Brain Research最新文献

{"title":"Multimodal response-predictor analysis for three non-invasive brain stimulation protocols.","authors":"Jean-Marc Therrien-Blanchet, Marie Chantal Ferland, Meriem Badri, Marie-Andrée Rousseau, Amira Merabtine, Emelie Boucher, Lydia Helena Hofmann, Arnaud Boré, Maxime Descoteaux, Jean-François Lepage, Hugo Théoret","doi":"10.1016/j.brainres.2024.149372","DOIUrl":"10.1016/j.brainres.2024.149372","url":null,"abstract":"<p><p>Non-invasive brain stimulation (NIBS) methods such as paired associative stimulation (PAS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are used to modulate cortical excitability and reduce symptoms in a variety of psychiatric disorders. Recent studies have shown significant inter-individual variability in the physiological response to these techniques when they are applied over the hand representation of primary motor cortex (M1_hand). The goal of the present study was to identify neurophysiological, neuroanatomical, and neurochemical baseline characteristics that may predict response to commonly used NIBS protocols using data from a previously published study (Therrien-Blanchet et al., 2023). To this end, PAS, anodal tDCS, and 20-Hz tACS were administered to healthy participants in a repeated measures design. Pre/Post differences in transcranial magnetic stimulation-induced input-output curves were used to quantify changes in corticospinal excitability. Primary predictors were late I-wave latency, cortical thickness (CT) of M1_hand, and fractional anisotropy of the corticospinal tract (CST_hand) originating from M1_hand. Secondary exploratory analysis was performed with CT in areas outside motor cortex, diffusion MRI (dMRI) metrics of the CST_hand, magnetic resonance spectroscopy measurements of GABA, glutamate, and n-acetyl aspartate of M1_hand, baseline corticospinal excitability, and cranial circumference. Multiple regression analysis showed that none of the primary variables predicted intervention outcome for any of the NIBS protocols. Exploratory analysis revealed no significant correlation between predictor variables and PAS outcome. tDCS and tACS were significantly correlated with some baseline measures. These data suggest that modulation of cortical excitability following several NIBS protocols may not be easily predicted by baseline characteristics, underscoring the need for a better understanding of their mechanism of action. Significant exploratory associations need to be confirmed in larger samples and confirmatory designs.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149372"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPNMB attenuates neuroinflammation and improves ischemic stroke via modulation of PI3K/Akt and p38 MAPK signaling pathways.","authors":"Yukun Ping, Jiyu Li, Linlin Xie, Jie Zhao, Xuyu Chen, Danni Chen, Yamin Wang, Chao Jiang, Xiaobo Li","doi":"10.1016/j.brainres.2024.149381","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149381","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a leading cause of disability and mortality worldwide, with limited effective treatments. Neuroinflammation plays a crucial role in the progression of ischemic brain injury. Glycoprotein nonmetastatic melanoma protein B (GPNMB) has emerged as a potential regulator of inflammation, but its role and underlying mechanisms in ischemic stroke remain largely unknown.</p><p><strong>Methods: </strong>We investigated the expression profile, functional significance, and molecular pathways of GPNMB in ischemic stroke using a mouse model of middle cerebral artery occlusion (MCAO), transcriptome sequencing, and human serum samples. The effects of GPNMB knockdown on stroke outcomes, neuroinflammation, and neuronal damage were assessed in vivo. Bioinformatic analyses and experimental validation were performed to identify the downstream signaling pathways of GPNMB.</p><p><strong>Results: </strong>GPNMB was highly upregulated in the ischemic brain, with its expression peaking at 3-7 days post-MCAO. Serum GPNMB levels were elevated in ischemic stroke patients and correlated with stroke severity. GPNMB knockdown exacerbated stroke outcomes, neuroinflammation, and neuronal damage. Mechanistically, GPNMB positively modulated the PI3K/Akt/GSK3β pathway while negatively regulating p38 MAPK, JNK, and ERK activation. GPNMB knockdown enhanced the expression of NF-κB, a master transcriptional regulator of inflammation.</p><p><strong>Conclusion: </strong>GPNMB is highly upregulated in the ischemic brain and confers neuroprotection against ischemic injury by modulating neuroinflammation via the PI3K/Akt and p38 MAPK signaling pathways.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1849 ","pages":"149381"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of gut dysbiosis in drug-resistant epilepsy: Pathogenesis and available therapeutic strategies.","authors":"Nidhi Khedpande, Kalyani Barve","doi":"10.1016/j.brainres.2024.149385","DOIUrl":"10.1016/j.brainres.2024.149385","url":null,"abstract":"<p><p>Over 70 million people worldwide suffer from epilepsy, a persistent brain disorder. Although there are more than 20 antiseizure drugs available for the symptomatic treatment of epilepsy, about one-third of patients with epilepsy experience seizures that show resistance to pharmacotherapy. Since patients with drug-resistant epilepsy are more prone to physical injuries, psychosocial dysfunction, early death, and deteriorated life quality, the development of safer and more effective treatments is a crucial clinical need. The gut-brain axis and microbiome research advances have provided new insights into the pathophysiology of epilepsy, the resistance to anti-seizure medicine, and potential treatment targets. Inflammation, disturbance of the blood-brain barrier, and altered neurotransmitters are key pathways linked to gut dysbiosis. The characterization of microbial species and functional pathways has advanced thanks to metagenomic sequencing and high-throughput analysis. In this review, we elaborate on the gut-mediated molecular pathways involved in drug-resistant epilepsy, the gut- modulatory therapeutic options, and their combination with antiseizure medications for drug-resistant epilepsy.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149385"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Santiago Ramón y Cajal: Artistic legacy in Science, 90 years later.","authors":"Larissa Junkes, Antonio E Nardi","doi":"10.1016/j.brainres.2024.149384","DOIUrl":"10.1016/j.brainres.2024.149384","url":null,"abstract":"<p><p>Ninety years after his death in 1934, the artistic beauty of the innovative brain images created by physician and histologist Santiago Ramón y Cajal, as well as his revolutionary neuroanatomical theory, remains relevant today. As a scientist who isolated brain nerve cells, he visualized them as physically distinct entities, answering one of the most crucial questions of his time. Prior to his work, the prevailing belief was in the reticular theory, which suggested that nervous tissue was continuous and formed a network of interconnected cells. His anatomical studies helped establish the foundations of modern neuroscience. Cajal, who worked in solitude for many years, embodied one of the most important virtues of a scientist in his life: perseverance.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149384"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine protease inhibitor AEBSF(4-(2-aminoethyl)-benzenesulfonyl fluoride) decreased ischemic brain injury through inhibiting endoplasmic reticulum stress, oxidative stress, and autophagy in rats.","authors":"Qi An, Yuequan Zhu, Wenjuan Shi, Wei Li, Xueqi Yang, Minqi Huang, Yakun Li, Yongmei Zhao","doi":"10.1016/j.brainres.2024.149382","DOIUrl":"10.1016/j.brainres.2024.149382","url":null,"abstract":"<p><p>4-(2-Aminoethyl)-benzenesulfonyl fluoride (AEBSF) is a serine protease inhibitor that may alleviate endoplasmic reticulum (ER) stress, a significant contributing factor to cerebral ischemia/reperfusion injury. The molecular crosstalk between ER stress, oxidative stress and autophagy represents a vicious cycle that can be pharmacologically targeted to minimize neuronal death after acute injuries to the central nervous system. However, the neuroprotective effects of AEBSF in the context of cerebral ischemia/reperfusion injury remain unknown. In this study,we reported the neuroprotective effect of AEBSF against cerebral ischemia/reperfusion injury and explored the mechanisms involved, particularly its role in reducing ER stress, oxidative stress and autophagy. Rats were pretreated with AEBSF or a vehicle before a 90 min middle cerebral artery occlusion (MCAO) followed by 24 h of reperfusion. Our results demonstrate that AEBSF treatment reduced infarct volume and improved neurological function compared to vehicle treated rats after 24 h of reperfusion. Furthermore,AEBSF treatment decreased the expression of caspase-3, suggesting a decrease in neuronal apoptosis. Additionally, AEBSF treatment lowered levels of key ER stress biomarkers, including glucose-regulated protein 78 (GRP78), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), and CCAAT-enhancer-binding protein homologous protein (CHOP), while the levels of inositol-requiring enzyme 1α (IRE1α) remained unchanged. AEBSF also decreased the oxidative stress biomarker neuronal nitric oxide synthase (nNOS) and its related molecule pro-MMP-9. Importantly, treatment with AEBSF reversed the trends of autophagy biomarker LC3B II/α-tubulin, Beclin1, and SQSTM1 at 24 h after reperfusion. In conclusion, AEBSF significantly mitigates ischemic brain damage and promotes neurological recovery by inhibiting ER stress, oxidative stress, and autophagy, highlighting its potential as a therapeutic option for ischemic stroke.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149382"},"PeriodicalIF":2.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of delta opioid receptor inhibition of parallel fibers-purkinje cell synaptic transmission in the mouse cerebellar cortex.","authors":"Lu Zhang, Dan Wang, Shuang Shi, Shuang Wu, Zhi Li, Jun Nan, Yan Lan","doi":"10.1016/j.brainres.2024.149374","DOIUrl":"10.1016/j.brainres.2024.149374","url":null,"abstract":"<p><p>Delta opioid receptors (DORs) are widely expressed throughout the central nervous system, including the cerebellum, where they play a regulatory role in neurogenesis. In the cerebellar cortex, Purkinje cells (PCs), the sole output neurons, receive glutamatergic synaptic input from parallel fibers (PFs)-the axonal extensions of granule cells-forming PF-PC synapses. However, the precise distribution of DORs within these synapses and their impact on synaptic transmission remain unclear. In this study, we utilized whole-cell patch-clamp recordings and neuropharmacological approaches to explore the effects of DORs activation on PF-PC synaptic transmission in the mouse cerebellar cortex and to elucidate the underlying mechanisms. We found that the selective DORs agonist DPDPE significantly reduced the amplitude and area under the curve (AUC) of PF-PC evoked excitatory postsynaptic currents (eEPSCs), accompanied by an increase in the paired-pulse ratio (PPR). This inhibitory effect was blocked by the DORs antagonist Naltrindole. Additionally, DPDPE decreased the frequency of PF-PC miniature excitatory postsynaptic currents (mEPSCs) without affecting their amplitude, indicating a presynaptic site of action. When the protein kinase A (PKA) inhibitor PKI was added to the internal solution of the recording electrode, it did not alter the DPDPE-induced suppression of PF-PC mEPSC frequency. However, this suppression was reversed by KT5720, a cell-permeable PKA-specific inhibitor. These findings suggest that DPDPE inhibits PF-PC synaptic transmission through the preferential activation of presynaptic DORs, with this process being dependent on the cyclic adenosine monophosphate (cAMP)-PKA signaling pathway.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149374"},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Machine learning classification framework using fused fractal property feature vectors for Alzheimer's disease diagnosis.","authors":"Sixiang Sun, Can Cui, Yuanyuan Li, Yingjian Meng, Wenxiang Pan, Dongyan Li","doi":"10.1016/j.brainres.2024.149373","DOIUrl":"https://doi.org/10.1016/j.brainres.2024.149373","url":null,"abstract":"<p><p>Alzheimer's disease (AD) profoundly affects brain tissue and network structures. Analyzing the topological properties of these networks helps to understand the progression of the disease. Most studies focus on single-scale brain networks, but few address multiscale brain networks. In this study, the renormalization group approach was applied to rescale the gray matter brain networks of AD patients and cognitively normal (CN) into three scales: the original, once-renormalized, and twice-renormalized networks. Based on the fractal property of these networks at different scales, a novel framework for classifying Alzheimer's disease using fractal and renormalization group was proposed. We integrated the fractal metrics across different scales to create fused feature vectors, which served as inputs for the classification framework aimed at diagnosing Alzheimer's disease. The experimental result indicates that the original and once-renormalized networks of both CN and AD exhibit the fractal property. The classification framework performed best when using the fused feature vector, including the average connection ratio of the original and once-renormalized networks. Using the fused feature vector of the average connection ratio, the One-Dimensional Convolution Neural Network model achieved an accuracy of 92.59% and an F1 score of 91.19%. This marks an improvement of approximately 10% in accuracy and 5% in F1 score compared to results using feature fusion of the average degree, average path length, and clustering coefficient.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149373"},"PeriodicalIF":2.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered gut microbiome profiles in epileptic children are associated with spectrum of anti-seizure medication responsiveness.","authors":"Rattakarn Yuwattana, Kanokphong Suparan, Sasiwan Kerdphoo, Busarin Arunsak, Chinnuwat Sanguansermsri, Kamornwan Katanyuwong, Nipon Chattipakorn, Natrujee Wiwattanadittakul, Siriporn C Chattipakorn","doi":"10.1016/j.brainres.2024.149367","DOIUrl":"10.1016/j.brainres.2024.149367","url":null,"abstract":"<p><p>Gut microbiota plays a role in epilepsy. However, current knowledge of how gut dysbiosis is associated with a response to anti-seizure medications (ASMs) in epileptic children is still limited. We aimed to characterize the gut microbiota profiles in epileptic children based on response to ASMs. Eighty-six children aged 3-18 years old with a regular oral diet were enrolled onto the study and divided into three groups in accordance with ILAE definitions: 26 healthy controls, 31 drug-sensitive epilepsy (DSE) patients, and 29 drug-resistant epilepsy (DRE) patients. Based on ASM responsiveness, defined as a reduction in seizure frequency of at least 75 % over one year, DRE individuals were subclassified into 13 drug responsive (DRE-DR) and 16 drug non-responsive (DRE-DNR) patients. Feces were collected at the time of enrollment for gut microbiota analysis using 16S rRNA sequencing. Epileptic patients exhibited distinctive gut dysbiotic profiles. Differential abundance investigation revealed that CAG-56 was significantly increased in epileptic patients compared to controls. Saccharimonadales and Peptoclostridium significantly increased in the DSE group, compared to the DRE group. Vibrionaceae, especially Grimontia, Rhodobacteraceae, and Enterobacter were significantly abundant in the DRE-DNR group, followed by abundance in the DRE-DR and DSE groups. Outcomes from PICRUSt2 analysis predicted that epileptic patients, especially those in the DRE group, had increased metabolic pathways responsible for vanillin and taurine degradation, compared to controls. These findings suggest that gut dysbiosis could play roles in epileptogenesis and ASM resistance. Notably, the identified gut microbes could serve as predictive biomarkers for the DRE condition.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149367"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural alteration of hippocampal subfields in type 2 diabetes mellitus patients with dyslipidemia.","authors":"Chen Yang, Huiyan Zhang, Jing Tian, Zhoule Li, Ruifang Liu, Gang Huang, Lianping Zhao","doi":"10.1016/j.brainres.2024.149368","DOIUrl":"10.1016/j.brainres.2024.149368","url":null,"abstract":"<p><strong>Objective: </strong>To explore alterations in hippocampal subfield volumes in type 2 diabetes mellitus (T2DM) patients with dyslipidemia using hippocampal subfield segmentation.</p><p><strong>Methods: </strong>A total of 99 T2DM patients were prospectively recruited and divided into two groups based on the presence or absence of dyslipidemia: the T2DM dyslipidemia group and the T2DM normal lipidemia group. Additionally, 57 healthy volunteers were recruited as the healthy control (HC) group. General clinical data and cognitive psychological scale scores were collected. Subgroup analyses of T2DM patients were conducted based on the presence or absence of mild cognitive impairment (MCI). Hippocampal subfield volumes were analyzed using a general linear model with post-hoc Bonferroni correction. Significant differential hippocampal subfields were further analyzed in subgroups using the general linear model with post-hoc Bonferroni tests. Partial correlation analyses were performed to assess correlations between subfield-specific volumes and lipid and glucose metabolism indicators, as well as cognitive psychological scale scores. P-values from partial correlation analyses were corrected using the false discovery rate (FDR).</p><p><strong>Results: </strong>Volumes of the bilateral hippocampal tail, left presubiculum_body, and right subiculum_body were significantly reduced in the T2DM dyslipidemia group compared to both the HC group and the T2DM normal lipidemia group. Post-hoc analyses revealed that the T2DM dyslipidemia group had the smallest hippocampal subfield volumes. Further subgroup analysis showed that T2DM dyslipidemia patients with MCI exhibited the most pronounced volume reductions in the bilateral hippocampal tail and right subiculum_body. After FDR correction, partial correlation analysis indicated that, in the T2DM dyslipidemia group, the left hippocampal tail volume was positively correlated with the Montreal Cognitive Assessment score. In the T2DM dyslipidemia without MCI group, the volume of the right subiculum_body was negatively correlated with fasting insulin levels and the insulin resistance index, but positively correlated with total cholesterol and low-density lipoprotein cholesterol levels. In T2DM patients with normal lipidemia without MCI, the volume of the right subiculum_body was positively correlated with TC levels.</p><p><strong>Conclusion: </strong>T2DM patients with dyslipidemia, especially those with MCI, exhibit significant atrophy in hippocampal subfield volumes, with correlations observed between lipid levels and hippocampal subfield volume changes. These findings suggest that lipid alterations may play an essential role in hippocampal structural abnormalities and cognitive impairment in T2DM patients. This study provides new insights into the neuropathophysiological mechanisms underlying brain alterations and cognitive decline in T2DM.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149368"},"PeriodicalIF":2.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of hyperglycemia on neuronal network function in an in vitro model of the ischemic penumbra.","authors":"C J B A Kersten, T H Vrielink, H M den Hertog, J Hofmeijer, J le Feber","doi":"10.1016/j.brainres.2024.149370","DOIUrl":"10.1016/j.brainres.2024.149370","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperglycemia is common in acute ischemic stroke, and associated with unfavorable outcome. However, the optimal glucose level is not known and cellular effects of hyperglycemia under hypoxia are largely unclear. We assessed how the extracellular glucose concentration affects cultured neuronal networks under experimental in vitro conditions, to provide a starting point for assessment of mechanisms at the neuronal network and cellular levels.</p><p><strong>Methods: </strong>We used in vitro cultured rat neuronal networks on micro-electrode arrays (MEAs) and glass coverslips. Twenty-four hours of controlled hypoxia was induced. We measured neuronal network activity during baseline (normoxia, 6 h), 24 h of hypoxia, and 6 h after reoxygenation, defined as the summed number of action potentials in 1 h bins. Apoptosis was determined intermittently with caspase 3/7 staining and microscopy. We compared groups of networks under glucose concentrations of 5.0 mmol/L, 7.0 mmol/L, 9.0 mmol/L, and 12.0 mmol/L.</p><p><strong>Results: </strong>Overall, during hypoxia, a gradual decrease in neuronal network activity and increase in apoptosis was found. There were faster decrease in activity (p < 0.01) and more apoptosis after 24 h of hypoxia under glucose levels of 12 mmol/L in a single-well MEA set-up (p < 0.05), and more apoptosis in glass coverslips with glucose levels of 12.0 mmol/L in comparison with 5 mmol/L (p = 0.03). These differences were not observed in multi-well MEAs, in which effects of hypoxia were much smaller than in single-well MEAs.</p><p><strong>Conclusion: </strong>Hyperglycemia was associated with a more rapid decrease of neuronal network activity during and more apoptosis after 24 h of hypoxia in cultured neuronal networks. Loss of neuronal activity and apoptosis probably play a role in poorer outcomes of stroke patients under hyperglycemia. Our model provides a starting point for further assessment of pathomechanisms.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149370"},"PeriodicalIF":2.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}