Importantly, we further demonstrate that such parallels can uncover novel functionalities by showing that grid cells in the entorhinal cortex can be modeled to function as a set of basis functions in a lossy representation such as the well-known JPEG compression. Thus, contrary to common intuition, here we illustrate that finding parallels with artificial systems provides novel and informative insights, particularly in those cases that are far removed from realistic brain biology.

Cerebral Echinococcosis Mimicking a Brain Tumour in Rural Southwest Nigeria.

Echinococcosis is a zoonosis caused by tapeworms of the genus Echinococcus. Cerebral echinococcosis (CE) poses a significant public health challenge due to its neglected status. It is endemic in Central Asia, Africa and parts of South America, with prevalence estimated to be 1.18-3 per 100,000 population in Iran. We report the case of a 45-year-old male who presented with seizure disorders and was evaluated and treated for a neoplasm, with complete excision of the lesion. Pathologic examination revealed the characteristic echinococcal (hydatid) cyst. The patient recovered fully. As CE is a great imitator of several other conditions in endemic areas, a high index of suspicion must be maintained in endemic countries.

L'échinococcose est une zoonose provoquée par des ténias du genre Echinococcocus. L'échinococcose cérébrale (EC) pose un défi de santé publique important en raison de son statut négligé. Elle est endémique en Asie centrale, en Afrique et dans certaines parties de l'Amérique du Sud, avec une prévalence estimée entre 1,18 et 3 pour 100 000 habitants en Iran. Nous rapportons le cas d'un homme de 45 ans qui a présenté des troubles épileptiques et a été évalué et traité pour une tumeur, avec excision complète de la lésion. L'examen pathologique a révélé le kyste échinococcique (hydatique) caractéristique. Le patient s'est complètement rétabli. Comme l'EC est un grand imitateur de plusieurs autres conditions dans les zones d'endémie, un indice de suspicion élevé doit être maintenu dans les pays d'endémie. MOTS CLÉS: Tumeur cérébrale, rapport de cas, échinococcose cérébrale, sud-ouest du Nigeria.

Multimodal brain tumor segmentation and classification from MRI scans based on optimized DeepLabV3+ and interpreted networks information fusion empowered with explainable AI.

Explainable artificial intelligence (XAI) aims to offer machine learning (ML) methods that enable people to comprehend, properly trust, and create more explainable models. In medical imaging, XAI has been adopted to interpret deep learning black box models to demonstrate the trustworthiness of machine decisions and predictions. In this work, we proposed a deep learning and explainable AI-based framework for segmenting and classifying brain tumors. The proposed framework consists of two parts. The first part, encoder-decoder-based DeepLabv3+ architecture, is implemented with Bayesian Optimization (BO) based hyperparameter initialization. The different scales are performed, and features are extracted through the Atrous Spatial Pyramid Pooling (ASPP) technique. The extracted features are passed to the output layer for tumor segmentation. In the second part of the proposed framework, two customized models have been proposed named Inverted Residual Bottleneck 96 layers (IRB-96) and Inverted Residual Bottleneck Self-Attention (IRB-Self). Both models are trained on the selected brain tumor datasets and extracted features from the global average pooling and self-attention layers. Features are fused using a serial approach, and classification is performed. The BO-based hyperparameters optimization of the neural network classifiers is performed and the classification results have been optimized. An XAI method named LIME is implemented to check the interpretability of the proposed models. The experimental process of the proposed framework was performed on the Figshare dataset, and an average segmentation accuracy of 92.68 % and classification accuracy of 95.42 % were obtained, respectively. Compared with state-of-the-art techniques, the proposed framework shows improved accuracy.

Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.

The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes and astrocytes, and stem cell-derived neurons and astrocytes harboring Familial AD (FAD) mutations. Over an extended co-culture period, the model demonstrates increased BBB permeability, dysregulation of key endothelial and pericyte markers, and morphological alterations mirroring AD pathologies. The model enables visualization of amyloid-beta (Aß) accumulation in both neuronal and vascular compartments. This model may serve as a versatile tool for neuroscience research and drug development to provide insights into the dynamic relationship between vascular dysfunction and AD pathogenesis.

Nivolumab plus ipilimumab with chemotherapy for non-small cell lung cancer with untreated brain metastases: A multicenter single-arm phase 2 trial (NIke, LOGiK 2004).

BACKGROUND: The effect of dual immunotherapy combined with platinum-based chemotherapy on untreated brain metastases derived from non-small cell lung cancer (NSCLC) has remained unclear. METHODS: This multicenter single-arm phase 2 study enrolled patients with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥ 5 mm in size that had not been previously treated. Patients received nivolumab plus ipilimumab combined with platinum-doublet chemotherapy (two cycles), followed by nivolumab-ipilimumab alone. The primary endpoint of the study was intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥ 5 mm as target lesions. RESULTS: A total of 30 patients from 18 institutions was enrolled in this study. The median age was 66.5 years (range, 47-83 years), and 26 patients (87 %) had a non-squamous cell carcinoma histology. The median size of all target brain lesions was 8.4 mm, with a range of 5-39 mm. The intracranial response rate assessed by modified RECIST was 50.0 % (95 % CI, 33.2-66.8 %), with the rate of complete response being 20.0 %, and the study met its primary endpoint. The systemic response rate was 53.3 % (95 % CI, 36.1-69.8 %), and responses for intracranial and extracranial lesions were generally consistent. The median intracranial progression-free survival was 8.1 months, and both the median intracranial duration of response and time to brain radiotherapy were not reached. CONCLUSION: Nivolumab plus ipilimumab combined with platinum-based chemotherapy showed promising intracranial activity in NSCLC patients with untreated brain metastases. TRIAL REGISTRATION: jRCT071210019.

Current status and influencing factors of fear disease progression in Chinese primary brain tumor patients: A mixed methods study.

OBJECTIVE: In this study, we investigated the fear of disease progression in Chinese PBT patients and examined the correlation between sociodemographic, clinical, and psychological variables of patients with the fear of progression (FoP). Additionally, the study also evaluated the subjective experience of FoP in patients with primary brain tumors (PBT). METHODS: A mixed-methods study was conducted between March 2022 and December 2023, consisting of two phases: a quantitative approach in phase I, and a qualitative approach in phase II. In phase I, 305 patients with PBT filled in several questionnaires. An analysis was performed to identify potential predictors associated with FoP. In phase II, semi-structured interviews were conducted with 16 participants whose FoP scores were ≥ 34 in phase I to obtain information on their personal experiences with FoP. RESULTS: The results of the quantitative study showed that 192 (63 %) patients experienced high levels of FoP. The mean score of fear of progression was (34.02±6.78). Young age, high disease uncertainty, low social support, high negative coping and low positive coping are important factors affecting FoP in PBT patients. Qualitative research focused on three themes: triggers, coping styles, and the help needed. CONCLUSION: Enhanced screening and assessment of FoP is essential to identify dysfunctionin PBT. Meanwhile, the implications of these predictors for enhanced healthcare professional education and patient self-management may help healthcare providers implement relevant interventions promptly and help patients reduce their FoP. However, due to limitations such as sample, reporting bias, and specific mechanisms between predictors and FOPs that have not yet been explored in depth, further exploration is needed in the future.